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 »  Abstract
 » Introduction
 » Methodology
 » Results
 » Discussion
 » Conclusion
 »  References
 »  Article Figures
 »  Article Tables

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  Table of Contents  
Year : 2022  |  Volume : 59  |  Issue : 5  |  Page : 19-45

Expert survey on management of prostate cancer in India: Real-world insights into practice patterns

1 Department of Uro-Oncology, P D Hinduja National Hospital, Mumbai, India
2 Director of Surgical Oncology and Uro-Oncology, Max Nanavati Hospital, Mumbai, India
3 Department of Uro-Oncology, Apollo Hospital, Hyderabad, India
4 Department of Uro-Onco Pathology, Tata Memorial Hospital & HBNI, Mumbai, India
5 Department of Uro-Oncology, BL Kapoor Hospital, Delhi, India
6 Department of Uro-Oncology, Narayana Health, Kolkata, India
7 Department of Urology, Bapat Urology Hospital, Mumbai, India
8 Department of Medical Oncology, Prince Aly Khan Hospital, Mumbai, India
9 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India
10 Department of Uro-Oncology, Cancer Institute (WIA), Adyar, Chennai, India
11 Department of Urology, Excel Urology Centre, Mumbai, India
12 Department of Medical Oncology, Apollo Hospital, Chennai, India
13 Department of Urology, Safdarjung Hospital, Delhi, India
14 Department of Nuclear Medicine, Tata Memorial Hospital & HBNI, Mumbai, India
15 Department of Pathology, Apollo Hospital, Mumbai, India
16 Department of Medical Oncology, Mumbai Oncocare Centre, Mumbai, India
17 Department of Medical Oncology, Christian Medical College, Vellore, India
18 Department of Urology, King George Medical University, Lucknow, India
19 Department of Medical Oncology, Tata Memorial Centre, Kolkata, India
20 Department of Surgical Oncology, Oncolife Hospital, Satara, India
21 Department of Uro-Oncology, Max Healthcare, Delhi, India
22 Department of Uro-Oncology, Tata Memorial Hospital & HBNI, Mumbai, India
23 Department of Uro-Oncology, King George Medical University, Lucknow, India
24 Department of Urology, RML Hospital, Delhi, India
25 Department of Uro-Oncology, Breach Candy Hospital, Mumbai, India
26 Department of Uro-Oncology, VSS Hospital, Bhubaneshwar, India
27 Department of Medical Oncology, Tristar Hospital, Surat, India
28 Department of Urology, Jaslok Hospital, Mumbai, India
29 Department of Medical Oncology, Artemis Hospital, Delhi, India
30 Department of Medical Oncology, HCG Hospital, Bangalore, India
31 Department of Uro-Oncology, HCG Hospital, Bangalore, India
32 Department of Radiation Oncology, Tata Memorial Hospital & HBNI, Mumbai, India
33 Department of Uro-Oncology, Ruby Hall Clinic, Pune, India
34 Department of Uro-Oncology, Indo-American Hospital, Hyderabad, India
35 Department of Medical Oncology, CHL Hospital, Indore, India
36 Department of Urology, Institute of Medical Science, Varanasi, India
37 Department of Urology, Nanavati Hospital, Mumbai, India
38 Department of Urology, SGPGI, Lucknow, India
39 Department of Surgical Oncology, Mohan's Medicity Hospital, Madurai, India
40 Department of Urology, Lilavati Hospital, Mumbai, India
41 Department of Uro-Oncology, Sri Shankara Hospital, Bangalore, India
42 Department of Medical Oncology, SL Raheja Hospital, Mumbai, India
43 Department of Uro-Oncology, AINU Hospital, Hyderabad, India
44 Department of Medical Oncology, Apollo Hospital, Hyderabad, India

Date of Submission24-Sep-2021
Date of Decision07-Jan-2022
Date of Acceptance13-Jan-2022
Date of Web Publication24-Mar-2022

Correspondence Address:
Ganesh Bakshi
Department of Uro-Oncology, P D Hinduja National Hospital, Mumbai
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.ijc_1145_21

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 » Abstract 

To gain insights on the diverse practice patterns and treatment pathways for prostate cancer (PC) in India, the Urological Cancer Foundation convened the first Indian survey to discuss all aspects of PC, with the objective of guiding clinicians on optimizing management in PC. A modified Delphi method was used, wherein a multidisciplinary panel of oncologists treating PC across India developed a questionnaire related to screening, diagnosis and management of early, locally advanced and metastatic PC and participated in a web–based survey (WBS) (n = 62). An expert committee meeting (CM) (n = 48, subset from WBS) reviewed the ambiguous questions for better comprehension and reanalyzed the evidence to establish a revote for specific questions. The threshold for strong agreement and agreement was ≥90% and ≥75% agreement, respectively. Sixty-two questions were answered in the WBS; in the CM 31 questions were revoted and 4 questions were added. The panelists selected answers based on their best opinion and closest to their practice strategy, not considering financial constraints and access challenges. Of the 66 questions, strong agreement was reached for 17 questions and agreement was achieved for 22 questions. There were heterogeneous responses for 27 questions indicative of variegated management approaches. This is one of the first Indian survey, documenting the diverse clinical practice patterns in the management of PC in India. It aims to provide guidance in the face of technological advances, resource constraints and sparse high-level evidence..

Keywords: India, prostate cancer, survey

How to cite this article:
Bakshi G, Tongaonkar H, Addla S, Menon S, Pradhan A, Kumar A, Bapat A, Gore A, Joshi A, Raja A, Bradoo A, Ramesh A, Kumar A, Agrawal A, Ambekar A, Joshi A, Singh A, Singh BP, Dabkara D, Khadakban D, Gautam G, Prakash G, Pahwa HS, Goel HK, Kulkarni J, Mishra JJ, Patel K, Pal M, Chibber PJ, Tiwari P, Naik R, Raghunath S K, Krishnatry R, Shimpi R, Sharma R, Taran R, Trivedi S, Nabar S, Surekha S, Kumar S, Sawaimoon SK, Raina S, Narasimha S, Advani S, Ghouse SM, Muddu VK, Maniar V, Venkat V, Murthy V. Expert survey on management of prostate cancer in India: Real-world insights into practice patterns. Indian J Cancer 2022;59, Suppl S1:19-45

How to cite this URL:
Bakshi G, Tongaonkar H, Addla S, Menon S, Pradhan A, Kumar A, Bapat A, Gore A, Joshi A, Raja A, Bradoo A, Ramesh A, Kumar A, Agrawal A, Ambekar A, Joshi A, Singh A, Singh BP, Dabkara D, Khadakban D, Gautam G, Prakash G, Pahwa HS, Goel HK, Kulkarni J, Mishra JJ, Patel K, Pal M, Chibber PJ, Tiwari P, Naik R, Raghunath S K, Krishnatry R, Shimpi R, Sharma R, Taran R, Trivedi S, Nabar S, Surekha S, Kumar S, Sawaimoon SK, Raina S, Narasimha S, Advani S, Ghouse SM, Muddu VK, Maniar V, Venkat V, Murthy V. Expert survey on management of prostate cancer in India: Real-world insights into practice patterns. Indian J Cancer [serial online] 2022 [cited 2022 Oct 1];59, Suppl S1:19-45. Available from:

 » Introduction Top

Prostate cancer (PC) is the sixth leading cause of cancer death among men worldwide, accounting for an estimated 358,989 deaths in 2018.[1] PC accounted for the fifth highest incidence rate among males in India in 2016 (4.8 per 100,000), with a significant increase in age-standardized incidence rate by 29.8% from 1990 to 2016. The premise that the prevalence of PC in India is lower than in the Western world is changing with population-based cancer registries showing a constant and rapid increase.[2] The Indian Council of Medical Research reported an incidence rate of 9–10/100,000 population, higher compared to other countries in Asia/Africa, but lower when compared to the United States (US)/Europe.[3] In addition, developing countries have more patients in advanced stages as compared to the Western world. Despite lower incidence, the survival rate for PC is relatively low (5-year and 10-year survival rate: 61.9% [95% CI: 59.5–64.3] and 36.2% [95% CI: 9.2–63.2], respectively) in Asian countries, compared to Europe and North America (5-year survival rate: 83% and 98%, respectively).[4–6]

The recent increase in the PC incidence in India can be primarily attributed to the increased migration of the rural population to urban areas, changing dietary and lifestyle habits, and increased awareness and easier access to medical facilities in urban areas.[7–9] However, India being a vast country has marked differences in detection practices, access, affordability, and availability of treatment modalities across different regions. The overall low disease awareness, disparate medical care access, late diagnosis, inadequate documentation, and lack of robust PC data in Indian patients make the management of PC difficult.

The landscape of PC management has undergone major shifts in recent years because of evolving modalities of imaging and novel therapies.[10] Although developing countries, including India, adopt Western guidelines for management of PC, there are wide differences in disease demography, practice patterns, availability of medical resources, and expertise, resulting in knowledge gaps with fragmented data. Realizing the unmet need for gaining insights on diverse practice patterns and treatment pathways in India, the Urological Cancer Foundation convened the first Indian survey to discuss all aspects of PC. The objectives were to understand the real-world practice patterns for PC management in India and to guide clinicians on optimizing management, in line with current international guidelines and clinical judgment. Consensus statements are periodically published by the Advanced Prostate Cancer Consensus Conference (APCCC), the latest being 2019.[10] While these statements per force deal with locally advanced and metastatic disease, we aimed to adapt and extend the concept to diagnosis and treatment of localized PC as well.

 » Methodology Top

We followed a three-step process based on the modified Delphi technique [Figure 1] to ensure a validated approach. A multidisciplinary panel of medical oncologist, nuclear medicine specialist, pathologist, radiation oncologist, surgical oncologist, uro oncologist, and urologist treating PC across India identified the most clinically relevant domains of PC diagnosis and management and framed a questionnaire focused on practice patterns and clinical decision challenges. In late November 2019, some of the panelists (n = 62) participated in a web-based survey (WBS) of questions related to screening, diagnosis and management of early, locally advanced and metastatic PC (mPC). Discordance for a few questions occurred, probably because of a diversity in perception and comprehension by the respondents, affecting their choice of answers.
Figure 1: Flowchart illustrating methodology of the Indian survey on prostate cancer

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An expert committee meeting (CM) (n = 48, subset from WBS, December 2019) reviewed and streamlined (if required) ambiguous questions for better comprehension and reanalyzed the evidence basis to establish a revote for specific questions. The re-vote accrued during the CM took precedence and was considered final. The questions were discussed in three moderator-led sessions in a sequence: screening and diagnosis, localized and locally advanced PC (aPC), and mPC. The definitions considered by the panel are summarized in [Supplementary Table 1]; National Comprehensive Cancer Network (NCCN),[11] European Association of Urology (EAU),[12] European Society for Medical Oncology (ESMO),[13] American Urological Association (AUA)/American Society for Radiation Oncology. (ASTRO)/Society of Urologic Oncology (SUO),[14] and National Institute for Health and Care Excellence (NICE) guidelines.[15] The panelists were instructed to select answers based on their best opinion and closest to their practice strategy, not considering financial constraints and access challenges.

Proportions were calculated for all questions; the denominator was the number of panel members who voted for a particular question, excluding those who voted “unqualified to answer” or “cannot decide” or those who “abstained.” For questions that required specific medical expertise, the pattern of answers from specialists in those fields was evaluated. Voting details for each answer was the source to define the level of concordance as follows: answer options with ≥75% agreement were considered “concordance,” and answer options with ≥90% agreement were considered “strong concordance.”[10]

 » Results Top

[Table 1] provides an overview of the results obtained during the web-based survey and poll. [Table 2] and [Table 3] summarize the areas of agreement ≥90% and ≥75%–89%, respectively, for this Indian survey on PC management. Irrespective of the original sequence (in WBS and CM), the questions in the manuscript are grouped and discussed per their clinical relevance to facilitate understanding as follows: 1) epidemiology and screening, 2) diagnosis and evaluation, 3) management of localized and locally aPC, 4) nonmetastatic castrationresistant PC (nmCRPC), 5) metastatic castration-sensitive PC (mCSPC), and 6) metastatic castrationresistant PC (mCRPC). The agreement (in percentage) reached for each of the questions is specified in parenthesis. The options that were selected by ≤10% of the panelists are not elaborated in the discussion for all the questions, unless the clinical relevance was deemed high.
Table 1: Summary of statements and agreement status during online survey and polling event

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Table 2: Areas of strong concordance (≥90% agreement)

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Table 3: Areas of agreement (≥75%-89% agreement)

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 » Discussion Top

Epidemiology and screening

Cancer registries across different states in India have demonstrated an increasing trend in the incidence rate of PC in the age group of ≥65 years.[16] Also, patients are likely to be diagnosed at advanced stages, leading to a high burden of aPC.

Evidence on the current true incidence rate of PC in India is limited, with very few community-based studies on PC.[7],[9] In a 2006 report, the average annual cancer incidence rate for PC in India ranged from 5.0 to 9.1 per 100,000/year, 85% being detected late (stages III and IV) as compared to the US (15%).[17] However, the growing awareness among the public and screening with serum PSA in India has resulted in a stage and age migration with PC detection at an earlier phase.[18]

Although organized population-based screening has demonstrated reduced mortality, there is a strong association with overdiagnosis and an increased need for resources.[19],[20] The US Preventive Services Task Force (US PSTF) 2018 recommends against PSA-based screening for men aged ≥70 years and encourages periodic PSA-based screening for men aged 55–69 years after individual discussion with regard to benefits and harms.[21] The ESMO and EAU guidelines recommend an individualized risk-adapted strategy for early detection to a well-informed man and a life-expectancy of at least 10–15 years.[12],[13] In a large country like India, with resource limitations and potential harms of false-positive results and treatment complications, opportunistic screening (individual case findings, initiated by physician or patient) seem to be a viable option.

Diagnostics and evaluation

PC being a heterogeneous disease, ranging from indolent low-grade to aggressive tumors, evaluation of local and distant cancer extension remains crucial for estimating prognosis and guiding treatment.

Biochemical evaluation

Elevated PSA (>4 ng/mL), though seen at presentation in 80% of PC, seldom alone identifies PC correctly (only 25%–30% of the time). At least two abnormal PSA levels or palpable nodule on DRE is said to justify biopsy and further investigation.[22] Multiparametric MRI is increasingly being used to identify patients with clinically significant PC, as exclusive PSA-based diagnosis lacks sensitivity and specificity.[23] Biopsy can be better guided by evidence of PSA dynamics, clinical progression on DRE, or radiological progression on mpMRI. Access to mpMRI and cost may be deterrents in India, but the potential to reduce the diagnosis of low-risk PC, cost of unnecessary biopsy procedures and treatments, or their complications may prove cost-effective in the long run.

Traditionally, normal PSA levels are defined as ≤4 ng/mL.[24] The panelists highlighted that the mean and age-specific PSA tends to be lower in Indians than in the Western population. A rural community-based study of 1899 Indian men reported an age-specific PSA value of 2.1, 3.4, 4.2, and 5.0 for men in fourth, fifth, sixth, and seventh decades of their life, respectively.[25] These values are marginally lower than the western standard values, which are 2.5, 3.5, 4.5, and 6.5 ng/mL for the same age cohorts.[26]

A real-world study suggested that because the age-specific PSA range tends to be lower in Indians, raising the cut-off for biopsy in symptomatic men with negative DRE to 5.4 ng/mL can help avoid subjecting 10% of men to unnecessary biopsy.[18] The ESMO guidelines recommend that limited PSA elevation alone should not prompt immediate biopsy; PC risk calculator and/or mpMRI should be used to confirm the indication for biopsy.[13] According to EAU guidelines, the need for prostate biopsy is based not only on PSA level and/or suspicious DRE and/or imaging but also on factors such as age, potential comorbidity, and therapeutic consequences.[12]

Pathological evaluation

TRUS prostate biopsy remains the gold standard to facilitate diagnosis for PC. The EAU guidelines recommend 10–12 core biopsies based on level, and DRE and imaging, especially in the larger prostates, with >12 cores not contributing to a conclusive diagnosis.[12] The NCCN guidelines mention TRUS-guided biopsies for a definitive diagnosis but do not specify the number of cores.[11] Results from PROMIS, a multicenter, paired-cohort study to test the diagnostic accuracy of mpMRI and TRUS-biopsy, determined that using mpMRI to triage men might avoid a primary biopsy in 27% of patients and diagnose 5% fewer clinically insignificant cancers.[27] An Asian study reported that mpMRI has a promising specificity for negative PC on systematic biopsy and MRI-negative patients. The combination of 12-core systematic and mpMRI/TRUS fusion-guided biopsies allowed a significantly higher cancer detection rate compared with a systematic biopsy (33.3% vs. 17.6%; P = 0.01).[28] These results led to a strong recommendation from the EAU guidelines to consider an mpMRI before a TRUS prostate biopsy.[12] Our survey revealed that the combination of systematic and MRI-targeted biopsies is preferred to systematic biopsies alone in the repeat biopsy setting, especially when available and affordable. The NICE guidelines also suggest MRI-guided prostate biopsy to be more cost-effective than systematic prostate biopsy as it is more efficient in identifying clinically significant cancer and takes less time. A study reported that TRUS-guided prostate biopsy in the elderly with high PSA (mean: 81.3 ng/mL) can reduce the number of required cores per biopsy and recommended a sextant biopsy even in the elderly to reduce the risk of detection loss.[29] Another study, which used a nomogram, based on age and prostate volume revealed that cancer detection rate allocating 6–12 core biopsies in daily practice has similar efficacy as compared with more biopsy cores and that number of cores can be reduced in older patients.[30]

Similar to our survey, the College of American Pathologists (CAP) Reporting Guidelines for RP mention histologic type, histologic grade (such as Gleason primary pattern and Grade group), tumor quantitation (such as the number of positive cores and the total number of cores), EPE, seminal vesicle/urinary bladder neck invasion, and margins as essential data elements, while lymphovascular and perineural invasion were listed as additional elements.[31] The EAU guidelines[12] suggest the following mandatory elements in an RP specimen report: histopathological type, grading according to International Society of Urological Pathology (ISUP), presence of intraductal carcinoma, tumor (sub) staging, and surgical margin status: EPE, bladder neck or seminal vesicle invasion, location and extent of positive surgical margins, and additional information may be provided on multifocality and diameter/volume and zonal location of the dominant tumor.

Importance of neuroendocrine differentiation on pathology

This result is aligned with the NCCN recommendation to consider small cell/NED in patients who are positive for metastases, no longer respond to androgen deprivation therapy (ADT), and have the initial Grade Group 5 pattern. Association of NED with low PSA levels despite large metastatic burden and visceral spread is also well recognized. A prospective study in 202 patients with mCRPC who underwent metastatic biopsies reported NED histology in 17%.[32]

Need for risk stratification: Further evaluation, counseling for therapy, and prognosis

To facilitate treatment decisions, patients diagnosed with localized PC are stratified into distinct risk groups (low-risk, intermediate-risk, or high-risk) such as the D'Amico risk stratification, based on the clinicopathological features.

Imaging to stratify burden of PC

Multiparametric MRI is the current gold standard for local staging and detection of PC; however, it has been shown to inadvertently miss pivotal tumor lesions and underestimate their volume.[33] A diagnostic meta-analysis reported high specificity but poor and heterogeneous sensitivity with MRI for local PC staging; however, correct tumor stage prediction improved when MRI findings were combined with D'Amico risk categories.[34],[35] PSMA-PET-CT is emerging as a promising technique with high sensitivity and specificity for tumor and LN detection, staging, focal therapy guidance, and noninvasive PC characterization.[27],[36] A recent retrospective analysis demonstrated that PSMA PET-CT was able to identify advanced disease in more than one-third of patients with high-risk disease.[37] The PSMA-PET sensitivity for identifying ISUP grade 2 and 3 PC was 100% with overall superior diagnostic accuracy in ISUP grade ≥2 compared with mpMRI.[38]

The panelists discussed the high sensitivity and specificity of PSMA-PET-CT for nodal disease and bony metastasis in omPC and that the NCCN guidelines have excluded PSMA-PET, pending Food and Drug Administration approval (therefore unavailable in the US). However, in India, PSMA-PET is considered a one-stop imaging modality, with facilities being readily available at an economical cost of 200–300 USD (more economical than mpMRI + bone scan). The panelists concluded that mpMRI alone may be adequate in a low-risk patient, but a PSMA-PET scan should be considered in a high-risk patient. A small retrospective cohort (n = 20) recently reported an important role for PSMA-PET-CT in identifying men with true omPC who could benefit the most from metastases-targeted radiotherapy (RT).[39]

Despite growing research in the area, the definitions for omPC are amorphous. Although PSMA is sensitive and specific in quantifying metastases, there was a concordance in defining omPC at <3 sites with no visceral involvement. The American Society of Clinical Oncology defines omPC by the presence of ≤5 metastatic sites on imaging.[40] In the APCCC 2019,[10] 46% of panelists voted for a limited number of synchronous or metachronous metastases in the bone or LN, but not in visceral organs, while 48%, 41%, and 11% of panelists voted for a cut-off of ≤3 metastases, ≤5 metastases, and any number of metastases that can be treated safely with ablative intent, respectively, to define omPC. The considerable variation in practice reflected the choice and availability of imaging techniques to define oligometastatic disease. The Asia Pacific (APAC) APCCC 2017[41] identified factors influencing the approach to management of omPC: 1) limited availability of imaging technologies, such as PSMA-PET in many APAC countries; (2) challenge of recommending metastasis-directed treatments (such as surgery or stereotactic body RT) that carry additional cost in the absence of evidence for a survival benefit; and (3) whether treatment is being undertaken with long-term control/curative intent. The EORTC imaging group recommend PSMA for imaging omPC (whole-body MRI and choline PET-CT may be used depending on clinical circumstance).[42] Although PSMA-PET-CT is more sensitive and specific than CT or bone scintigraphy, it remains unclear whether changes in management, when identifying omPC, translate to better patient outcomes. Presently, reduction of false-positive results due to greater specificity and reporter agreement with PSMA-PET-CT has resulted in its widespread adoption where it is available and affordable. Overall, panelists agreed that PSMA-PET-CT is a good tool for this subset in India because of high precision, easy accessibility, and affordability.

Importance of Multidisciplinary Team (MDT)

An evolving therapeutic landscape with increasingly complex combinations of systemic and local therapies, advances in imaging, and germline and somatic genetic testing demands an interdisciplinary and holistic approach for managing PC. Shared decision-making with an uro-oncology MDT panel can optimize individual patient therapy based on evidence-based scientific and clinical data deliberations by specialists in the field of urology, oncology, radiation-oncology, pathology, radiology, and nuclear medicine.[43] The panelists deliberated that the high proportion affirming access to MDT may not be representative of the real-world Indian practice scenario and may reflect an informal MDT that involves radiologists and oncologists for complicated cases. One retrospective audit reported poor MDT referral (28%) for PC in clinical practice as compared to upper gastrointestinal or lung cancer (90%–100%).[44] Conversely, one recent survey in India revealed that only 19% of respondents did not have MDT meetings in their institution, while 37% discussed most of their patients with MDT; however, the survey indicated a scope to enhance MDT collaboration to better patient outcomes in PC.[45] The APAC APCCC 2017[41] consensus highlighted the “real-world” considerations and critical importance of an MDT-based approach to optimize patient care while encouraging virtual MDT to address geographical challenges and poor access to specialist cancer centers in some APAC countries.


Localized and locally advanced PC

The primary options for management of this group of PC include active surveillance (AS), RP, and radical RT.


The panel discussed the different facets of watchful waiting and concluded that it is crucial to consider the age, comorbidity, and life expectancy of patients. Several studies have evaluated the advantages of AS in low-risk PC patients.[46],[47] The ProtecT trial compared AS, RP, and RT for clinically localized PC and revealed that after a median follow-up of 10 years, there was no significant difference between the three treatment arms and the PC-specific mortality (PCSM) was extremely low at 0.7–3.0 (1.5 per 1000 patient-years). Radical prostatectomy and RT were associated with lower rates of disease progression than AS; however, 44% of the patients assigned to AS avoided side effects (did not receive radical treatment).[48] The NCCN guidelines[11] recommend AS for all men with very-low-risk PC and life expectancy <20 years, while the EAU guidelines[12] recommend watchful waiting for asymptomatic patients with a life expectancy of <10 years and AS to patients with a life expectancy of >10 years and low-risk disease. Although no standard protocol exists for active monitoring across international guidelines, regular PSA testing, biopsies, and patient counselling about the potential need for treatment in the future are imperative.

Treatment modalities

Our survey is concordant with the EAU guidelines,[12] which recommend that individual preferences should be a primary consideration in shared decision-making for optimizing treatment decisions. A systematic review reported that shared decision-making for men receiving PC therapy has a positive but short-term effect on the patient-perceived quality of life (QoL).[49] The NICE guidelines[15] recommend counseling by a healthcare professional (e.g., a consultant/specialist nurse), supported by written and visual media. NICE guidelines suggest discussing all relevant management options, their risks, and benefits in an objective, unbiased manner, specifying limited evidence for some treatment options.

An analysis in Indian patients on outcomes following robot-assisted RP reported continence rates of >90% in high-risk PC, with adjuvant treatment not necessitated in two-thirds of the patients.[50] Results from the United in Fight against prOstate cancer (UFO) multicenter, prospective registry revealed that while robot-assisted RP prevailed in Malaysia and Singapore, laparoscopic procedures dominated in China and India (compared to robot-assisted or open procedures).[51] The robotic approach surely looks popular in India, but clinicians would counsel eligible patients about the pros and cons to help them make an informed decision.

Several nomograms and algorithms have been developed to predict the risk of LN invasion and determine which patients may benefit from pelvic LN dissection (PLND). Considering the benefit-risk balance, PLND at the time of RP is not recommended in men with low-risk PC. A meta-analysis evaluated the effectiveness of standard versus extended PLND (ePLND) in the survival of PC among men >40 years of age diagnosed with localized PC and showed a biochemical relapse-free survival (BRFS) favoring ePLND.[52] According to EAU guidelines,[12] RP should be accompanied by ePLND in patients with intermediate-risk PC (D'Amico classification) and >5% nomogram (Briganti) predicted risk of positive LN and in all high-risk PC cases. Extended PLND prolongs time to PC-specific survival (PCSS) in intermediate- and high-risk PC patients. The panelists discussed that while variations may exist depending on the nature of practice of a urologist, most patients are of intermediate- and high-risk groups and therefore merit an LND.

Radiation therapy

The role of elective whole-pelvis radiotherapy (WPRT) remains contentious. While the GETUG-01 trial did not find any significant difference in 10-year survival outcomes with WPRT as compared with prostate-only RT, RTOG 9413 showed a significantly better 10-year progression-free survival (PFS) with WPRT over prostate-only RT when combined with neoadjuvant androgen suppression.[53],[54] NICE guidelines currently recommend considering WPRT for patients with high-risk PC with >15% risk of pelvic LN involvement, who are treated with neoadjuvant hormonal therapy and radical RT.[15] Recently, a randomized trial from India (POP-RT) reported the outcomes with WPRT versus prostate-only RT in highrisk and very high-risk, nodenegative PC. Significant improvement was observed with WPRT in the primary endpoint of biochemical failure-free survival as well as diseasefree survival, though not on overall survival (OS). The considerably improved clinical outcomes were achieved with a modest increase in grade 2+ late bladder toxicity with WPRT, with no impact on acute or late bowel toxicities or patient-reported QoL, as the patients were universally treated with bowel-sparing intensity modulated RT (IMRT).[55]

This survey is in congruence with the Phoenix criteria, where biochemical recurrence of PC after curative RT is defined as a PSA rise of ≥2 ng/mL above the nadir.[56] However, with the advent of PSMA-PET, the ability to localize PC recurrences has increased markedly, creating possibilities for the detection of PC recurrence in RT patients with a PSA rise (from the nadir) below the Phoenix PSA threshold of 2.0 ng/mL.[57]

Adjuvant therapy

Results of the GETUG-AFU 16[58] and RTOG[59] trials showed the efficacy of androgen suppression plus RT as salvage treatment in patients with increasing PSA concentration after RP for PC. Salvage RT combined with short-term androgen suppression significantly reduced the risk of biochemical or clinical progression and death compared with sRT alone; 120-month PFS was 64% (95% CI: 58–69) for patients treated with RT plus goserelin and 49% for patients treated with RT alone (hazard ratio (HR): 0·54, 0.43–0.68; P < 0·0001) in the GETUG-AFU 16 trial. Similar to our results, in the APCCC 2019[10] consensus, for asymptomatic pN0 patients with PSA persistence after RP and no evidence of macroscopic disease, 66% of panelists voted for sRT plus systemic hormonal treatment, while 28% voted for PSA surveillance without immediate active treatment.

In the post-RP setting, the prognosis is determined by the presence of various adverse features. A meta-analysis based on older trials evaluating aRT versus observation after RP reported no benefit in OS but improved biochemical and local PFS with aRT. However, it reported a likelihood of overtreatment, with 35%–60% of patients being biochemical recurrence-free with observation alone, along with an increase in adverse effects with aRT.[60] The recently reported RADICALS-RT and RAVES trials compared aRT and sRT in post-RP patients with at least one high-risk factor for biochemical progression, with sRT being triggered at PSA levels of 0.1–0.2 ng/mL. Both of them reported similar 5-year biochemical relapse-free survival rates for aRT and sRT, but higher genitourinary toxicity with aRT.[61],[62] GETUG-AFU17 trial also reported a similar increase in late grade 2+ genitourinary and erectile dysfunction with aRT versus sRT, with no difference in 5-year event-free survival in patients post-RP with positive margins.[63] The ARTISTIC meta-analysis of these trials concluded that post-RP aRT does not improve event-free survival over sRT in patients with localized PC and additional therapy was avoidable in about half of post-RP patients with adverse pathology who did not develop recurrent disease in their lifetime.[64] However, patients with multiple adverse prognostic features were grossly under-represented in this meta-analysis, with a 5-year event rate of only 20% in this subgroup, which is much lower than predicted by the Cancer of the Prostate Risk Assessment-post surgical score (CAPRA-S) nomogram. Currently, aRT is a recommended option in highly selected patients with combined high-risk features such as pT3/R1/GS 8-10. The pattern of voting in this question relates to the discretion of clinicians using their judgment to choose the few who could be taken up for immediate aRT versus early sRT.

Our survey reflects that the addition of ADT to RT in the postRP setting is well established, but the type of ADT, timing, and duration remain to be systematically examined.[9] Results from the RADICALS-HD arm of RADICALS trial, where 24% (154/649) of the patients in the aRT group received neoadjuvant or adjuvant hormone therapy and were randomized to receive 6 months (n = 90) versus 24 months (n = 45) of hormone therapy versus no hormone therapy are awaited and may answer some of these questions.[62]

Although literature evidence favors a PSA threshold of 0.05–0.1 for early sRT (per RAVES study), 69% of the panelists voted for the 0.2 threshold. In the EORTC trial, immediate postoperative RT after RP (compared with the wait-and-see group) demonstrated improved biochemical PFS.[65] A retrospective analysis of node-negative patients with detectable post-RP PSA levels determined that early sRT initiated at PSA levels of ≤0.2 was associated with reduced rates of both PC-specific mortality (PCSM) and all-cause mortality (ACM) compared with sRT at higher PSA; the 10-year PCSM rate was 5% for patients with a pre-sRT PSA of ≤0.20 ng/mL; 6% for patients with a PSA of 0.21–0.5 ng/mL; 8% for those with a PSA of 0.51–1.0 ng/mL; 18% for patients with a PSA of 1.01–2.0 ng/mL; and 22% for those with a PSA of >2.0 ng/mL.[66] Our survey findings are supported by the NCCN[11] guidelines, which recommend that post-RP sRT is more effective when pretreatment PSA is low.

In men who were LN positive (LN+) after RP, ADT + RT improved survival over either observation or adjuvant ADT alone; however, the duration of ADT was highly variable.[67] A retrospective study including data from the National Cancer Data Base, a hospital-based cancer registry in the US, for patients with LN+ following RP demonstrated improved OS in the majority of patients on aRT + ADT, especially those with adverse pathologic features.[68] A recent meta-analysis revealed a significant impact on OS and PCSS with the concomitant administration of aRT and ADT in patients with LN + PC.[69] The NCCN guidelines recommend at least 2–3 years of long-term ADT when combined with pelvic radiation.

Nonmetastatic Castration-resistant PC

Nonmetastatic CRPC is considered a heterogeneous stage with a variable potential for progressing to the mCRPC stage.[70] Because the sensitivity for detection of metastases with current standard imaging techniques seems to be limited (42%; 95% CI: 0.26–0.56),[71] the emergence of PSMA-PET-CT and whole-body MRI may define the true extent of the nmCRPC population.

The RADAR-1 group consensus suggests bone scan and CT scan when PSA reaches 2 ng/mL and if negative repeat again when PSA reaches 5 ng/mL and then after every doubling of PSA, where PSA testing is done every 3 months for asymptomatic men.[72] The RADAR-III group recommends next-generation imaging such as PSMA-PET-CT only if PSADT is <6 months and when therapies for the M1 stage would be appropriate.[73] PSMA-PET-CT has demonstrated higher sensitivity and specificity for staging prior to RT, especially in patients with biochemical recurrence after surgery.[74] A retrospective study evaluating definitive RT in nmCRPC after median hormonal therapy for 18 months demonstrated long-term (8 years) disease-free and clinical failure-free status in about 25% and 50% of patients, respectively, alongside favorable local relapse-free (91%) and OS (49.8%) rates.[75]

The approval of enzalutamide, apalutamide, and darolutamide for delaying metastases in nmCRPC (NCCN: category 1 recommendation) with a PSA-doubling time of ≤10 months is further changing the treatment landscape.[11] Following a phase II trial with 87.8% of nmCRPC patients free of radiological progression after 2 years of enzalutamide therapy, the phase III PROSPER study reported superior MFS (36.6 months (enzalutamide) vs. 14.7 months (placebo), HR = 0.29, P < 0.0001) and OS (67 months (enzalutamide) vs. 56.3 months (placebo), HR = 0.73, P < 0.001).[76],[77] With apalutamide and darolutamide not being available in India, enzalutamide would remain the mainstay of treatment for nmCRPC.

Metastatic PC

The treatment scenario for mCSPC has rapidly evolved over the last decade. ADT monotherapy is no longer considered the standard therapy in mPC and is giving way to combination with docetaxel, abiraterone, enzalutamide, or RT to the primary tumor. However, the lack of a direct comparison between the treatment modalities makes clinical decision-making in this patient group still challenging.

Role of ADT

The agreement was divided for determining the T level synonymous with castration for patients on ADT. Historically, a castrate threshold of <50 ng/dL has been considered to be associated with improved clinical outcomes. However, recent studies report better clinical outcomes at a lower threshold of <20 ng/dL. One such study reported higher 10-year biochemical recurrence rates (28.1% vs. 18.3%) and metastasis rates (12.9% vs. 7.8%) persisting on multivariable analyses in the 20–49-ng/dL group compared with the <20-ng/dL group.[78] Similarly, over a median follow-up of 125 months, patients with a T of <20 ng/dL had better BRFS in addition to better prediction of BRFS and a real-world retrospective review in patients who initiated continuous ADT (2006–2017) reported had a significantly increased time to CRPC and longer PFS in the <20-ng/dL group.[79],[80] The panelists concluded that although most studies and registered trials accept a castrate level of T <50 ng/dL, castrate levels of ≤20 ng/dL have a seemingly better outcome.

The majority of the panelists (98%) opted for some option of medical castration, particularly for a limited duration need, of which leuprolide was a choice among 45%. Although this agreement of medical castration was favorable, the panelists opined that results might reflect the belief of leuprolide being cost-friendly or being widely used. The UFO registry, a multicenter, cohort study of aPC in Asia, showed a high proportion of M1 patients with de novo metastases (94.1%) in India, with ADT (either BO or LHRH analogs) being the most common treatment for M0 and mCSPC. Among patients with M1 PC, orchiectomy was performed more frequently in India (56%) and Thailand (58%) than in other studied countries.[51] The panelists discussed that in the current era, BO is a one-time cost-saving solution, with no compliance and fewer metabolic issues, taking into consideration patient willingness for surgery. Recent studies reported that BO was not associated with differences in survival compared with medical castration and had significantly lower risks of adverse events such as fractures, peripheral arterial disease, and cardiac-related complications compared with those treated with LHRH-A.[81],[82] Thus, in some patients who need permanent androgen suppression, surgical castration may represent a suitable alternative to medical castration. The APAC APCCC 2017[41] reported a consensus for use of BO as ADT in metastatic disease (90%), in the setting of limited healthcare resources. However, the choice of BO over a LHRH-A or antagonist requires consideration of patient preference (sociocultural and psychological barriers), FU requirements, and cost. Many panelists in APCCC indicated that patients in the APAC region would be more likely to choose medical ADT over surgery and emphasized the need to provide men with clear information about options that includes potential benefits, side-effects, and cost. According to the EAU guidelines,[12] primary ADT has been the standard of care for over 50 years; however, there is no high-level evidence in favor of a specific type of ADT, neither for BO or for LHRH-A or antagonist, with the exception of patients with impending spinal cord compression, for whom either a BO or LHRH antagonists are the preferred options. Our results reflect a practice pattern where the slow effects by LHRH-A were consciously avoided in such emergent situations. With respect to LHRH antagonists, NICE guidelines elucidate that there is considerable uncertainty and lack of robust evidence confirming the long-term effect of degarelix on reducing the risk of cardiovascular (CV) events compared with LHRH-A.[83] Recently, promising results were shown by relugolix, an oral LHRH antagonist that achieved rapid, sustained suppression of T levels superior to leuprolide, with a 54% lower risk of major adverse CV events in a phase III trial of aPC[84]; however, its effectiveness in the real world needs to be proven.

Initiation of LHRH-A may be associated with an initial worsening of the bone metastasis symptoms by way of the initial LH and T surge. Guidelines recommend a first-generation antiandrogen (NCCN: ≥7 days, EAU-ESTRO-SIOG: short-term) to precede/coadminister with LHRH-A to prevent T flare in patients with overt metastasis in weightbearing bone and at risk of developing symptoms.[11],[12] Our results were similar to the APCCC 2019[10] where 68% of the panelists voted for a short course of a first-generation NSAA, 30% only if at risk of harm from flare, and 2% voted against flare protection. The panelists concluded that prevention of flare may be the only remaining role for NSAA in practice today.

There was a strong agreement in the WBS for alteration in management strategy when there is T escape on LHRH-A. Patients on medical castration should have regular T testing to ensure castration as studies report an overall T escape of 2%–13%, with up to 17% of patients failing to achieve T <50 ng/dL and up to 38% failing to achieve T <20 ng/dL.[85]

Metastatic castration-sensitive PC

Role of docetaxel in mCSPC

Since 2015, the standard of care for mCSPC has changed from ADT to combination therapy. The CHAARTED[86] and STAMPEDE (arm C)[87] trials were the first to demonstrate upfront docetaxel added to ADT improves OS in patients with mCSPC. LATITUDE[88] and STAMPEDE (arm G)[89] trials reported a higher OS improvement with upfront abiraterone plus prednisone when combined with ADT. Improvement in prognosis in mCSPC presented clinicians with more evidence-based options but also presented a challenge for individual treatment optimization as no further direct comparisons between docetaxel and abiraterone explored superiority. A network meta-analysis (LATITUDE, CHAARTED, and GETUG-AFU 15) reported similar OS with abiraterone versus docetaxel; however, abiraterone was superior in preventing disease progression and enhancing QoL.[90] However, the efficacy of docetaxel is reported to be lower if used after abiraterone or enzalutamide,[91] creating a rationale for initial docetaxel use. Docetaxel therapy at 6–9 cycles may be cost-effective compared with the life-long use of abiraterone.[90] A cost-effective analysis in Hong Kong reported docetaxel to be a more cost-effective strategy in developed economies.[92]

The panelists deliberated that probably at 4–6 weeks post-ADT, patients are more fit to receive docetaxel CT, leading to an increase in vote during the CM for this dosing interval. Concurrent ADT without achieving castrate levels can affect the pharmacokinetics by increased uptake of docetaxel in the liver with an increase in odds of febrile neutropenia.[93] However, a retrospective analysis reported no association between docetaxel initiation time in relation to ADT and docetaxel-related toxicity.[94] A recent expert panel recommendation advises the use of docetaxel 6–16 weeks after ADT to avoid toxicities.[95]

The standard dose of docetaxel is 75 mg/m2 every 3 weeks for 6 cycles (NCCN recommendation based on CHAARTED trial).[11] The high agreement reached for 3-weekly docetaxel by our panelists aligns with the recommended dose schedule. Because reduced docetaxel relative dose intensity has been associated with worse OS, careful patient selection and upfront use of growth factors are recommended to ensure standard dose and schedules.

Role of combination therapy in low-volume and high-volume mCSPC

The definition of low-volume (LV) versus high-volume (HV) mCSPC has been contentious. However, in recent times, the CHAARTED[86] study definition for HV mCSPC as patients who have visceral metastases or have ≥4 bone metastases with lesions beyond pelvis/vertebral bodies is now widely accepted. Recent trials with docetaxel and abiraterone demonstrate that treatment selection may be optimized to some extent based on disease volume.

Our survey panel equally favored abiraterone + prednisolone or local treatment in combination with either docetaxel or abiraterone or enzalutamide (41.5% each) in LV mCSPC. Although the CHAARTED trial[86] demonstrated a significant 13.6 months' improvement in OS, making docetaxel addition to ADT as the standard of care in mCSPC, an updated analysis in 2018 confirmed a 16.8 months' OS improvement only in HV disease, with no benefit in LV disease (HR: 1.04, 95% CI: 0.70–1.55, P = 0.86).[96] Similarly, a meta-analysis of the CHAARTED and GETUG-AFU 15 trials with docetaxel did not report benefits for men with LV mCSPC.[97] However, a retrospective analysis of STAMPEDE, which stratified the metastatic burden found no heterogeneity (interaction P = 0.827) in docetaxel survival benefit, with risk reduction being consistent in low (HR: 0.76, 95% CI: 0.54–1.07, P = 0.107) and high-burden (HR: 0.81, 95% CI: 0.64–1.02, P = 0.064) subgroups.[98] As the abiraterone trials (LATITUDE[88] and STAMPEDE arm G[89]) did not analyze benefits based on disease volume and have not shown a lack of benefit in either the LV or HV subset, their present recommendation in mCSPC is irrespective of volume status. There are no comparative trials studying the efficacy of docetaxel versus abiraterone in LV mCSPC.

Our survey echoes the APCCC 2019[10] consensus for HV mCSPC, where additional treatment in combination with ADT is preferred as opposed to ADT alone. With strong survival benefits proven in the HV subgroup in the GETUG-15, CHAARTED, and STAMPEDE arm C trials, there is a strong case for docetaxel as the standard of care in this patient group before other therapies. However, abiraterone benefits in LATITUDE and STAMPEDE arm G (no volume-based results available) make it an alternate standard of care option in this patient group. In the APCCC 2019[10] consensus, 56% voted for the addition of either docetaxel or one of the androgen receptor-targeted agents (ARTAs) to ADT in de novo HV mCSPC, with a similar consensus for HV mCSPC relapsing after local treatment of primary tumor. Docetaxel may be considered for those who desire shorter treatment duration or economical options and have good PS, while abiraterone can be an option for those who desire to reduce hospital visits for CT infusions.[99] The ENZAMET trial with enzalutamide reported longer PSA-PFS (HR: 0.39; P < 0.001) and OS (HR: 0.67; 95% CI: 0.52–0.86; P = 0.002) in mCSPC. However, in those who received prior docetaxel, there was longer PFS but no OS benefit and higher episodes of seizures and other toxic effects.[100] The ARCHES trial with enzalutamide reported a reduced risk of metastatic progression or death (HR: 0.39; 95% CI: 0.30–0.50; P < 0.001) with similar significant improvements irrespective of disease volume or prior docetaxel therapy.[101] A recent review concludes that the correct sequence of AR-targeted therapies remains to be defined with insufficient evidence to support switching between these therapies once patients progress.[102]

Role of local treatment in low-volume and high-volume mCSPC

Our survey aligns with evidence and guideline recommendations as the NCCN[11] based on STAMPEDE results recommend RT only in LV mCSPC. The STAMPEDE study demonstrated a significant 3.7 months' improvement in OS (HR: 0.68, 95% CI: 0.52–0.90, P = 0.007) and failure-free survival (HR: 0.59, 95% CI: 0.49–0.72, P < 0.0001) with RT only in the LV subgroup.[103] The benefits of RT in LV mCSPC reported in STAMPEDE confirmed the HORRAD trial results (trend toward OS benefit; HR: 0.68, 95% CI: 0.42–1.10), a similar design but smaller (n = 432) trial.[104] A meta-analysis (STOPCAP) of aggregate STAMPEDE and HORRAD data identified a 7% improvement in the 3-year OS rate among men who had up to four bone metastases.[105] Results of two ongoing studies, g-RAMPP (NCT02454543) and TROMBONE (ISRCTN15704862), may offer insights into the role of surgery in this patient group.

Although no agreement was reached, a high proportion of panelists voted for the wait-and-watch approach with repeat PSA after 3 months rather than continuing with additional docetaxel cycles (>6) or the addition of second-line therapies. This is consistent with evidence that indicates that an increase in PSA levels alone is not sufficient to prove disease progression[106] as significant increases are reported in 14% of patients during the initial docetaxel cycles.[107]

Metastatic castration-resistant PC

Options for managing patients with mCRPC in India are two CT agents (docetaxel and cabazitaxel), two ARTAs (abiraterone and enzalutamide), targeted therapy (olaparib), and theranostics. Genomic biomarker evaluation is making individualizedtargeted treatments possible, with olaparib being the first poly (ADP-ribose) polymerase inhibitor to prove longer OS in patients with mCRPC and DNA-damage response gene alterations. Optimal mCRPC management is highly dependent on selecting patients who will derive maximum benefit from a particular agent and determining when best to change treatment.

Our results are consistent with the APCCC 2019 consensus where 87% of the panelists voted for the term CRPC to signify patients who progress despite T levels being suppressed to castrate (<50 ng/mL). Both the NCCN[11] and EAU[12] guidelines mandate T evaluation in the situation of rising PSA/clinical progression during ADT. The EAU-ESTRO-SIOG[12] guidelines define CRPC as castrate T levels, accompanied by either biochemical (3 consecutive PSA rise 1 week apart) or radiologic progression (≥2 new bone lesions on bone scan or a soft tissue lesion).

Q49 and Q 55 results point to the need for consideration of multiple factors in a holistic manner before deciding the optimal management protocol in mCRPC. The NCCN confirms the need to incorporate clinical and radiographic criteria while assessing progression and not rely only on biochemical (rising PSA) parameters.[11] The PCWG3 concept of “no longer clinically benefiting (NLCB)” recommends modifying treatment when the patient no longer clinically benefits rather than wait strictly for progression. The NLCB metric recommends individualizing patient decisions based on primary therapeutic objectives being assessed, including QoL or survival.[106]

Role of docetaxel in mCRPC

Per NCCN,[11] docetaxel is the traditional mainstay of treatment (category 1) for those with symptomatic metastases in mCRPC, with a median survival benefit of 2–3 months. Although treatment with ≥8 cycles of docetaxel has demonstrated improved OS in mCRPC, there is a paucity of prospective trials comparing 6 versus 10 cycles.[108] A small retrospective study (n = 73) in mCRPC reported no significant difference in survival outcomes between the group receiving >10 cycles versus the group that received ≤10 cycles. However, adverse events were more common in the former group; the study concluded that administration of at least four docetaxel cycles is important to confer benefit.[109]

Role of cabazitaxel in mCRPC

Analysis of the medical oncologists' response showed that about 54.5% agree that more than half of the metastatic cohort reach the stage where they require cabazitaxel. Cabazitaxel with concurrent steroid is recommended by NCCN for M1 CRPC systemic therapy in patients intolerant or not suitable for receiving docetaxel CT.[11] The pivotal TROPIC study demonstrated improved OS, PFS, PSA, and radiologic responses at 25 mg/m2 administered for six cycles but also showed significant toxicity in men with mCRPC who progressed on docetaxel.[110] A more recent study (PROSELICA) reported lower toxicity at a lower dose (20 mg/m2), albeit with a lower radiological response, OS and PFS (nonsignificant), and lower PSA response (significant).[111] A small Indian study reported that in select patients, cabazitaxel can be continued beyond 10 cycles as PSA continued to decrease and subjective improvement continued with increasing cycles. However, the study cautioned to carefully monitor for peripheral neuropathy.[112] The CARD trial compared cabazitaxel or alternative AR-targeted therapy (abiraterone/enzalutamide) as third-line treatment in patients with mCRPC who progressed rapidly after prior docetaxel and an alternate AR-targeted therapy. Results demonstrated improved OS, PFS, and PSA response, suggesting cabazitaxel efficacy in patients who progress on docetaxel/ARTAs and resulted in a recommendation for sequencing cabazitaxel after docetaxel in preference to alternate ARTAs.[113] Furthermore, the APCCC 2019 reached a 75% consensus for use of cabazitaxel sometime during the course of mCRPC.[10]

The current survey captures the history of treating CRPC in India and reflects the varied practices across our country. The high concordance for fosfestrol, a low-cost estrogen analog that alters 5-alpha reductase activity, shows the importance of an economic option in resource-scarce settings. A retrospective study in Chennai reported median OS and PFS of 14.7 and 6.8 months, respectively, with a response of PSA >50% in 55% of patients and concluded that fosfestrol is an effective, safe, and economical option in mCRPC progressing after first-line complete androgen blockade.[114] The panel discussed that although theoretically radionuclides are currently not widely used in common practice, the voting pattern indicates a greater role for this in the near future.[115] Theranostics is an emerging therapeutic option with the potential to detect PC with higher sensitivity and precise extirpation ability and is offered in a few centers in India using Lutetium (Lu-177) and Actinium (Ac-225) radionuclides.[116] This advanced system allows the delivery of diagnostic and cytotoxic agents precisely to cancer cells. However, prospective clinical trials with theranostics are still underway and their ability to improve QoL and OS remains to be demonstrated.

Sequencing in mCRPC

Abiraterone, docetaxel, cabazitaxel, and enzalutamide have a category 1 recommendation per the NCCN guidelines in M1 CRPC. However, the ideal sequencing has not been established, with a recent crossover study reporting a longer time to PSA progression when abiraterone was used prior to enzalutamide rather than vice-versa, while a retrospective study confirmed that docetaxel should be considered before second-generation ADT.[117],[118] The optimal sequential use of these therapeutic options holds potential to prolong patient survival in comparison to historical and current therapies but remains to be defined.


There are no clear guideline recommendations for monitoring asymptomatic patients with mPC. The PCWG3 increased the suggested frequency of assessment for bone scans, CT/MRI from every 12 weeks (PCWG2) to every 8–9 weeks for the first 24 weeks, followed by every 12 weeks. However, in long-term responders (>2–3 years of clinical benefit, no signs of clinical/biomarker progression), this frequency was suggested to be reduced to every 16–24 weeks.[106] The asymptomatic patients with stable PSA do not require regular imaging per EAU-ESTRO-SIOG guidelines.[119] Furthermore, routine bone scan/PSMA-PET-CT for monitoring asymptomatic mPC may not be realistic in the Indian scenario despite the reduced cost (compared with western countries) and increased access as the early diagnosis does not necessarily lead to treatment modality changes.

Bone health

A high (90%) prevalence of bone metastases is reported in men who die from PC.[120] Bone metastases result in lower QoL, being associated with pain, pathological fractures, and cord compression. ADT also contributes to skeletal-related events (SRE) by lowering the bone mineral density. Thus, palliative treatments such as bisphosphonates and receptor activator of nuclear factor-kappa B ligand (RANKL)-inhibitors (RANKLi) that reduce or prevent the occurrence of SRE are recommended as supplementary therapies.[121]

Our survey result is aligned with guidelines and studies, which recommend bone-protective agents mainly in mCRPC with skeletal metastases and to prevent osteoporosis in mCSPC. The NCCN opposes early use of zoledronic acid in mCSPC.[11],[122] The CALGB 90202 and ZAPCA studies in patients with mCSPC and bone metastasis reported no benefit of early treatment with zoledronic acid in terms of time to first SRE and OS.[123],[124]

However, post hoc analyses from pivotal phase III studies demonstrate that combination therapy of bisphosphonates or denosumab plus abiraterone or enzalutamide or radium-223 may increase survival in men with mCRPC and prevent skeletal complications.[125–127] The NCCN recommends denosumab or zoledronic acid every 3–4 weeks in mCRPC but mentions that the optimal duration of these agents is unclear.[11] The ESMO recommends the initiation of bisphosphonates or denosumab in patients with mCRPC with bone metastasis and at risk for clinically significant SRE.[13]

 » Conclusion Top

This is one of the first surveys documenting the clinical practice patterns in the management of PC in India. It attempts to identify issues that are specific to the Indian scenario and correlate screening, diagnosis, and treatment patterns with existing literature and guidelines. The survey aims to provide valuable information to guide the management of PC in the face of evolving complexity and availability of technologically advanced diagnostic and newer treatment modalities. The lack of concordance for some areas indicates the lack of using robust data to support clinical decision-making and in some instances, making the best use of the available resources. Reflections from a panel of national experts from across the nation can help clinicians in India navigate the crucial areas of PC management at the regional level for which high-level evidence is sparse. Additionally, this provided an opportunity to identify and review the best treatment practices conducive to India and South East Asia at large, in sync with evolving clinical practices worldwide.[125],[126],[127]

Author contributions

Ganesh Bakshi, Hemant Tongaonkar, and Sanjai Addla contributed to the conception and design of the study; generation, collection, assembly, analysis, and/or interpretation; data analysis; drafting of the manuscript, and critical revision/approval of the manuscript. Vedang Murthy, Santosh Menon, and Amit Joshi contributed to framing the consensus questionnaire and critical revision/approval of the manuscript.

Aditya Pradhan, Abhay Kumar, Abhijit Bapat, Adwaita Gore, Anand Raja, Anil Bradoo, Anita Ramesh, Anup Kumar, Archi Agrawal, Asawari Ambekar, Ashish Joshi, Ashish Singh, Bhupendra Pal, Singh, Deepak Dabkara, Dhiraj Khadakban, Gagan Gautam, Gagan Prakash, Harvinder Singh Pahwa, Hemant Kumar Goel, Jagdeesh Kulkarni, Jeeban Jyoti Mishra, Kaushal Patel, Mahendra Pal, Percy Jal Chibber, Priya Tiwari, Radheshyam Naik, Raghunath S K, Rahul Krishnatry, Rajendra Shimpi, Rakesh Sharma, Rakesh Taran, Sameer Trivedi, Sanjay Nabar, Sanjoy Surekha, Satish Kumar, Satyakam Krishna Sawaimoon, Shailesh Raina, Srivatsa Narasimha, Suresh Advani, Syed Mohammed Ghouse, Vamshi Krishna Muddu, Vashishth Maniar, and Vivek Venkat contributed to critical revision/approval of the manuscript.


The authors would like to thank AstraZeneca Pharma India Ltd for development of this manuscript in collaboration with Dr. Piyalee Pal, M.P.H, from Covance Scientific Services & Solutions Pvt. Ltd. in accordance with GPP3 guidelines. ( Authors also thank Mr Saurabh Desai for the logistic support in this endeavour.

Financial support and sponsorship

Astrazeneca Pharma India Ltd. (Prime), Astellas Pharma India Pvt. Ltd. (Prime), Sun Pharmaceutical Industries Ltd., Emcure Pharmaceuticals Ltd., Ferring Pharmaceuticals Pvt. Ltd.

Conflicts of interest

There are no conflicts of interest.

 » References Top

The Global Cancer Observatory, Globocan 2020. International Agency for Research on Cancer. Prostate cancer factsheet. Available from: [Last accessed on 2021 Jan 04].  Back to cited text no. 1
Dhillon PK, Mathur P, Nandakumar A, Fitzmaurice C, Kumar GA, Mehrotra R, et al. The burden of cancers and their variations across the states of India: The Global Burden of Disease Study 1990–2016. Lancet Oncol 2018;19:1289–306.  Back to cited text no. 2
Indian Council of Medical Research, Department of Health Research – Ministry of Health & Family Welfare, Government of India. Media report 21 September to 27 September 2019. Available from: [Last accessed on 2021 Jan 05].  Back to cited text no. 3
Hassanipour S, Delam H, Arab-Zozani M, Abdzadeh E, Hosseini SA, Nikbakht H-A, et al. Survival rate of prostate cancer in asian countries: A systematic review and meta-analysis. Ann Glob Health 2020;86:2.  Back to cited text no. 4
Emanuele C, European Commission. Epidemiology of prostate cancer in Europe, 2015. Available from: [Last accessed on 2021Jan 05].  Back to cited text no. 5
American Cancer Society. Survival Rates for Prostate Cancer, 2020. Available from: [Lastaccessed on 2021 Jan 05].  Back to cited text no. 6
Hariharan K, Padmanabha V. Demography and disease characteristics of prostate cancer in India. Indian J Urol 2016;32:103–8.  Back to cited text no. 7
[PUBMED]  [Full text]  
Taitt HE. Global trends and prostate cancer: A review of incidence, detection, and mortality as influenced by race, ethnicity, and geographic location. Am J Mens Health 2018;12:1807–23.  Back to cited text no. 8
Jain S, Saxena S, Kumar A. Epidemiology of prostate cancer in India. Meta Gene 2014;2:596–605.  Back to cited text no. 9
Gillessen S, Attard G, Beer TM, Beltran H, Bjartell A, Bossi A, et al. Management of patients with advanced prostate cancer: Report of the advanced prostate cancer consensus conference 2019. Eur Urol 2020;77:508–47.  Back to cited text no. 10
National Comprehensive Cancer Network. Clinical practice guidelines in oncology, prostate cancer version 2. 2020. Available from: [Last accessed on 2021 Jan 05].  Back to cited text no. 11
European Association of Urology, prostate cancer guidelines, Uroweb, 2020. Available from [Last accessed on 2021 Jan 05].  Back to cited text no. 12
Parker C, Castro E, Fizazi K, Heidenreich A, Ost P, Procopio G, et al. Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2020;31:1119–34.  Back to cited text no. 13
Lowrance WT, Breau RH, Chou R, Chapin BF, Crispino T, Dreicer R, et al. Advanced prostate cancer: AUA/ASTRO/SUO guideline part II. J Urol 2021;205:22–9.  Back to cited text no. 14
National Institute for Health and Care Excellence. Prostate cancer: Diagnosis and management NICE guideline [NG131], 2019. Available from [Last accessed on 2021 Jan 04].  Back to cited text no. 15
Budukh A, Bakshi G, Prakash G. Change in the ranking and increasing trend of the prostate cancer from the population-based cancer registries in India. Indian J Urol 2018;34:235–6.  Back to cited text no. 16
[PUBMED]  [Full text]  
Hebert JR, Ghumare SS, Gupta PC. Stage at diagnosis and relative differences in breast and prostate cancer incidence in India: Comparison with the United States. Asian Pac J Cancer Prev 2006;7:547–55.  Back to cited text no. 17
Agnihotri S, Mittal RD, Kapoor R, Mandhani A. Raising cut-off value of prostate specific antigen (PSA) for biopsy in symptomatic men in India to reduce unnecessary biopsy. Indian J Med Res 2014;139:851–6.  Back to cited text no. 18
[PUBMED]  [Full text]  
Matti B, Zargar-Shoshtari K. Opportunistic prostate cancer screening: A population-based analysis. Urol Oncol 2020;38:393–400.  Back to cited text no. 19
Arnsrud Godtman R, Holmberg E, Lilja H, Stranne J, Hugosson J. Opportunistic testing versus organized prostate-specific antigen screening: Outcome after 18 years in the Göteborg randomized population-based prostate cancer screening trial. Eur Urol 2015;68:354–60.  Back to cited text no. 20
US Preventive Services Task Force, Grossman DC, Curry SJ, Owens DK, Bibbins-Domingo K, Caughey AB, et al. Screening for prostate cancer: US preventive services task force recommendation statement. JAMA 2018;319:1901–13.  Back to cited text no. 21
Leslie SW, Soon-Sutton TL, Sajjad H, Siref LE. Prostate cancer. In: StatPearls. StatPearls Publishing: Treasure Island (FL); 2020. Available from: [Last accessed on 2021 Jan 11].  Back to cited text no. 22
Wallis CJ, Haider MA, Nam RK. Role of mpMRI of the prostate in screening for prostate cancer. Transl Androl Urol 2017;6:464–71.  Back to cited text no. 23
Catalona WJ, Smith DS, Ratliff TL, Dodds KM, Coplen DE, Yuan JJ, et al. Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med 1991;324:1156–61.  Back to cited text no. 24
Ganpule AP, Desai MR, Manohar T, Bapat S. Age-specific prostate specific antigen and prostate specific antigen density values in a community-based Indian population. Indian J Urol 2007;23:122–5.  Back to cited text no. 25
[PUBMED]  [Full text]  
Oesterling JE, Jacobsen SJ, Chute CG, Guess HA, Girman CJ, Panser LA, et al. Serum prostate-specific antigen in a community-based population of healthy men. Establishment of age-specific reference ranges. JAMA 1993;270:860–4.  Back to cited text no. 26
Ahmed HU, El-Shater Bosaily A, Brown LC, Gabe R, Kaplan R, Parmar MK, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): A paired validating confirmatory study. Lancet 2017;389:815–22.  Back to cited text no. 27
Ma WK, Ho BS, Lai AS, Lam KC, Chan YS, Yip LK, et al. Multiparametric magnetic resonance imaging/transrectal ultrasound fusion prostate biopsy with semi-robotic navigation in the Chinese population: Initial results. Asian J Androl 2018;20:93–4.  Back to cited text no. 28
Huh JS, Kim BS, Kim YJ, Kim SD, Park KK. The practicality of targeted prostate biopsy procedures on the dominant side of the tumor determined by magnetic resonance imaging in elderly patients with high serum levels of prostate-specific antigen. World J Mens Health 2015;33:188–93.  Back to cited text no. 29
Tanaka N, Shimada K, Nakagawa Y, Hirao S, Watanabe S, Miyake M, et al. The optimal number of initial prostate biopsy cores in daily practice: A prospective study using the Nara Urological Research and Treatment Group nomogram. BMC Res Notes 2015;8:689.  Back to cited text no. 30
College of American Pathologists (CAP). Protocol for the Examination of Radical Prostatectomy Specimens from Patients with Carcinoma of the Prostate Gland, 2020. Available form: [Last accessed on 2021 Jan 05].  Back to cited text no. 31
Aggarwal R, Huang J, Alumkal JJ, Zhang L, Feng FY, Thomas GV, et al. Clinical and genomic characterization of treatment-emergent small-cell neuroendocrine prostate cancer: A multi-institutional prospective study. J Clin Oncol 2018;36:2492–503.  Back to cited text no. 32
Spohn S, Jaegle C, Fassbender TF, Sprave T, Gkika E, Nicolay NH, et al. Intraindividual comparison between 68Ga-PSMA-PET/CT and mpMRI for intraprostatic tumor delineation in patients with primary prostate cancer: A retrospective analysis in 101 patients. Eur J Nucl Med Mol Imaging 2020;47:2796–803.  Back to cited text no. 33
Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al. EAU guidelines on prostate cancer. Part 1: Screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol 2014;65:124–37.  Back to cited text no. 34
de Rooij M, Hamoen EH, Witjes JA, Barentsz JO, Rovers MM. Accuracy of magnetic resonance imaging for local staging of prostate cancer: A diagnostic meta-analysis. Eur Urol 2016;70:233–45.  Back to cited text no. 35
Bouchelouche K, Choyke PL. Advances in PSMA Positron Emission Tomography (PET) of prostate cancer. Curr Opin Oncol 2018;30:189–96.  Back to cited text no. 36
Monteiro F, Serafim J, Jesus R, Cavalcante P, Gomes G, Hochhegger B, et al. The role of 68Ga-PSMA PET/CT on staging of high-risk localized prostate cancer: For all high-risk patients or would it be better to select them? Prostate Int 2020. doi: 10.1016/j.prnil. 2020.07.007.  Back to cited text no. 37
Scheltema MJ, Chang JI, Stricker PD, van Leeuwen PJ, Nguyen QA, Ho B, et al. Diagnostic accuracy of 68 Ga-prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) and multiparametric (mp) MRI to detect intermediate-grade intra-prostatic prostate cancer using whole-mount pathology: Impact of the addition of 68 Ga-PSMA PET to mpMRI. BJU Int 2019;124(Suppl 1):42–9.  Back to cited text no. 38
Ong WL, Koh TL, Lim Joon D, Chao M, Farrugia B, Lau E, et al. Prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA-PET/CT)-guided stereotactic ablative body radiotherapy for oligometastatic prostate cancer: A single-institution experience and review of the published literature. BJU Int 2019;124(Suppl 1):19–30.  Back to cited text no. 39
Rao A, Vapiwala N, Schaeffer EM, Ryan CJ. Oligometastatic prostate cancer: A shrinking subset or an opportunity for cure? Am Soc Clin Oncol Educ Book 2019;39:309–20.  Back to cited text no. 40
Chiong E, Murphy DG, Akaza H, Buchan NC, Chung BH, Kanesvaran R, et al. Management of patients with advanced prostate cancer in the Asia Pacific region: 'Real-world' consideration of results from the Advanced Prostate Cancer Consensus Conference (APCCC) 2017. BJU Int 2019;123:22–34.  Back to cited text no. 41
deSouza NM, Liu Y, Chiti A, Oprea-Lager D, Gebhart G, Van Beers BE, et al. Strategies and technical challenges for imaging oligometastatic disease: Recommendations from the European Organisation for Research and Treatment of Cancer imaging group. Eur J Cancer 2018;91:153–63.  Back to cited text no. 42
Heidenreich A. Multidisciplinary team meetings for prostate cancer treatment: We can do much better in daily life. Oncol Res Treat 2019;42:363–5.  Back to cited text no. 43
Atwell D, Vignarajah DD, Chan BA, Buddle N, Manders PM, West K, et al. Referral rates to multidisciplinary team meetings: Is there disparity between tumour streams? J Med Imaging Radiat Oncol 2019;63:378–82.  Back to cited text no. 44
Murthy V, Mallick I, Arunsingh M, Gupta P. Prostate radiotherapy in India: Evolution, practice and challenges in the 21st century. Clin Oncol (R Coll Radiol) 2019;31:492–501.  Back to cited text no. 45
Tosoian JJ, Mamawala M, Epstein JI, Landis P, Wolf S, Trock BJ, et al. Intermediate and longer-term outcomes from a prospective active-surveillance program for favorable-risk prostate cancer. J Clin Oncol 2015;33:3379–85.  Back to cited text no. 46
Klotz L, Vesprini D, Sethukavalan P, Jethava V, Zhang L, Jain S, et al. Long-term follow-up of a large active surveillance cohort of patients with prostate cancer. J Clin Oncol 2015;33:272–7.  Back to cited text no. 47
Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, et al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med 2016;375:1415–24.  Back to cited text no. 48
Martínez-González NA, Plate A, Markun S, Senn O, Rosemann T, Neuner-Jehle S. Shared decision making for men facing prostate cancer treatment: A systematic review of randomized controlled trials. Patient Prefer Adherence 2019;13:1153–74.  Back to cited text no. 49
Gupta NP, Murugesan A, Kumar A, Yadav R. Analysis of outcome following robotic assisted radical prostatectomy for patients with high risk prostate cancer as per D'Amico classification. Indian J Urol 2016;32:115–9.  Back to cited text no. 50
Uemura H, Ye D, Kanesvaran R, Chiong E, Lojanapiwat B, Pu Y-S, et al. United in Fight against prOstate cancer (UFO) registry: First results from a large, multi-centre, prospective, longitudinal cohort study of advanced prostate cancer in Asia. BJU Int 2020;125:541–52.  Back to cited text no. 51
García-Perdomo HA, Correa-Ochoa JJ, Contreras-García R, Daneshmand S. Effectiveness of extended pelvic lymphadenectomy in the survival of prostate cancer: A systematic review and meta-analysis. Cent European J Urol 2018;71:262–9.  Back to cited text no. 52
Pommier P, Chabaud S, Lagrange J-L, Richaud P, Le Prise E, Wagner J-P, et al. Is there a role for pelvic irradiation in localized prostate adenocarcinoma? Update of the long-term survival results of the GETUG-01 randomized study. Int J Radiat Oncol Biol Phys 2016;96:759–69.  Back to cited text no. 53
Roach M, Moughan J, Lawton CAF, Dicker AP, Zeitzer KL, Gore EM, et al. Sequence of hormonal therapy and radiotherapy field size in unfavourable, localised prostate cancer (NRG/RTOG 9413): Long-term results of a randomised, phase 3 trial. Lancet Oncol 2018;19:1504–15.  Back to cited text no. 54
Murthy V, Maitre P, Bhatia J, Kannan S, Krishnatry R, Prakash G, et al. Late toxicity and quality of life with prostate only or whole pelvic radiation therapy in high risk prostate cancer (POP-RT): A randomised trial. Radiother Oncol 2020;145:71–80.  Back to cited text no. 55
Roach M, Hanks G, Thames H, Schellhammer P, Shipley WU, Sokol GH, et al. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: Recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys 2006;65:965–74.  Back to cited text no. 56
Jansen BH, van Leeuwen PJ, Wondergem M, van der Sluis TM, Nieuwenhuijzen JA, Knol RJJ, et al. Detection of recurrent prostate cancer using prostate-specific membrane antigen positron emission tomography in patients not meeting the phoenix criteria for biochemical recurrence after curative radiotherapy. Eur Urol Oncol 2021;4:821-5.  Back to cited text no. 57
Carrie C, Magné N, Burban-Provost P, Sargos P, Latorzeff I, Lagrange J-L, et al. Short-term androgen deprivation therapy combined with radiotherapy as salvage treatment after radical prostatectomy for prostate cancer (GETUG-AFU 16): A 112-month follow-up of a phase 3, randomised trial. Lancet Oncol 2019;20:1740–9.  Back to cited text no. 58
Shipley WU, Seiferheld W, Lukka HR, Major PP, Heney NM, Grignon DJ, et al. Radiation with or without antiandrogen therapy in recurrent prostate cancer. N Engl J Med 2017;376:417–28.  Back to cited text no. 59
Bhindi B, Lokeshwar SD, Klaassen Z, Klotz L, Wallis CJ. Systematic review and meta-analysis of trials evaluating the role of adjuvant radiation after radical prostatectomy for prostate cancer: Implications for early salvage. Can Urol Assoc J 2020;14:330–6.  Back to cited text no. 60
Kneebone A, Fraser-Browne C, Duchesne GM, Fisher R, Frydenberg M, Herschtal A, et al. Adjuvant radiotherapy versus early salvage radiotherapy following radical prostatectomy (TROG 08.03/ANZUP RAVES): A randomised, controlled, phase 3, non-inferiority trial. Lancet Oncol 2020;21:1331–40.  Back to cited text no. 61
Parker CC, Clarke NW, Cook AD, Kynaston HG, Petersen PM, Catton C, et al. Timing of radiotherapy after radical prostatectomy (RADICALS-RT): A randomised, controlled phase 3 trial. Lancet 2020;396:1413–21.  Back to cited text no. 62
Sargos P, Chabaud S, Latorzeff I, Magné N, Benyoucef A, Supiot S, et al. Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localised prostate cancer after radical prostatectomy (GETUG-AFU 17): A randomised, phase 3 trial. Lancet Oncol 2020;21:1341–52.  Back to cited text no. 63
Vale CL, Fisher D, Kneebone A, Parker C, Pearse M, Richaud P, et al. Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: A prospectively planned systematic review and meta-analysis of aggregate data. Lancet 2020;396:1422–31.  Back to cited text no. 64
Bolla M, van Poppel H, Collette L, van Cangh P, Vekemans K, Da Pozzo L, et al. Postoperative radiotherapy after radical prostatectomy: A randomised controlled trial (EORTC trial 22911). Lancet 2005;366:572–8.  Back to cited text no. 65
Agrawal S, Stephenson AJ, Michalski J, Efstathiou JA, Pisansky TM, Feng F, et al. Prostate cancer–specific mortality and survival outcomes for salvage radiation therapy after radical prostatectomy. Int J Radiat Oncol Biol Phys 2016;96:S101.  Back to cited text no. 66
Touijer KA, Karnes RJ, Passoni N, Sjoberg DD, Assel M, Fossati N, et al. Survival outcomes of men with lymph node-positive prostate cancer after radical prostatectomy: A comparative analysis of different postoperative management strategies. Eur Urol 2018;73:890–6.  Back to cited text no. 67
Gupta M, Patel HD, Schwen ZR, Tran PT, Partin AW. Adjuvant radiation with androgen-deprivation therapy for men with lymph node metastases after radical prostatectomy: Identifying men who benefit. BJU Int 2019;123:252–60.  Back to cited text no. 68
Guo L, Zhu Z, Zhang X. Adding radiotherapy to androgen deprivation therapy in men with node-positive prostate cancer after radical prostatectomy: A meta-analysis. Medicine (Baltimore) 2020;99:e19153.  Back to cited text no. 69
Mateo J, Fizazi K, Gillessen S, Heidenreich A, Perez-Lopez R, Oyen WJ, et al. Managing nonmetastatic castration-resistant prostate cancer. Eur Urol 2019;75:285–93.  Back to cited text no. 70
Hövels AM, Heesakkers RA, Adang EM, Jager GJ, Strum S, Hoogeveen YL, et al. The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: A meta-analysis. Clin Radiol 2008;63:387–95.  Back to cited text no. 71
Crawford ED, Stone NN, Yu EY, Koo PJ, Freedland SJ, Slovin SF, et al. Challenges and recommendations for early identification of metastatic disease in prostate cancer. Urology 2014;83:664–9.  Back to cited text no. 72
Crawford ED, Koo PJ, Shore N, Slovin SF, Concepcion RS, Freedland SJ, et al. A clinician's guide to next generation imaging in patients with advanced prostate cancer (RADAR III). J Urol 2019;201:682–92.  Back to cited text no. 73
Zschaeck S, Lohaus F, Beck M, Habl G, Kroeze S, Zamboglou C, et al. PSMA-PET based radiotherapy: A review of initial experiences, survey on current practice and future perspectives. Radiat Oncol 2018;13:90.  Back to cited text no. 74
Aizawa R, Takayama K, Nakamura K, Inoue T, Kobayashi T, Akamatsu S, et al. Long-term outcomes of definitive external-beam radiotherapy for non-metastatic castration-resistant prostate cancer. Int J Clin Oncol 2018;23:749–56.  Back to cited text no. 75
Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med 2018;378:2465–74.  Back to cited text no. 76
Sternberg CN, Fizazi K, Saad F, Shore ND, De Giorgi U, Penson DF, et al. Enzalutamide and survival in nonmetastatic, castration-resistant prostate cancer. N Engl J Med 2020;382:2197–206.  Back to cited text no. 77
Bryant AK, McKay RR, Kader AK, Parsons JK, Einck JP, Kane CJ, et al. Subcastrate testosterone nadir and clinical outcomes in intermediate- or high-risk localized prostate cancer. Int J Radiat Oncol Biol Phys 2019;103:1068–76.  Back to cited text no. 78
Ding M, Lee T, Di Lena R, Shayegan B. Investigating the impact of a lower testosterone threshold on castration-resistant progression in patients on continuous androgen deprivation therapy. J Urol 2019;201:e317–8.  Back to cited text no. 79
Ozyigit G, Hurmuz P, Yuce D, Akyol F. Prognostic significance of castrate testosterone levels for patients with intermediate and high risk prostate cancer. World J Clin Oncol 2019;10:283–92.  Back to cited text no. 80
Weiner AB, Cohen JE, DeLancey JO, Schaeffer EM, Auffenberg GB. Surgical versus medical castration for metastatic prostate cancer: Use and overall survival in a national cohort. J Urol 2020;203:933–9.  Back to cited text no. 81
Sun M, Choueiri TK, Hamnvik O-PR, Preston MA, De Velasco G, Jiang W, et al. Comparison of gonadotropin-releasing hormone agonists and orchiectomy: Effects of androgen-deprivation therapy. JAMA Oncol 2016;2:500–7.  Back to cited text no. 82
Uttley L, Whyte S, Gomersall T, Ren S, Wong R, Chambers D, et al. Degarelix for treating advanced hormone-dependent prostate cancer: An evidence review group perspective of a NICE single technology appraisal. Pharmacoeconomics 2017;35:717–26.  Back to cited text no. 83
Shore ND, Saad F, Cookson MS, George DJ, Saltzstein DR, Tutrone R, et al. Oral relugolix for androgen-deprivation therapy in advanced prostate cancer. N Engl J Med 2020;382:2187–96.  Back to cited text no. 84
Gomella LG. Effective testosterone suppression for prostate cancer: Is there a best castration therapy? Rev Urol 2009;11:52–60.  Back to cited text no. 85
Sweeney CJ, Chen Y-H, Carducci M, Liu G, Jarrard DF, Eisenberger M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 2015;373:737–46.  Back to cited text no. 86
James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet 2016;387:1163–77.  Back to cited text no. 87
Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med 2017;377:352–60.  Back to cited text no. 88
James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP, et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med 2017;377:338–51.  Back to cited text no. 89
Feyerabend S, Saad F, Li T, Ito T, Diels J, Van Sanden S, et al. Survival benefit, disease progression and quality-of-life outcomes of abiraterone acetate plus prednisone versus docetaxel in metastatic hormone-sensitive prostate cancer: A network meta-analysis. Eur J Cancer 2018;103:78–87.  Back to cited text no. 90
Sharma AP, Mavuduru RS, Bora GS, Devana SK, Singh SK, Mandal AK. STAMPEDEing metastatic prostate cancer: CHAARTing the LATITUDEs. Indian J Urol 2018;34:180–4.  Back to cited text no. 91
[PUBMED]  [Full text]  
Chiang CL, So TH, Lam TC, Choi HC. Cost-effectiveness analysis of abiraterone acetate versus docetaxel in the management of metastatic castration-sensitive prostate cancer: Hong Kong's perspective. Prostate Cancer Prostatic Dis 2020;23:108–15.  Back to cited text no. 92
Franke RM, Carducci MA, Rudek MA, Baker SD, Sparreboom A. Castration-dependent pharmacokinetics of docetaxel in patients with prostate cancer. J Clin Oncol 2010;28:4562–7.  Back to cited text no. 93
Kushnir I, Koczka K, Ong M, Canil C, Bossé D, Sabri E, et al. The timing of docetaxel initiation in metastatic castrate-sensitive prostate cancer and the rate of chemotherapy-induced toxicity. Med Oncol 2019;36:18.  Back to cited text no. 94
Shore ND, Antonarakis ES, Cookson MS, Crawford ED, Morgans AK, Albala DM, et al. Optimizing the role of androgen deprivation therapy in advanced prostate cancer: Challenges beyond the guidelines. Prostate 2020;80:527–44.  Back to cited text no. 95
Kyriakopoulos CE, Chen Y-H, Carducci MA, Liu G, Jarrard DF, Hahn NM, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: Long-term survival analysis of the randomized phase III E3805 CHAARTED Trial. J Clin Oncol 2018;36:1080–7.  Back to cited text no. 96
Gravis G, Boher J-M, Chen Y-H, Liu G, Fizazi K, Carducci MA, et al. Burden of metastatic castrate naive prostate cancer patients, to identify men more likely to benefit from early docetaxel: Further analyses of CHAARTED and GETUG-AFU15 studies. Eur Urol 2018;73:847–55.  Back to cited text no. 97
Clarke NW, Ali A, Ingleby FC, Hoyle A, Amos CL, Attard G, et al. Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: Long-term survival results from the STAMPEDE trial. Ann Oncol 2019;30:1992–2003.  Back to cited text no. 98
Hahn AW, Higano CS, Taplin M-E, Ryan CJ, Agarwal N. Metastatic castration-sensitive prostate cancer: Optimizing patient selection and treatment. Am Soc Clin Oncol Educ Book 2018;38:363–71.  Back to cited text no. 99
Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, et al. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med 2019;381:121–31.  Back to cited text no. 100
Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A, et al. ARCHES: A randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol 2019;37:2974–86.  Back to cited text no. 101
Parker DC, Cookson MS. The changing landscape in the management of newly diagnosed castration sensitive metastatic prostate cancer. Investig Clin Urol 2020;61:S3–7.  Back to cited text no. 102
Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): A randomised controlled phase 3 trial. Lancet 2018;392:2353–66.  Back to cited text no. 103
Boevé LMS, Hulshof MC, Vis AN, Zwinderman AH, Twisk JW, Witjes WP, et al. Effect on survival of androgen deprivation therapy alone compared to androgen deprivation therapy combined with concurrent radiation therapy to the prostate in patients with primary bone metastatic prostate cancer in a prospective randomised clinical trial: Data from the HORRAD Trial. Eur Urol 2019;75:410–8.  Back to cited text no. 104
Burdett S, Boevé LM, Ingleby FC, Fisher DJ, Rydzewska LH, Vale CL, et al. Prostate radiotherapy for metastatic hormone-sensitive prostate cancer: A STOPCAP systematic review and meta-analysis. Eur Urol 2019;76:115–24.  Back to cited text no. 105
Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, et al. Trial design and objectives for castration-resistant prostate cancer: Updated recommendations from the prostate cancer clinical trials working group 3. J Clin Oncol 2016;34:1402–18.  Back to cited text no. 106
Sella A, Sternberg CN, Skoneczna I, Kovel S. Prostate-specific antigen flare phenomenon with docetaxel-based chemotherapy in patients with androgen-independent prostate cancer. BJU Int 2008;102:1607–9.  Back to cited text no. 107
de Morrée ES, Vogelzang NJ, Petrylak DP, Budnik N, Wiechno PJ, Sternberg CN, et al. Association of survival benefit with docetaxel in prostate cancer and total number of cycles administered: A post hoc analysis of the mainsail study. JAMA Oncol 2017;3:68–75.  Back to cited text no. 108
Shen Y-C, Chiang P-H, Luo H-L, Chuang Y-C, Chen Y-T, Kang C-H, et al. Determine of the optimal number of cycles of docetaxel in the treatment of metastatic castration-resistant prostate cancer. Kaohsiung J Med Sci 2016;32:458–63.  Back to cited text no. 109
de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels J-P, Kocak I, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: A randomised open-label trial. Lancet 2010;376:1147–54.  Back to cited text no. 110
Eisenberger M, Hardy-Bessard A-C, Kim CS, Géczi L, Ford D, Mourey L, et al. Phase III study comparing a reduced dose of cabazitaxel (20 mg/m2) and the currently approved dose (25 mg/m2) in postdocetaxel patients with metastatic castration-resistant prostate cancer-PROSELICA. J Clin Oncol 2017;35:3198–206.  Back to cited text no. 111
Noronha V, Joshi A, Prabhash K. Beyond ten cycles of cabazitaxel for castrate-resistant prostate cancer. Indian J Cancer 2014;51:363–5.  Back to cited text no. 112
[PUBMED]  [Full text]  
de Wit R, de Bono J, Sternberg CN, Fizazi K, Tombal B, Wülfing C, et al. Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer. N Engl J Med 2019;381:2506–18.  Back to cited text no. 113
Perumal Kalaiyarasi J, Radhakrishnan V, Ganesan T, Raja A, Ganesan P, Dhanushkodi M, et al. Experience with using fosfestrol for treating metastatic castrate-resistant prostate cancer in resource-limited setting. Indian J Med Paediatr Oncol 2019;40:79.  Back to cited text no. 114
Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fosså SD, et al. Alpha emitter Radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369:213–23.  Back to cited text no. 115
Choudhury PS, Gupta M. Theranostics in India: A particularly exquisite concept or an experimental tool. Nucl Med Mol Imaging 2019;53:92–5.  Back to cited text no. 116
Khalaf DJ, Annala M, Taavitsainen S, Finch DL, Oja C, Vergidis J, et al. Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: A multicentre, randomised, open-label, phase 2, crossover trial. Lancet Oncol 2019;20:1730–9.  Back to cited text no. 117
Andrews JR, Ahmed ME, Karnes RJ, Kwon E, Bryce AH. Systemic treatment for metastatic castrate resistant prostate cancer: Does seqence matter? Prostate 2020;80:399–406.  Back to cited text no. 118
Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: Treatment of relapsing, metastatic, and castration-resistant prostate cancer. Eur Urol 2017;71:630–42.  Back to cited text no. 119
Bubendorf L, Schöpfer A, Wagner U, Sauter G, Moch H, Willi N, et al. Metastatic patterns of prostate cancer: An autopsy study of 1,589 patients. Hum Pathol 2000;31:578–83.  Back to cited text no. 120
Jakob T, Tesfamariam YM, Macherey S, Kuhr K, Adams A, Monsef I, et al. Bisphosphonates or RANK-ligand-inhibitors for men with prostate cancer and bone metastases: A network meta-analysis. Cochrane Database Syst Rev 2020;12:CD013020.  Back to cited text no. 121
Miller K, Steger GG, Niepel D, Lüftner D. Harnessing the potential of therapeutic agents to safeguard bone health in prostate cancer. Prostate Cancer Prostatic Dis 2018;21:461–72.  Back to cited text no. 122
Smith MR, Halabi S, Ryan CJ, Hussain A, Vogelzang N, Stadler W, et al. Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: Results of CALGB 90202 (alliance). J Clin Oncol 2014;32:1143–50.  Back to cited text no. 123
Kamba T, Kamoto T, Maruo S, Kikuchi T, Shimizu Y, Namiki S, et al. A phase III multicenter, randomized, controlled study of combined androgen blockade with versus without zoledronic acid in prostate cancer patients with metastatic bone disease: Results of the ZAPCA trial. Int J Clin Oncol 2017;22:166–73.  Back to cited text no. 124
Saad F, Shore N, Van Poppel H, Rathkopf DE, Smith MR, de Bono JS, et al. Impact of bone-targeted therapies in chemotherapy-naïve metastatic castration-resistant prostate cancer patients treated with abiraterone acetate: Post hoc analysis of study COU-AA-302. Eur Urol 2015;68:570–7.  Back to cited text no. 125
Saad F, Carles J, Gillessen S, Heinrich D, Gratt J, Miller K, et al. Radium-223 in an international early access program (EAP): Effects of concomitant medication on overall survival in metastatic castration-resistant prostate cancer (mCRCP) patients. JCO 2015;33:5034. doi: 10.1200/jco. 2015.33.15_suppl. 5034.  Back to cited text no. 126
Sartor O, Coleman R, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, et al. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: Results from a phase 3, double-blind, randomised trial. Lancet Oncol 2014;15:738–46.  Back to cited text no. 127


  [Figure 1]

  [Table 1], [Table 2], [Table 3]


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