Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with prostate cancer



# Introduction
In 2020 an estimated 19.3 million new cases of cancer were diagnosed and almost 10 million cancer-related deaths recorded, worldwide. [bib_ref] Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for..., Sung [/bib_ref] Of these, prostate cancer accounted for 7.3% (1 414 259) of new cases and 3.8% (375 304) of cancer deaths, representing 14.5% of new cases of cancer and 6.8% of cancer deaths in men worldwide. Prostate cancer is the second most frequently diagnosed cancer in men after lung cancer and the fifth most common cause of cancer death worldwide. [bib_ref] Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for..., Sung [/bib_ref] Asia historically has been considered to have a low incidence of prostate cancer, but the incidence of and mortality from prostate cancer is increasing rapidly. [bib_ref] Epidemiology and genomics of prostate cancer in Asian men, Zhu [/bib_ref] However, the age-standardised rates for prostate cancer incidence in Western Asia, South-Eastern Asia and South-Central Asia were 28.6, 13.5 and 6.3 per 100 000 men, respectively, in 2020, compared with 73 per 100 000 for North America. [bib_ref] Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for..., Sung [/bib_ref] Both the incidence as well as the mortalityto-incidence ratio are associated with the human development index. [bib_ref] Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for..., Sung [/bib_ref] The lower incidence of prostate cancer in Asian men compared with Western men may also be due to less prostate-specific antigen (PSA) screening. Studies in both Japan [bib_ref] Prostate-specific antigen-based population screening for prostate cancer: current status in Japan and..., Kitagawa [/bib_ref] and Taiwan [bib_ref] Increasing incidence of prostate cancer in Taiwan: a study of related factors..., Lin [/bib_ref] have shown the incidence of prostate cancer to increase with PSA testing. In the case of the Japanese study, [bib_ref] Prostate-specific antigen-based population screening for prostate cancer: current status in Japan and..., Kitagawa [/bib_ref] PSA screening was associated with a reduction in the proportion of advanced prostate cancers detected. However, another reason for the difference in the incidence of prostate cancer may be due to the fact that the genomic features of prostate cancer differ between Asian and Western populations and also vary between different regions and countries in Asia. [bib_ref] Epidemiology and genomics of prostate cancer in Asian men, Zhu [/bib_ref] A recent study has shown the Han Chinese, Korean and Japanese populations to have distinct genetic profiles. [bib_ref] Genetic structure, divergence and admixture of Han Chinese, Japanese and Korean populations, Wang [/bib_ref] Asian studies have also shown men with diabetes to be at a higher risk of developing prostate cancer than their non-diabetic counterparts. [bib_ref] History of diabetes mellitus and the risk of prostate cancer: the Ohsaki..., Li [/bib_ref] [bib_ref] The association of diabetes mellitus with liver, colon, lung, and prostate cancer..., Lee [/bib_ref] [bib_ref] Prostate cancer mortality in Taiwanese men: increasing age-standardized trend in general population..., Tseng [/bib_ref] [bib_ref] Diabetes and risk of prostate cancer: a study using the National Health..., Tseng [/bib_ref] Thus, differences in genetics, environment, lifestyle, diet and culture are all likely to influence the management of prostate cancer in Asia, as demonstrated by a comparison of the epidemiology, incidence, mortality and risk factors for prostate cancer in Eastern Asia, South-Eastern Asia and South-Central Asia with those for Western countries. [bib_ref] The incidence, mortality and risk factors of prostate cancer in Asian men, Chung [/bib_ref] Guidelines and recommendations for the treatment and management of patients with prostate/advanced prostate cancer in Asia have been published for the Asia Pacific region, [bib_ref] Management of patients with advanced prostate cancer in the Asia Pacific region:..., Chiong [/bib_ref] China,Japan, [bib_ref] NCCN Asia Consensus Statement prostate cancer, Hinotsu [/bib_ref] [bib_ref] Evidenced-based clinical practice guideline for prostate cancer (summary: Japanese Urological Association, 2016..., Kakehi [/bib_ref] India, [bib_ref] Expert Group consensus opinion on prostate cancer diagnosis and management in India..., Ghose [/bib_ref] [bib_ref] Prostate cancer research in India: a scientometric analysis of publications output during..., Gupta [/bib_ref] Korea, [bib_ref] Korean guidelines for the management of metastatic prostate cancer, Kim [/bib_ref] Singapore [bib_ref] Guidelines on management of prostate cancer, Sim [/bib_ref] and Taiwanand are important for the standardisation of both diagnostic and treatment approaches, with the aim of optimising clinical outcomes for what is an increasing health care problem in Asia. The European Society for Medical Oncology (ESMO) guidelines for the diagnosis, treatment and follow-up of patients with prostate cancer were published in 2020, [bib_ref] Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Parker [/bib_ref] and a decision was taken by ESMO and the Singapore Society of Oncology (SSO) that these guidelines should be adapted for patients of Asian ethnicity.
Consequently, representatives of SSO, ESMO, the Chinese Society of Clinical Oncology (CSCO), the Indian Society of Medical and Paediatric Oncology (ISMPO), the Japanese Society of Medical Oncology (JSMO), the Korean Society for Medical Oncology (KSMO), the Malaysian Oncological Society (MOS) and the Taiwan Oncology Society (TOS) convened for a virtual, 'face-to-face', working meeting on 20 November 2021, hosted by SSO, to adapt the recent ESMO Clinical Practice Guidelines for patients with prostate cancer. This manuscript summarises the Pan-Asian adapted guidelines, developed before and finalised during the meeting, accompanied by the level of evidence (LoE), grade of recommendation (GoR) and percentage consensus reached for each recommendation. The main focus was on the scientific acceptability of each recommendation, independent of the availability, reimbursement and practical challenges that may be associated with it, in certain Asian countries.

# Methodology
This Pan-Asian adaptation of the current ESMO Clinical Practice Guidelines for prostate cancer, [bib_ref] Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Parker [/bib_ref] together with any relevant data updates from the ESMO 2021 Annual Meeting, was prepared in accordance with the principles of ESMO standard operating procedures (http://www.esmo. org/Guidelines/ESMO-Guidelines-Methodology) and was an SSOeESMO initiative endorsed by CSCO, ISMPO, JSMO, KSMO, MOS and TOS.
An international panel of experts was selected from the SSO (n 14 6), the ESMO (n 14 5) and two experts from each of the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS) and Taiwan (TOS). Only two of the six expert members from the SSO (AW and MLKC) were allowed to vote on the recommendations together with the experts from each of the six other Asian oncology societies (n 14 14). Of the 14 voting experts, 4 were urologists [YZ (CSCO), QZ (CSCO), YSP (TOS) and HK (JSMO)] and the remainder oncologists.
A modified Delphi process was used to review, accept or adapt each of the individual recommendations in the latest ESMO Clinical Practice Guidelines. [bib_ref] Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Parker [/bib_ref] The 14 Asian experts were asked to vote YES or NO (one vote per society) on the 'acceptability' (agreement with the scientific content of the recommendation) and 'applicability' (availability, reimbursement and practical challenges) of each of the ESMO recommendations in a pre-meeting survey (see Supplementary Methodology, available at https://doi.org/10.1016/j.esmoop. 2022.100518). For recommendations, where a consensus was not reached, the Asian experts were invited to modify the wording of the recommendation(s) at the 'face-to-face' virtual meeting using rounds of voting in order to determine the definitive acceptance or rejection of an adapted recommendation and discuss the applicability challenges. The 'Infectious Diseases Society of America-United States Public Health Service Grading System' (Supplementary [fig_ref] Table 1: Summary of Asian recommendations mpMRI should be used to confirm the indication... [/fig_ref] , available at https://doi.org/10.1016/j.esmoop. 2022.100518) [bib_ref] Summary of the guidelines for preventing opportunistic infections among hematopoietic stem cell..., Dykewicz [/bib_ref] was used to define the LoE and strength (grade) of each recommendation. Any modifications to the initial recommendations were highlighted in bold text in a summary table of the final Asian recommendations and in the main text, if and as applicable. A consensus was considered to have been achieved when !80% of experts voted that a recommendation was acceptable.

# Results
In the initial pre-meeting survey, the 14 Asian experts reported on the 'acceptability' and 'applicability' of the 50 recommendations for the diagnosis, treatment and followup of patients with prostate cancer based on the most recent ESMO Clinical Practice Guidelines 20 A lack of agreement (no consensus) in the pre-meeting survey was established for 'recommendations 2b and c, 6a, 12a and 13c', in terms of 'acceptability', leading to their discussion during the 'face-to-face' meeting. In addition, no consensus was established for 'recommendations 1b, 2a-d, 6a, 7d, 8a, 10a, 11a, 12a-d, 13c and 14b' in terms of 'applicability' , available at https://doi.org/10.1016/j.esmoop.2022.100518). Of the latter, three recommendations ('recommendations 7d, 12b and 14b') were discussed due to the fact that comments relating to scientific acceptability were made under applicability. A further three recommendations ('recommendations 4f, 5b and 9a') needed to be updated and two new recommendations ('recommendations 11g and 12e') added due to the emergence of new data.
For the purposes of these guidelines, the following general definitions apply:
Early prostate cancerdlocalised prostate cancer without evidence of lymph node involvement or distant metastases.
Locally advanced prostate cancerd!T3b prostate cancer with or without lymph node involvement within the pelvis.
Metastatic prostate cancerdprostate cancer with lymph node invasion beyond the pelvis and/or bone or visceral spread.
Castration-resistant prostate cancerdprostate cancer that no longer responds to androgen deprivation therapy (ADT) despite adequate castration evidenced by serum testosterone levels <0.50 ng/ml; typically, three consecutive rises in PSA >0.2 ng/ml.
The majority of prostate cancers are adenocarcinomas, and for the purposes of this guidelines manuscript, the term prostate cancer refers to adenocarcinomas, unless otherwise specified. 1. Screening and early detectiondrecommendations 1a-c In Western countries, population-based screening of middle-aged men using PSA testing has increased early diagnosis and decreased prostate cancer mortality. [bib_ref] Screening and prostate cancer mortality: results of the European Randomised Study of..., Schroder [/bib_ref] [bib_ref] Strategy for detection of prostate cancer based on relation between prostate specific..., Vickers [/bib_ref] [bib_ref] Recent trends in prostate cancer mortality show a continuous decrease in several..., Bouchardy [/bib_ref] Although a meta-analysis of data from five randomised controlled trials (RCTs) showed PSA testing not to decrease prostate cancer mortality, [bib_ref] Screening for prostate cancer, Ilic [/bib_ref] the European Randomised Study of Screening for Prostate Cancer (ERSPC) reported a significant 27% reduction in prostate cancer-specific mortality in men aged between 55 and 69 years, after 13 years of follow-up. [bib_ref] Screening and prostate cancer mortality: results of the European Randomised Study of..., Schroder [/bib_ref] As a consequence, the American (AUA) and European (EAU) Urological Associations state, respectively, that well-informed men aged 55-69 years cannot be denied PSA testing [bib_ref] Early detection of prostate cancer: AUA Guideline, Carter [/bib_ref] and that PSA testing should be offered to wellinformed men aged >50 years with a life expectancy of at least 10-15 years. [bib_ref] EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment..., Heidenreich [/bib_ref] The Japanese Urological Association (JUA) recommends PSA-based screening.However, in Asia, the level of PSA testing is low compared with Western countries. Despite this, the Pan-Asian panel of experts agreed with and accepted completely (100% consensus) the ESMO recommendations on Screening and early detection, 'recommendations 1a-c' below and [fig_ref] Table 1: Summary of Asian recommendations mpMRI should be used to confirm the indication... [/fig_ref]. However, in terms of applicability, 'recommendation 1b' is not yet implemented in 

## Diagnosis and pathologydrecommendations 2a-d
The risk of being diagnosed with and developing clinically significant prostate cancer is related to age, ethnicity, family history, PSA level, free/total PSA ratio and findings on digital rectal examination. [bib_ref] Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial, Thompson [/bib_ref] Physicians are encouraged to consider these factors for risk calculations. Until recently, transrectal (TR) ultrasound-guided prostate biopsy was the standard for detecting prostate cancer in patients with elevated PSA levels. However, several studies suggest that multi-parametric magnetic resonance imaging (mpMRI) should be carried out before biopsy, 30-32 including a systematic review and meta-analysis of mpMRI for the diagnosis of prostate cancer conducted in China, [bib_ref] Accuracy of multiparametric magnetic resonance imaging for diagnosing prostate Cancer: a systematic..., Zhen [/bib_ref] which showed mpMRI to be a sensitive tool for the diagnosis and detection of prostate cancer. According to the ESMO guidelines, 20 when mpMRI is positive [i.e. Prostate ImagingeReporting and Data System (PI-RADS) !3], a targeted biopsy, plus or minus systematic biopsies, should be carried out. When mpMRI is negative (i.e. PI-RADS 2), and clinical suspicion of prostate cancer is low, the biopsy can be omitted in well-informed patients. An algorithm for the diagnostic work-up and staging of prostate cancer, taken from the ESMO guidelines, 20 is presented in . In addition, a Korean study has shown biparametric magnetic resonance imaging (bpMRI) to have similar efficacy to mpMRI in the detection of prostate cancer and clinically significant prostate cancer. [bib_ref] Comparison of multiparametric and biparametric MRI in first round cognitive targeted prostate..., Lee [/bib_ref] More recently, comparison of bpMRI with mpMRI in combination with PSA density (PSAD) in the detection of clinically significant prostate cancer showed bpMRI combined with PSAD to achieve a better detection rate than mpMRI in Asian patients. [bib_ref] MRI combined with PSA density in detecting clinically significant prostate cancer in..., Han [/bib_ref] Diffusionweighted imaging as part of mpMRI techniques has recently been investigated in a Japanese study for the detection of clinically significant prostate cancer in patients with elevated PSA levels, [bib_ref] Diffusion-weighted imaging in prostate cancer, Tamada [/bib_ref] and further refinement to the use of these techniques in Asia is likely to be forthcoming.
Thus, the Pan-Asian experts agreed with and 'accepted' completely (100% consensus) the ESMO 'recommendation 2a' below without change, although in terms of 'applicability' MRI may not be available/reimbursed in some Asian countries (see However, there was considerable discussion around ESMO 'recommendations 2b and c' with a lack of consensus in terms of acceptability and applicability in the premeeting survey , available at https://doi.org/10.1016/j.esmoop.2022.100518).
Prostate cancer risk calculation tools provide quantitative guidance for decision making regarding whether or not to carry out a biopsy. It was emphasised during discussions Transperineal prostate (TP) biopsy is emerging as one of the options for prostate cancer diagnosis, and when compared with TR prostate biopsy it offers a non-inferior cancer detection rate, [bib_ref] Transperineal prostate biopsy: the modern gold standard to prostate cancer diagnosis, Ortner [/bib_ref] with a lower infection rate. A systematic comparison of TR and TP prostate biopsies in terms of efficacy and complications in the detection of prostate cancer in Asian studies showed no significant difference in prostate cancer detection rate and complications between the TR and TP approaches, [bib_ref] The results of transperineal versus transrectal prostate biopsy: a systematic review and..., Shen [/bib_ref] [bib_ref] Comparison between transrectal and transperineal prostate biopsy for detection of prostate cancer:..., Xue [/bib_ref] with the TP approach shown, in a meta-analysis conducted in China, to have a lower risk of fever and rectal bleeding. [bib_ref] Transperineal versus transrectal prostate biopsy in the diagnosis of prostate cancer: a..., Xiang [/bib_ref] Thus, in the case of 'recommendation 2c' below, the original text was revised for the sake of clarification (with the changes highlighted in bold text below and [fig_ref] Table 1: Summary of Asian recommendations mpMRI should be used to confirm the indication... [/fig_ref] 

## Staging and risk assessmentdrecommendations 3a-c
Patients should be assessed with regard to their general health and comorbidities, and those who are not suitable for treatment with curative intent, by virtue of poor general health, do not normally require staging investigations. MRI provides tumour staging information. [bib_ref] The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge..., Amin [/bib_ref] The Gleason score is recommended for pathological grading of prostate adenocarcinomas and comprises a system of primary and secondary scores. [bib_ref] Grading of prostate cancer: a work in progress, Kweldam [/bib_ref] The degree of differentiation is defined/ determined by the sum of the two scores. Thus, patients with localised disease can be classified as outlined in [bib_ref] Meta-analysis of (11)C-choline and (18)Fcholine PET/CT for management of patients with prostate..., Von Eyben [/bib_ref] or the emerging prostate-specific membrane antigen (PSMA)-PETeCT. Gallium PSMA-PETeCT has been shown to have value as a diagnostic and clinical decisionmaking tool in Asian patients with rapid biochemical recurrence. [bib_ref] 68 Gallium-labelled PSMA-PET/CT as a diagnostic and clinical decision-making tool in Asian..., Tan [/bib_ref]. Where possible, patients should be treated within a multidisciplinary team environment which should include both urologists and radiation oncologists as well as medical oncologists. Prostate cancer can be slow growing and may never cause patients any problems during their lifetime. Thus, 'watchful waiting' is an option for those patients with other health problems who may be unsuitable for or unwilling to undergo treatment with curative intent such as surgery [bib_ref] Radical prostatectomy or watchful waiting in prostate cancer -29-year follow-up, Bill-Axelson [/bib_ref] [bib_ref] Radical prostatectomy versus observation for localized prostate cancer, Wilt [/bib_ref] or radiotherapy (RT). It generally applies to patients with shorter life expectancies (<10 years). Active surveillance, on the other hand, involves careful patient monitoring such as PSA testing, repeat biopsies and MRI, to avoid patients having unnecessary treatment, and is for patients with slow-growing tumours who would benefit from curative treatment if required. [bib_ref] Guidelines on management of prostate cancer, Sim [/bib_ref] [bib_ref] Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Parker [/bib_ref] Curative options for these low-risk patients include external beam RT (EBRT), low-dose rate brachytherapy and radical prostatectomy (RP) [bib_ref] Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Parker [/bib_ref] improve survival over RT alone [bib_ref] Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer:..., Warde [/bib_ref] [bib_ref] Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/..., Widmark [/bib_ref] [bib_ref] Recent trend of androgen deprivation therapy in newly diagnosed prostate cancer patients:..., Lim [/bib_ref] [fig_ref] Figure 3: High-risk localised and locally advanced prostate cancer treatment algorithm [/fig_ref]. More recently, combination therapy with abiraterone acetate plus prednisone/prednisolone (AAP) has been shown to be associated with significantly higher rates of metastasis-free survival compared with ADT alone in patients with high-risk localised disease meeting the STAMPEDE trial criteria. [bib_ref] Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate..., Attard [/bib_ref] RP plus pelvic lymphadenectomy is also an option for high-risk disease [bib_ref] Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Parker [/bib_ref] [fig_ref] Figure 3: High-risk localised and locally advanced prostate cancer treatment algorithm [/fig_ref] and Supplementary For patients relapsing after RT, local salvage using highintensity focused ultrasound (HIFU), high-dose rate brachytherapy or RP may be required. Observation with delayed ADT may be appropriate for those patients with biochemical relapse and symptomatic local disease, proven metastases or a PSA doubling time of <3 months [fig_ref] Figure 3: High-risk localised and locally advanced prostate cancer treatment algorithm [/fig_ref] , and also Section 8 below.). For those patients who have undergone RP, RT to the prostate bed plus or minus pelvic nodes may be required or observation with delayed ADT [fig_ref] Figure 3: High-risk localised and locally advanced prostate cancer treatment algorithm [/fig_ref]. These patients, however, often require postoperative RT plus or minus ADT.
All the Asian experts agreed completely with 'recommendations 4a and b' below, in terms of acceptability (100% consensus) and applicability, without change. 4a. Watchful waiting with delayed ADT is an option for patients with localised or locally advanced disease who are not suitable for, or unwilling to have, radical treatment [bib_ref] United in Fight against prOstate cancer (UFO) registry: first results from a..., Uemura [/bib_ref] All the Asian experts accepted completely (100% consensus) 'recommendations 4d-f and 4h' below, in the pre-meeting survey without change. However, 'recommendation 4f' was updated at the virtual 'face-to-face' meeting and a new recommendation 4g added (as denoted by the bold text below and in [fig_ref] Table 1: Summary of Asian recommendations mpMRI should be used to confirm the indication... [/fig_ref] 

## Relapse after radical therapy
Salvage RT to prostate bed +/-pelvic nodes Consider ADT for 6 months or bicalutamide for 2 years

## Esmo open
4h. RP plus pelvic lymphadenectomy is an option for selected men with high-risk disease [bib_ref] Outcomes of pathologically localized high-grade prostate cancer treated with radical prostatectomy, Heo [/bib_ref] [bib_ref] Comparison of clinical outcomes of radical prostatectomy versus IMRT with long-term hormone..., Shih [/bib_ref] [III, B].

## Neoadjuvant and adjuvant hormone treatmentd recommendations 5a-c
The benefit of neoadjuvant and concurrent ADT together with RT has been established in RCTs 67,68 for men with highrisk localised and locally advanced prostate cancer. [bib_ref] Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Parker [/bib_ref] Furthermore, RCTs in patients with unfavourable intermediate-risk prostate cancer risk [primary Gleason score 4, !50% positive biopsy scores or !2 intermediaterisk factors (cT2b-c, Gleason score 7, PSA 10-20 ng/ml)], and therefore an anticipated poorer outcome, showed longcourse (18-36 months) adjuvant ADT after RT to improve overall survival in those patients. [bib_ref] Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of..., Bolla [/bib_ref] [bib_ref] Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction..., Hanks [/bib_ref] [bib_ref] Duration of androgen deprivation therapy in high-risk prostate cancer: a randomized phase..., Nabid [/bib_ref] All the Asian experts agreed completely with 'recommendations 5a and b' below in terms of both acceptability (100% consensus) and applicability in the pre-meeting survey. However, as for 'recommendation 4f' above, new data from the phase III STAMPEDE trial [bib_ref] Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate..., Attard [/bib_ref] showing the addition of 2 years of AAP to improve both metastases-free survival (P 14 3.2 A 10 A7 ) and overall survival (P 14 0.0005) in patients with very-high-risk M0 disease also necessitated an update to 'recommendation 5b', and a new recommendation 5c added (as denoted by the bold text below and in [fig_ref] Table 1: Summary of Asian recommendations mpMRI should be used to confirm the indication... [/fig_ref] 7. Post-operative RTdrecommendations 7a-e RT can be administered post-operatively as either adjuvant or salvage therapy, 20 but it is unclear which is more appropriate for patients with localised or locally advanced prostate cancer following RP. Adjuvant RT (ART) had been shown to improve biochemical control but not overall survival. [bib_ref] Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy..., Wiegel [/bib_ref] A prospectively planned, systematic review and meta-analysis of event-free survival (EFS) data for 2153 patients from three trials comparing immediate ART (n 14 1075) with early salvage RT (SRT, n 14 1078) (the ARTISTIC collaboration) [bib_ref] Adjuvant or early salvage radiotherapy for the treatment of localised and locally..., Vale [/bib_ref] showed no evidence that ART improved EFS over SRT (HR 0.95; 95% CI 0.75-1.21; P 14 0.70). ART was associated with bladder and bowel morbidity but not with any proven benefit in terms of biochemical progression-free survival (PFS). Thus, observation followed by SRT in the case of PSA failure is the current standard in Europe and Asia after RP, with better outcomes achieved when a patient's PSA is <0.5 ng/ml. [bib_ref] Prognostic value of biochemical recurrence following treatment with curative intent for prostate..., Van Den Broeck [/bib_ref] [bib_ref] Outcomes and prediction models for exclusive prostate bed salvage radiotherapy among patients..., Tseng [/bib_ref] ART may be offered to selected patients with positive resection margins or extracapsular extension. [bib_ref] Systematic review and meta-analysis of trials evaluating the role of adjuvant radiation..., Bhindi [/bib_ref] Comparison of SRT with SRT plus either 6 months of ADT or 24 months of bicalutamide showed 24 months of bicalutamide to reduce the rate of prostate cancer death (HR 0.77; 95% CI 0.59-0.99; P 14 0.04) and improve overall survival (HR 0.49; 95% CI 0.32-0.73; P < 0.001). [bib_ref] Radiation with or without antiandrogen therapy in recurrent prostate cancer, Shipley [/bib_ref] The randomised phase III GETUG-AFU 16 trial showed ADT to improve metastasis-free survival (HR 0.73; 95% CI 0.54-0.98; P 14 0.034), but not overall survival. [bib_ref] Interest of short hormonotherapy (HT) associated with radiotherapy (RT) as salvage treatment..., Carrie [/bib_ref] In a United States study, comparison of pelvic node RT plus 6 months of ADT with prostate bed-only RT or prostate bed RT plus 6 months of ADT showed the addition of pelvic RT to improve freedom from failure and freedom from metastases compared with prostate bed-only RT (HR 0.52; 95% CI 0.30-0.92; P 14 0.014). [bib_ref] Short term androgen deprivation therapy without or with pelvic lymph node treatment..., Pollack [/bib_ref] Thus, all the Asian experts accepted completely (100% consensus) 'recommendations 7a-e' below. some Asian countries, ADT is not routinely offered following salvage RT, as patients are referred for early salvage RT when their PSA levels are <1.0 ng/ml, and the benefit of ADT in these patients is less certain.

## Treatment of relapse after radical local treatmentdrecommendations 8a-d
For patients with biochemically recurrent prostate cancer, PSMA-PET imaging is replacing conventional imaging, based on its superior sensitivity and specificity, in terms of diagnosis. [bib_ref] Gallium-68 prostate-specific membrane antigen positron emission tomography in advanced prostate cancer-updated diagnostic..., Perera [/bib_ref] There are three treatment approaches for patients who relapse after radical local treatment and these are (i) local salvage therapy, (ii) metastasis-directed therapy and (iii) systemic therapy. [bib_ref] Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Parker [/bib_ref] Since the natural history of PSA recurrence following treatment is long, life expectancy needs to be taken into account when considering local treatment options. [bib_ref] Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Parker [/bib_ref] In the case of patients with local recurrence, in the absence of metastases, the local treatment options in Europe include salvage RP, HIFU, cryoablation and brachytherapy, and typically only provide temporary control.
Early detection of recurrence theoretically provides the opportunity to selectively ablate metastases with the possibility of prolonging survival. Recently, a European trial has shown metastasis-directed therapy to improve biochemical progression and the time to palliative ADT, [bib_ref] Surveillance or metastasisdirected therapy for oligometastatic prostate cancer recurrence: a prospective, randomized,..., Ost [/bib_ref] while another trial conducted in Canada, the Netherlands, Scotland and Australia, in different solid tumour types (of which 16% were prostate cancer) showed the addition of stereotactic body RT to standard of care to improve overall survival. [bib_ref] Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with..., Palma [/bib_ref] Systemic ADT is not routinely recommended for patients with biochemical relapse unless they have a rapid PSA doubling time, symptomatic local disease or proven metastases. Early administration of ADT has been shown to confer no survival benefit [bib_ref] Systematic review of the diagnosis and management of malignant extradural spinal cord..., Loblaw [/bib_ref] and is associated with an adverse effect on quality of life. [bib_ref] Timing of androgendeprivation therapy in patients with prostate cancer with a rising..., Duchesne [/bib_ref] Intermittent ADT when compared with continuous ADT had a more favourable toxicity profile with no difference in overall survival (HR 1.02; 95% CI 0.86-1.21). [bib_ref] Intermittent androgen suppression for rising PSA level after radiotherapy, Crook [/bib_ref] Thus, all the Asian experts accepted completely (100% consensus) 'recommendations 8a-d' below, with a revision to the text of 'recommendation 8b' for clarification. 8a. For patients with a local recurrence following RP and no distant metastases, the pros and cons of local salvage therapy should be discussed, taking into account life expectancy and the long natural history of isolated local recurrences [III, C]. 8b. Patients with biochemical relapse after radical RT who may be candidates for local salvage or metastasisdirected treatment should undergo imaging with next generation imaging tools such as [bib_ref] Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate..., Roach M 3rd [/bib_ref] to ADT. This benefit was seen particularly in M1 patients, in combination with ADT, and also in combination with zoledronic acid, in the STAMPEDE trial, [bib_ref] Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy..., James [/bib_ref] and in patients with high-volume disease in the CHAARTED trial. [bib_ref] Chemohormonal therapy in metastatic hormone-sensitive prostate cancer, Sweeney [/bib_ref] The GETUG-AFU 15 trial showed docetaxel (75 mg/m 2 every 21 days for 9 cycles) added to ADT to improve PSA PFS and radiographic PFS but not overall survival. However, a metaanalysis of the data from these three trials confirmed the benefit of the addition of docetaxel to ADT regardless of disease volume (HR 0.77; 95% CI 0.68-0.87). [bib_ref] Docetaxel versus surveillance after radical radiotherapy for intermediate-or high-risk prostate cancer-results from..., Kellokumpu-Lehtinen [/bib_ref] [bib_ref] Addition of docetaxel or bisphosphonates to standard of care in men with..., Vale [/bib_ref] The benefit of the addition of AAP to ADT was demonstrated in the randomised phase III LATITUDE trial, 97 a subgroup analysis of the LATITUDE trial in Japanese patients [bib_ref] Efficacy and safety of abiraterone acetate plus prednisone in Japanese patients with..., Fukasawa [/bib_ref] and in the STAMPEDE 99 trial. However, recent data from the phase III PEACE-1 trial showed the addition of AAP to ADT plus docetaxel to improve both radiographic PFS (HR 0.50; 99.9% CI 0.34-0.71; P < 0.0001) and overall survival (HR 0.75; 95% CI 0.59-0.95; P 14 0.017). In patients with high-volume disease (at least four bone metastases including at least one in the peripheral skeleton, or visceral metastasis), the survival medians were 5.14 and 3.47 years, respectively, for those patients receiving abiraterone versus those receiving docetaxel ADT (HR 0.72; 95% CI 0.55-0.95; P 14 0.019). [bib_ref] Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de..., Fizazi [/bib_ref] The randomised phase III TITAN trial showed the addition of apalutamide to ADT to improve overall survival in patients with mHNPC. [bib_ref] Apalutamide for metastatic, castration-sensitive prostate cancer, Chi [/bib_ref] The benefit of adding enzalutamide to ADT for the treatment of patients with mHNPC has been shown in the phase III ARCHES 102 and ENZAMET 103 trials. The randomised HORRAD [bib_ref] Effect on survival of androgen deprivation therapy alone compared to androgen deprivation..., Boeve [/bib_ref] and STAMPEDE 105 trials have compared ADT alone (docetaxel was allowed in addition to ADT in both arms of the STAMPEDE trial) or in combination with RT to the prostate in patients with mHNPC. RT improved time to PSA progression in the HORRAD trial, [bib_ref] Effect on survival of androgen deprivation therapy alone compared to androgen deprivation..., Boeve [/bib_ref] and time to treatment failure in the STAMPEDE trial. [bib_ref] Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE):..., Parker [/bib_ref] The Asian experts agreed and accepted completely 'recommendations 9a-d' in the pre-meeting survey The treatment recommendations for mHNPC are presented in [fig_ref] Figure 4: Metastatic prostate cancer treatment algorithm [/fig_ref].

## Non-metastatic castration-resistant prostate cancerd recommendation 10a
According to the EAU-ESTRO-SIOG guidelines, patients are classified as castration-resistant if their disease progresses during ADT with serum testosterone at castrate levels. [bib_ref] EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: treatment of relapsing, metastatic, and..., Cornford [/bib_ref] The phase III SPARTAN trial has shown apalutamide to significantly increase median metastasis-free survival (40.5 versus 16.2 months, HR 0.28; 95% CI 0.23-0.35) and time to symptomatic progression (HR 0.45; 95% CI 0.32-0.63) when compared with placebo. [bib_ref] Apalutamide treatment and metastasis-free survival in prostate cancer, Smith [/bib_ref] Similarly in the PROSPER trial in patients with high-risk CRPC, enzalutamide has been shown to be superior to placebo in terms of median metastasisfree survival (36.6 versus 14.7 months, HR 0.29; 95% CI 0.24-0.35), and the key secondary end points of median time to PSA progression (37.2 versus 3.9 months; HR 0.07; 95% CI 0.05-0.08) and time to subsequent antineoplastic therapy (39.6 versus 17.7 months; HR 0.21; 95% CI 0.17-0.26). [bib_ref] Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer, Hussain [/bib_ref] Median overall survival was 67.0 (95% CI 64.0-not reached) months in the enzalutamide group and 56.3 (95% CI 54.4-63.0) months in the placebo group (HR 0.73; 95% CI 0.6-0.89; P 14 0.001). [bib_ref] Enzalutamide and survival in nonmetastatic, castration-resistant prostate cancer, Sternberg [/bib_ref] The phase III ARAMIS trial has shown darolutamide to significantly increase median metastasis-free survival (40.4 versus 18.4 months, HR 0.41; 95% CI 0.34-0.50). [bib_ref] Darolutamide in nonmetastatic, castration-resistant prostate cancer, Fizazi [/bib_ref] Darolutamide also significantly improved overall survival (HR 0.69; 95% CI 0.53-0.88; P 14 0.003) and significantly delayed time to deterioration of prostate cancer-specific quality of life and disease-related symptoms versus placebo. [bib_ref] Nonmetastatic, castrationresistant prostate cancer and survival with darolutamide, Fizazi [/bib_ref] Bicalutamide and low-dose corticosteroids have both shown a benefit in patients with mCRPC in terms of PSA and symptomatic responses. [bib_ref] Prostate specific antigen levels and clinical response to low dose dexamethasone for..., Storlie [/bib_ref] [bib_ref] A randomised phase 2 trial of dexamethasone versus prednisolone in castration-resistant prostate..., Venkitaraman [/bib_ref] Abiraterone plus prednisone has been shown to significantly improve overall survival (HR 0.79; 95% CI 0.66-0.96) in patients with chemotherapynaive asymptomatic/mildly symptomatic mCRPC in the COU-AA-302 trial. [bib_ref] Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with..., Ryan [/bib_ref] In the PREVAIL trial, [bib_ref] Enzalutamide in metastatic prostate cancer before chemotherapy, Beer [/bib_ref] enzalutamide was shown to be superior to placebo in terms of overall survival (HR 0.71; 95% CI 0.60-0.84).
The phase III TAX-327 117 and SWOG-9916 118 trials showed docetaxel (75 ng/m 2 every 21 days) combined with prednisone, and docetaxel (60 mg/m 2 every 21 days) combined with estramustine and prednisone to improve overall survival, compared with mitoxantrone plus prednisone, with HRs of 0.76 (95% CI 0.62-0.94) 117 and 0.80 (95% CI 0.67-0.97), [bib_ref] Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate..., Petrylak [/bib_ref] respectively, while the ALSYMPCA trial showed radium 223 (Ra-223) to significantly increase overall survival (HR 0.70; 95% CI 0.55-0.83) and time to first symptomatic skeletal event (HR 0.66; 95% CI 0.0.53-0.83) in patients with symptomatic, bone-predominant mCRPC. [bib_ref] Alpha emitter radium-223 and survival in metastatic prostate cancer, Parker [/bib_ref] In Japan, a study of Ra-223, in a real-life setting, showed Ra-223 to be well tolerated in all groups. However, the incidences of serious or ! grade 3 treatment-emergent adverse events (TEAEs)/drug-related TEAEs and ! grade 3 haematological TEAEs were numerically higher in the prior-chemotherapy group than in the no prior-chemotherapy group. The safety and effectiveness of Ra-223 in patients without concomitant use of ADT were encouraging, and similar to those in the overall population. [bib_ref] Real-world safety and effectiveness of radium-223 in Japanese patients with castrationresistant prostate..., Uemura [/bib_ref] However, due to the fact that Ra-223 has been associated with an increased incidence of fractures in combination with AAP in the ERA trial, 121 its use in Europe has been restricted to patients who have received at least two lines of systemic therapy for CRPC (abiraterone/ enzalutamide and docetaxel) or who are ineligible to receive these therapies.Administration of Ra-223 in combination with AAP is not permitted. [bib_ref] Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Parker [/bib_ref] For patients who had previously received docetaxel chemotherapy, cabazitaxel improved overall survival (HR 0.70; 95% CI 0.59-0.83) when compared with mitoxantrone in the TROPIC trial, [bib_ref] Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after..., De Bono [/bib_ref] AAP improved overall survival (HR 0.74; 95% CI 0.64-0.86) compared with placebo plus prednisone in the COU-301 trial [bib_ref] Abiraterone and increased survival in metastatic prostate cancer, De Bono [/bib_ref] and enzalutamide improved overall survival (HR 0.63; 95% CI 0.53-0.75) compared with placebo in the AFFIRM trial. [bib_ref] Increased survival with enzalutamide in prostate cancer after chemotherapy, Scher [/bib_ref] However, the optimal sequencing of these agents is still being investigated with evidence to suggest that there may be cross-resistance between the androgen receptor inhibitors abiraterone and enzalutamide. More recently, cabazitaxel has been shown to improve both median radiographic PFS (HR 0.54; 95% CI 0.40-0.73; P < 0.001; 8.0 versus 3.7 months) and median overall survival (HR 0.64; 95% CI 0.46-0.89; P 14 0.008; 13.6 versus 11.0 months) compared with AAP or enzalutamide in patients with mCRPC pre-treated with docetaxel and one of the 'novel' androgen receptor pathway inhibitors, and who progressed within 12 months. [bib_ref] Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer, De Wit [/bib_ref] Also, an international, open-label, phase III trial has been conducted to evaluate 177 Lutetium (Lu)-PSMA-617 (Lu-PSMA) plus standard of care versus standard of care alone in patients who had PSMA-positive mCRPC previously treated with at least one androgen receptor pathway inhibitor and one or two taxane regimens. Standard of care excluded chemotherapy, immunotherapy, Ra-223 and investigational drugs. The addition of Lu-PSMA to standard of care improved both median radiographic PFS (HR 0.40; 99.2% CI 0.29-0.57; P < 0.001; 8.7 versus 3.4 months) and median overall survival (HR 0.62; 95% CI 0.52-0.74; P < 0.001; 15.3 versus 11.3 months) compared with standard of care alone in pre-treated patients with mCRPC. [bib_ref] Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer, Sartor [/bib_ref] All 14 Asian experts accepted completely (100% consensus) the 'recommendations 11a-f' below in the premeeting survey However, based on the publication of the new data on the potential sequencing of agents in the treatment of patients with mCRPC outlined above, [bib_ref] Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer, De Wit [/bib_ref] [bib_ref] Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer, Sartor [/bib_ref] the new recommendation, 'recommendation 11g' below, was discussed and voted on at the virtual meeting and added below and in [fig_ref] Table 1: Summary of Asian recommendations mpMRI should be used to confirm the indication... [/fig_ref] 

## Precision medicinedrecommendations 12a-e
Tissue-based molecular assays may be used in conjunction with all clinico-pathological factors for treatment decision making in patients with localised prostate cancer. Potentially actionable somatic or germline events have been identified in w90% of patients with mCRPC. [bib_ref] Integrative clinical genomics of advanced prostate cancer, Robinson [/bib_ref] The BRCA2 gene is commonly altered and prostate tumours associated with a germline BRCA2 mutation have a high Gleason score, nodal and distant metastases at the time of diagnosis and poor survival. [bib_ref] Germline BRCA mutations are associated with higher risk of nodal involvement, distant..., Castro [/bib_ref] Approximately 20% of metastatic prostate cancers have mutations and alterations involved in DNA damage and repair (DDR) genes 128 with w30% metastatic prostate cancer patients carrying a germline DDR mutation found not to have a previous family history Thus, in Europe, the recommendation is that germline testing for BRCA2 and other DDR gene changes should be offered to all patients with a family history and should be considered for all patients with metastatic prostate cancer. [bib_ref] Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Parker [/bib_ref] There was a lack of consensus amongst the Asian experts with regard to 'recommendation 12a' in the pre-meeting survey However, there was considerable discussion around 'recommendation 13c' with regard to the limited access to MRI especially for asymptomatic patients. Also, the Asian experts considered that there was little point in conducting MRI, if they were not going to use RT in the treatment of asymptomatic patients. Thus, the original 'recommendation 13c' below was revised to cover a more individual approach to the palliative treatment of patients, depending on the individual patient situation, with experts maybe electing to start with a bone-targeting agent or change the existing anticancer treatment depending on the general condition of the patient. Thus, the wording of the initial recommendation was revised to make the use of MRI optional as indicated by the bold text below and 14.
Follow-up and long-term implicationsd recommendations 13a and b The increase in survival times for patients with prostate cancer means that patients spend longer receiving ADT. ADT may cause hot flushes, lethargy, mood swings and significantly osteoporosis. The latter, together with the adverse effects on bone health of abiraterone, enzalutamide, steroids and Ra-223, means that bone health in patients with prostate cancer has become a more important issue. Thus, lifestyle measures to improve bone health are recommended and patients starting long-term ADT should either be offered an oral bisphosphonate or be offered a bone density dual-energy X-ray absorptiometry (DEXA) scan and be treated according to the ESMO guidelines for CTIBL. [bib_ref] Bone health in cancer: ESMO Clinical Practice Guidelines, Coleman [/bib_ref] A management manual exists for CTIBL in Japan. [bib_ref] Management manual for cancer treatment-induced bone loss (CTIBL): position statement of the..., Fukumoto [/bib_ref] There was some discussion about access to and costs of bone-targeting agents and the interpretation of DEXA scans in relation to 'recommendation 14b', but all 14 Asian experts accepted 'recommendations14a and b' without change (i.e. 100% consensus Recently, pembrolizumab monotherapy has shown promising antitumour activity, with an acceptable safety profile, in a small cohort of patients with bone-predominant mCRPC (mostly with MSI disease) previously treated with docetaxel and targeted endocrine therapy, [bib_ref] Pembrolizumab for treatment-refractory metastatic castration-resistant prostate cancer: multicohort, open-label phase II KEYNOTE-199..., Antonarakis [/bib_ref] and has been included in Supplementary [bib_ref] Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Parker [/bib_ref] Following the virtual 'face-to-face' discussions, the revisions were made to the wording of 'recommendations 2b and c, 4f, 6a and 9a' and two new recommendations added, recommendations 11g and 12e [fig_ref] Table 1: Summary of Asian recommendations mpMRI should be used to confirm the indication... [/fig_ref] , and resulted in a 100% consensus in terms of acceptability being achieved for all the recommendations listed in [fig_ref] Table 1: Summary of Asian recommendations mpMRI should be used to confirm the indication... [/fig_ref].
Thus, the recommendations listed in [fig_ref] Table 1: Summary of Asian recommendations mpMRI should be used to confirm the indication... [/fig_ref] can be considered to constitute the consensus clinical practice guidelines for the treatment of patients with prostate cancer in Asia. As mentioned previously, the acceptance of each recommendation by each of the Asian experts was based on the available scientific evidence and was independent of the approval and reimbursement status of certain procedures and drugs in their individual countries. A summary of the availability of the recommended treatment modalities and recommended drugs, as of November 2021, is presented for each participating Asian country in [fig_ref] Table S6 ,: available at https [/fig_ref] , available at https://doi.org/10. 1016/j.esmoop.2022.100518, and will obviously impact some of the disease and patient management strategies that can be adopted by certain countries. vendor Globewerks for their assistance in the execution of the virtual 'face-to-face' meeting of experts. Dr A. Kinsella of Cancer Communications and Consultancy Ltd, Cheshire, UK is acknowledged for her contribution to the preparation of the manuscript. Mrs N. Latino, ESMO Head of Scientific Affairs, is acknowledged for her contribution in the completion of the ESMO-MCBS table.

# Funding
No external funding has been received for the preparation of these guidelines. Production costs have been covered by SSO from central funds.

# Disclosure
RK declares institutional payments from Pfizer, MSD, BMS, Eisai, Amgen, Astellas, J&J, Novartis and Merck and support for meeting attendance or travel from Pfizer, MSD, BMS, Eisai, Amgen, Astellas, J&J, Novartis and Merck. EC declares an institutional grant from Janssen, consulting fees from Astellas, AstraZeneca, Bayer, MSD and Pfizer, fees and honoraria for lectures, presentations from Astellas, Astra-Zeneca, Bayer, Janssen, MSD and Pfizer and support for attending meetings or travel from AstraZeneca and Janssen. AW declares personal fees from MS, MSD, Pfizer, Eisai and IPSEN and participation on a data safety monitoring or advisory board for BMS, MSD, Pfizer, Eisai and IPSEN. KF declares institutional honoraria for participation in advisory boards and talks for: Amgen, Astellas, Astrazeneca, Bayer, Clovis, Janssen, MSD, Novartis/AAA, Pfizer and Sanofi, and personal honoraria for participation to advisory boards for CureVac and Orion. MLKC declares payments or honoraria from ImmunoScape, IQVIA, Telix, Atsellas, AstraZeneca, Bayer, Illumina, Janssen, MSD, Pfizer and Varian, participation on a data safety monitoring or advisory board for AstraZeneca, Astellas, Bayer Pharma, Illumina, Janssen Pharma, MSD Oncology and Varian, a grant from Ferring, stock option in Digital Life Line, a role with the F1000dHead and Neck Cancer Section, Singapore Society of Oncology and Head Neck Caner International Group and other financial interests in Medlever and Varian. HM declares personal fees from CIPLA, Novartis, AstraZeneca, Roche, Eli Lilly, Merck, Pfizer, MSD, CADILA, Bard India and Somex Research. YM declares payments or honoraria from BMS, MSD and Takeda, participation on an advisory board for Chugai Pharmaceutical and Takeda and local PI, institutional, financial interest from MSD. JLL declares institutional grants or contracts from Pfizer, Novartis BMS, Janssen, MSD, Roche/Genetech, AstraZeneca/MedImmune, Seagen Astellas, Bayer, Schering Pharma, Lilly and Merck and participation on a data safety monitoring or advisory board from Pfizer Korea, Astella Korea, BMS, Merck, MSD, AstraZeneca, stocks or stock options from Myovant Sciences, Amgen, Johnson and Johnson and Merck. YSP declares honoraria and consulting fees from MSD, Roche, Merck, Ipsen, BMS/ONO, Novartis, Pfizer, Astellas, Janssen and GSK and support for attending meetings and/or travel from Ipsen, BMS/ONO, Novartis, Pfizer, Astellas and Janssen. MS declares research grants from Johnson and Johnson, payments or honoraria from Johnson and Johnson, AstraZeneca, Amgen and CIPLA, support for meeting attendance from Astellas, fees for participation in data monitoring or advisory boards from Johnson and Johnson, Amgen and AstraZeneca and receipt of equipment/materials for a compassionate programme for drugs/drug samples from Johnson and Johnson, AstraZeneca and Astellas. HJL declares participation on a data safety monitoring or advisory board for Astellas Korea. HK declares payments or honoraria from Astellas, AstraZeneca, Janssen, Sanofi and Takeda and payment for expert testimony and participation in an advisory board for Janssen. KP declares institutional
[fig] Figure 3: High-risk localised and locally advanced prostate cancer treatment algorithm. AAP, abiraterone acetate plus prednisolone/prednisone; ADT, androgen deprivation therapy; EBRT, external beam radiotherapy; HDR, high-dose rate; HIFU, highintensity focused ultrasound; PC, prostate cancer; PSA, prostate-specific antigen; RP, radical prostatectomy; RT, radiotherapy. a For men with biochemical relapse and symptomatic local disease, proven metastases or a PSA doubling time of <3 months. [/fig]
[fig] Figure 4: Metastatic prostate cancer treatment algorithm. AAP, abiraterone acetate plus prednisolone/prednisone; ADT, androgen deprivation therapy, ECOG PS, Eastern Cooperative Oncology Group performance status; PC, prostate cancer; RT, radiotherapy. [/fig]
[table] Table 1: Summary of Asian recommendations mpMRI should be used to confirm the indication for a biopsy in men with elevated PSA, where available [I, A]. 100% 2c. Transperineal ultrasound-guided biopsies are recommended, over transrectal biopsies due to lower infection rates. [III, B]. 100% 2d. Each biopsy should be reported individually and evaluated using the ISUP consensus recommendations [II, B]. 100% Recommendation 3: Staging and risk assessment 3a. Localised disease should be classified as low-, intermediate-or high-risk as a guide to prognosis and therapy [III, A]. 100% 3b. Patients with intermediate-risk disease should be staged for metastases using MRI or CT of the abdomen and pelvis and bone scans [III, B]. Primary ADT alone is not recommended as standard initial treatment for non-metastatic disease [I, D]. 100% 4f. External beam RT plus ADT is recommended for patients with high-risk or locally advanced prostate cancer [I, B]. 100% 4g. External beam RT plus ADT plus AAP (24 months) is recommended for patients with high-risk or locally advanced prostate cancer, as defined by the STAMPEDE trial criteria [I, B]. 100% 4h. RP plus pelvic lymphadenectomy is an option for selected patients with high-risk disease [III, B]. 100% Recommendation 5: Neoadjuvant and adjuvant hormone treatment 5a. Patients receiving radical RT for intermediate-risk disease should be offered a short course of ADT for 4-6 months [I, A]. 100% 5b. Patients receiving radical RT for high-risk disease should have a long course of ADT (18-36 months) [I, A]. 100% 5c. Patients receiving radical RT for high-risk disease who fit the STAMPEDE trial criteria should have a long course of ADT Adjuvant post-operative RT after RP is not routinely recommended. Selected patients with positive surgical margins or extracapsular extension after RP may be offered adjuvant RT [I, B]. Patients having salvage RT to the prostate bed may be offered pelvic nodal RT [I, C]. 100% Recommendation 8: Treatment of relapse after radical treatment 8a. For patients with a local recurrence following RP and no distant metastases, the pros and cons of local salvage therapy should be discussed, taking into account life expectancy and the long natural history of isolated local recurrences [III, C]. ADT alone is recommended as first-line systemic treatment for mHNPC in patients who are unfit for abiraterone, apalutamide, enzalutamide and docetaxel [III, A]. Non-metastatic castrate-resistant prostate cancer 10a. Apalutamide [ESMO-MCBS v1.1 score 3], darolutamide [ESMO-MCBS v1.1 score 3] or enzalutamide [ESMO-MCBS v1.1 score 3] should be considered as options for patients with M0 CRPC and a high risk of disease progression [I, B]. [/table]
[table] Table S6 ,: available at https://doi.org/10. 1016/j.esmoop.2022.100518. The results of the voting by the Asian experts both before and after the 'face-to-face' meeting showed >80% concordance (Supplementary Tables S2 and S3, available at https://doi.org/10.1016/j.esmoop.2022.100518) with the ESMO recommendations for the treatment of patients with prostate cancer. [/table]