Report of the Advanced Prostate Cancer Consensus Conference-JAPAN 2025 at the 112^th Annual Meeting of the Japanese Urological Association

Introduction

With recent progress and advances in drug development, the availability of multiple treatment options for advanced prostate cancer requires clinicians to make careful decisions for each patient. Moreover, advancements in new imaging modalities, biomarkers, radiation technology, and genetic testing have led to many clinical questions and controversies for which high-level evidence is scarce.

The Advanced Prostate Cancer Consensus Conference (APCCC) is a forum for discussing and debating current questions regarding the clinical management of patients with advanced prostate cancer, with a particular focus on these controversies. During the meeting, physicians and scientists who are experts in the field vote and discuss predefined multiple-choice questions about key areas of debate or lack of evidence.

At APCCC 2024, 106 panelists voted for 183 questions on eight different topics, and the voting results and discussions during the meeting served as a practical guide to help physicians and patients make shared decisions about complex controversial areas of clinical management (1). Although two experts in the urological field from Japan attended as panelists during the meeting, half of the panelists were medical oncologists, and 75% of the voting members were from Europe or North America. Considering the differences in medical and health insurance systems between Western countries and Japan, we previously conducted APCCC-JAPAN in 2021 and 2023 during the Annual Meetings of the Japanese Urological Association (2,3) to summarize the real-world status of the management of advanced prostate cancer in Japan, comparing the results of APCCC 2019 and APCCC 2022.

In this study, we summarize and discuss the results of APCCC-JAPAN 2025 and APCCC 2024 to elucidate the current consensus on advanced prostate cancer in Japan. We also evaluated the differences in consensus for similar issues raised in APCCC-JAPAN 2021, 2023, and 2025.

Methods

For APCCC-JAPAN 2025, 16 questions were selected from 183 topics (Table 1) (1) on advanced prostate cancer that have a remarkable effect on daily practice but are supported by insufficient high-level evidence. These topics, which were addressed at APCCC 2024 and considered contextually relevant to the Japanese cohort, were selected through web discussion before the 112^th Annual Meeting of the Japanese Urological Association by a panel of six urologists who are prostate cancer experts, and presented at the meeting.

The panel first presented the questions at APCCC-JAPAN 2025. Japanese urologists attending the symposium voted on the questions on their smartphones using a web-based tool. The urologists were blinded to the APCCC 2024 results for the same questions until on-site voting was completed. The panel then presented the results of APCCC 2024 and the latest evidence on each topic, discussing the voting results of APCCC 2024 and APCCC-JAPAN 2025.

The percentage of each response in the voting results was calculated after excluding the “abstain/unqualified to answer” category. According to the voting results, the maximal participants were 97 urologists (Table 1) (1). In this study, we compared the results of the APCCC 2024 and APCCC 2025-JAPAN and discussed the differences. We also compared the results of similar issues raised in APCCC-JAPAN 2021, APCCC-JAPAN 2023, and APCCC-JAPAN 2025.

Statistical analysis

Fisher’s exact and χ² tests were used, if needed, to evaluate group differences Statistical significance was set at P<0.05 for all analysis; however, P values were not presented since exact statistical issues were not the main subject of this article. All statistical analyses were performed using EZR software (Jichi Medical University, Saitama, Japan).

Results

High-risk localized and locally advanced prostate cancer

• Q3. For high-risk/locally advanced prostate cancer with no metastasis on next-generation imaging, approximately half of the urologists (47%) voted for selecting local radiation plus long-term androgen-deprivation therapy (ADT) alone at APCCC-JAPAN 2025, but significantly fewer voters at APCCC 2024 selected this poll option (10%). At APCCC 2024, 68% of the voters selected radiation plus long-term ADT plus abiraterone for 2 years (Figure 1A).
  

  Figure 1 The results of the APCCC-JAPAN 2025 and the APCCC 2024 voting on the 16 questions are provided. (A-H) The percentage and poll option number are shown in speech bubbles for each question in the pie chart. Each description of poll option of the questions is provided in Table 1. The percentages of each poll option in the voting results were calculated excluding the “abstain/unqualfied to answer” group. APCCC, Advanced Prostate Cancer Consensus Conference.
• Q13. For high-risk/locally advanced prostate cancer with negative prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) results and planned radical prostatectomy (RP), 43% of urologists at APCCC-JAPAN 2025 voted for performing an extended pelvic lymphadenectomy (ePLND) in selected patients. In contrast, 61% of the voters at APCCC 2024 voted for performing an ePLND in the majority of patients (Figure 1A).
• Q26. For patients with pT3b, International Society of Urological Pathology (ISUP) grade group 4–5 disease showing pN1 status following RP with ePLND but with undetectable prostate-specific antigen (PSA) levels and retained continence, most urologists at APCCC-JAPAN 2025 voted for monitoring and early salvage therapy [radiotherapy (RT), systemic therapy, or both] after a confirmed increase in PSA levels. This was similar to the findings of the APCCC 2024 (77% vs. 61%), but the percentage of participants who selected the poll option was lower at APCCC 2024. Moreover, more voters at APCCC 2024 selected adjuvant therapy (39%) than those at APCCC-JAPAN 2025 (23%) (Figure 1B).
• Q34. For patients with persistent PSA levels after RP but pN0 status after ePLND and showing two or more risk factors (R1, pT3, ISUP grade group 4–5), a negative PSMA-PET result postoperatively, and recovering continence, 46% of the voters at APCCC-JAPAN 2025 selected monitoring and salvage therapy after further increase in PSA levels, but only 13% of the voters at APCCC 2024 selected this poll option. At APCCC 2024, most voters selected immediate therapy, and the number of participants selecting immediate therapy differed notably between the two meetings (APCCC 2024: 87% vs. APCCC-JAPAN 2025: 54%) (Figure 1B).

Management of metastatic hormone-sensitive prostate cancer (mHSPC)

• Q67. For patients with high-burden mHSPC who are chemotherapy-fit, 93% and 94% of voters both at APCCC-JAPAN 2025 and APCCC 2024, respectively, selected triplet therapy with ADT plus docetaxel plus androgen receptor pathway inhibitor (ARPI). At APCCC-JAPAN 2023, 90% of the voters selected triplet therapy for synchronous mHSPC (either high volume or independent of disease volume) (2). The number of physicians in favor of triplet therapy for these patients is apparently increasing in Japan, because only 13.5% of the voters chose triplet therapy at APCCC-JAPAN 2021 (3) (Figure 1C).
• Q75. For patients with synchronous low-burden mHSPC on conventional imaging, approximately half of the urologists voted for metastasis-directed therapy (MDT) for all lesions at APCCC-JAPAN 2025; this result was quite different from the APCCC 2024 results (APCCC-JAPAN 2025, 48% vs. APCCC 2024, 17%). In contrast, 40% of the urologists at APCCC-JAPAN 2025 chose MDT for patients based on next-generation imaging findings, which was lower than the percentage of urologists selecting this poll option at APCCC 2024 (57%). However, 12% and 26% of the voters selected no MDT in these cases at APCCC-JAPAN 2025 and APCCC 2024, respectively. At APCCC-JAPAN 2023, a poll option evaluated treatment, including MDT, for patients with low-volume/oligometastatic synchronous mHSPC and 1–3 bone lesions on next-generation imaging, and 46% of the voters chose performing MDT (42% with local RT together with systemic therapy and 4% without systemic therapy), which was similar to the voting percentage at APCCC-JAPAN 2025 (2) (Figure 1C).
• Q89. For patients with mHSPC showing deep remission after systemic therapy (e.g., PSA <0.2 ng/mL) and no relevant adverse reactions, approximately half of the urologists (48%) voted for continuation of systemic therapy at APCCC-JAPAN 2025, and the result was higher than that at APCCC 2024 (26%). In contrast, 52% and 74% of the voters at APCCC-JAPAN 2025 and APCCC 2024, respectively, considered discontinuation of systemic therapy, whether early or late during therapy (Figure 1D).
• Q96. Among patients with high-volume synchronous mHSPC without relevant local symptoms, 67% of physicians at APCCC 2024 voted against recommending local radiation, whereas in APCCC-JAPAN 2025, 64% of urologists voted for recommending local radiation in the majority (13%) or only selected (51%) cases. The differences were statistically significant (Figure 1D).

Management of metastatic castration-resistant prostate cancer (mCRPC)

• Q108. Without somatic genetic testing, the urologists at APCCC-JAPAN 2025 favored docetaxel in patients with first-line mCRPC after receiving ADT plus ARPI (81%). This tendency was also observed at APCCC 2024 (85%), and a consensus was reached for docetaxel as first-line treatment after ADT plus ARPI for patients with mCRPC. Docetaxel was again selected as the most common treatment in APCCC-JAPAN 2023, but 31% of the voters at APCCC-JAPAN 2023 selected Rad 223, which was quite different from the results at APCCC-JAPAN 2025, where only 8% of the voters at APCCC-JAPAN 2025 chose Rad 223 as a sequential treatment (2) (Figure 1E).
• Q133. For patients with oligoprogressive mCRPC, 72% of the urologists at APCCC-JAPAN 2025 voted for switching systemic therapy, either with MDT for all progressing lesions or not, which was higher than the results at APCCC 2024 (51%). In contrast, at APCCC 2024, 49% of the voters chose not to change systemic therapy and perform MDT for all progressive lesions, which was higher than the results at APCCC-JAPAN 2025 (28%). The same poll option was presented at APCCC-JAPAN 2023, and similarly, 74% voted for switching systemic therapy either with or without MDT for all progressing lesions; however, the percentage of voters who chose the option of simply changing systemic therapy without MDT was higher at APCCC-JAPAN 2025 (APCCC-JAPAN 2023, 21% vs. APCCC-JAPAN 2025, 42%) (2) (Figure 1E).

Bone protection in advanced prostate cancer

• Q177. A combined total of 78% and 98% of the participants voted in favor of antiresorptive therapy, at least in selected patients, at APCCC-JAPAN 2025 and APCCC 2024, respectively. However, 22% of the urologists selected “No” for antiresorptive therapy for mHSPC patients with long-term ADT at APCCC-JAPAN 2025. This was significantly different from the results of APCCC 2024, where only 2% selected “No” for the question (Figure 1F).
• Q183. Although a combined total of 92% of participants were in favor of stopping or reducing the administration frequency of bone-targeting agents for mCRPC patients after 2 years at APCCC 2024, 65% of the urologists at APCCC-JAPAN 2025 voted for stopping or reducing the agents, which was significantly lower than that at APCCC 2024. At APCCC-JAPAN 2025, 35% of the urologists chose administrating the agents monthly, even after 2 years (Figure 1F).

Genetics

• Q101. For patients with mHSPC, 58% of the urologists at APCCC-JAPAN 2025 did not think that the information from genetic evaluation would influence the decision on first-line treatment in the majority of the patients, but the percentage of voters who selected this poll option was lower than that at APCCC 2024 (APCCC-JAPAN 2025, 58% vs. APCCC 2024, 76%) (Figure 1G).
• Q102. For patients with mCRPC, 83% and 80% of the voters at APCCC-JAPAN 2025 and APCCC 2024, respectively, thought that the information from genetic evaluation would influence the decision regarding first-line treatment in the majority of the patients, which was remarkably different from Q101 (Figure 1G).
• Q103. For patients with mCRPC, 92% and 95% of the voters at APCCC-JAPAN 2025 and APCCC 2024, respectively, were in favor of genetic testing. However, at APCCC-JAPAN 2025, 30% of the urologists voted for germline testing depending on the situation, whereas none of the voters at APCCC 2024 selected this poll option (Figure 1H).
• Q122. For patients with mCRPC with inactivating CDK12 alterations, 75% of the voters at APCCC-JAPAN 2025 chose to recommend treatment with a polyadenosine diphosphate ribose polymerase (PARP) inhibitor, and the percentage was slightly higher than that at APCCC 2024 (65%). Approximately 40% of the voters at both APCCC-JAPAN 2025 and APCCC 2024 chose the poll option recommending PARP inhibitors at a later stage of the disease in comparison with patients with BRCA2 alterations (Figure 1H).

Discussion

Treatment of high-risk localized and locally advanced prostate cancer

For patients showing high-risk localized and locally advanced prostate cancer on conventional imaging, the National Comprehensive Cancer Network (NCCN) recommends RT (74 Gy in 37 fractions) to the prostate in combination with long-term ADT (at least 2 years) with or without abiraterone; for very high-risk patients, including those with node-positive disease (cN1 M0) according to the STAMPEDE criteria (defined as ≥2 of the following characteristics: ≥ cT3, ISUP grade group ≥4, and PSA ≥40 ng/mL), addition of abiraterone to the combination therapy is preferred, depending on the results from the STAMPEDE trial (4,5). Approximately half of the Japanese urologists at APCCC-JAPAN 2025 chose RT plus ADT alone for the disease, since abiraterone for patients with non-metastatic high-risk localized prostate cancer is not covered by Japanese medical insurance (Q3). However, 18% of the voters selected RT plus ADT plus 2-year abiraterone based on STAMPEDE trial (4), assuming that all treatments were available. Thus, 65% of the urologists voted for RT plus long-term ADT ± abiraterone, which was slightly lower than the APCCC 2024 results. Interestingly, 27% and 22% of the voters at APCCC-JAPAN 2025 and APCCC 2024, respectively, almost the same percentage of the voters, voted for RP as a part of multimodal therapy, even if the background of the voters was quite different between the meetings; the majority of the former voters were urologists, but urologists only constituting 27% of the latter panel. As reflected in the results of APCCC-JAPAN 2025, in the latest Japanese clinical practice guidelines for prostate cancer, there is no recommendation as to whether surgery or radiation plus ADT is better, and the guidelines state that the patient’s condition, circumstance, and desires should be considered (6).

ePLND is preferred when pelvic lymphadenectomy (PLND) is performed for intermediate- or high-risk patients because removing more lymph nodes is associated with an increased chance of detecting lymph-node metastases, providing more accurate staging and prognostic information (7,8). No definitive evidence indicating a therapeutic benefit of PLND has been reported (9); however, an update on a single-center randomized clinical trial comparing the therapeutic outcomes of limited versus extended PLND for localized prostate cancer showed that ePLND reduced the incidence of metastasis, but not of biochemical recurrence (BCR), compared to a limited PLND template in patients who received RP (10,11). Therefore, the most recent NCCN guideline (Version 2, 2025) has adopted this evidence and has changed its description, showing that PLND may cure some patients with microscopic metastases (NCCN guideline). PSMA-PET plays a pivotal role in the diagnosis and staging of prostate cancer (12). When considering pathological findings as the reference, PSMA-PET demonstrated very high specificity, making it a valuable diagnostic tool for ruling out lymph-node involvement when combined with other clinical information. However, the relatively low sensitivity of this technique suggests that it may miss positive cases, particularly those involving micrometastatic disease. Therefore, the decision to perform ePLND in high-risk patients with higher positive lymph-node involvement rates should not be determined only by PSMA-PET results, but should be considered with additional patient data [such as Gleason grade and local stage evaluated by magnetic resonance imaging (MRI)] (12-14).

At APCCC-JAPAN 2025 and APCCC 2024, 62% and 71% of the voters, respectively, selected performing ePLND for the majority of patients or selected high-risk localized prostate cancer patients with negative PSMA-PET results. In the Japanese guidelines, lymph node dissection is not necessary for low-risk cases, but extended lymph node dissection is weakly recommended for intermediate- and high-risk cases (6). However, at APCCC 2024, 61% chose ePLND for the majority of patients, while at APCCC-JAPAN 2025, only 19% chose it. These results reflect differences in perceptions regarding the usability of PSMA-PET in daily clinical practice and whether physicians are aware of the characteristics of this imaging examination.

Patients with prostate cancer showing pN1 status after RP and PLND have a worse prognosis than those with node-negative disease; however, the long-term prognosis of this cohort is highly heterogeneous and varies substantially according to disease characteristics (15,16). Retrospective analysis revealed that up to one out of four patients managed with initial observation would not experience BCR at the 5-year follow-up, and the 5-year cancer-specific survival (CSS) and overall survival (OS) rates exceeded 90% for selected node-positive patients with favorable characteristics, including undetectable postoperative PSA, less than three positive nodes, lymph-node metastasis with diameter ≤2 mm, negative margins, and nonaggressive histology (Gleason score of <8 and no pT3b/pT4) (15,17,18). In contrast, patients with higher-risk characteristics, including PSA persistence, three or more positive nodes, maximum tumor diameter >2 mm, positive margins, and aggressive histological findings, may benefit from adjuvant therapy, such as ADT and/or postoperative RT (15,17,18). Without high-level evidence for the management of pN1 at RP, management should be tailored in accordance with the disease severity.

Patients with PSA persistence after RP have worse outcomes, even if they are node-negative (19-21). Patients with high-risk factors, such as high D’Amico risk, Gleason score ≥8, pT stage ≥3, positive surgical margins, presence of intraductal carcinoma of the prostate, and lymph-node involvement, were more likely to present with PSA persistence (20,22). Since the introduction of PSMA-PET/computed tomography (CT), the detection rate of metastases has substantially improved in comparison with that of conventional imaging modalities, especially in patients with biochemical relapse (23). However, among patients with PSA persistence after RP, PSMA-PET/CT positivity was observed in 42% of patients with PSA values less than 0.5 ng/mL and 68% of patients with PSA values from 0.5 to less than 1.0 ng/mL; therefore, prostate cancer lesions could not be detected in a substantial proportion of patients (24). Patients with persistent PSA levels after RP may benefit from immediate RT with or without ADT; however, the current evidence is limited (25). The differences in strategy between the two meetings may depend on the prevalence and experience with PSMA-PET/CT in daily practice or whether any description with regards to pN1 or PSA persistence in each regional guideline can be seen. Actually, in the Japanese guideline, no recommendation or clinical question is available both for pN1 or PSA persistence disease after RP (6).

Management of mHSPC

Triplet systemic therapy consisting of ADT plus six cycles of docetaxel plus abiraterone or darolutamide (PEACE 1 and ARASENS trials) improved OS compared with doublet therapy consisting of ADT plus six cycles of docetaxel (26,27). Subgroup analysis revealed that patients with high volume consistently showed a benefit in terms of OS when they received systemic triplet therapy compared with ADT plus docetaxel (28). At APCCC-JAPAN 2025 and APCCC 2024, more than 90% of voters were in favor of recommending triplet therapy, either for the majority or at least for selected patients. Based on the results of APCCC-JAPAN 2021, 2023, and 2025, triplet therapy for high-volume synchronous mHSPC is becoming widespread in Japan (2,3).

To date, the advantages of MDT for metachronous mHSPC have been reported in prospective studies, but robust evidence of MDT for synchronous mHSPC is hardly found (29-32). Further prospective and retrospective analyses combined with data from new-generation imaging modalities such as PSMA-PET/CT are required; in the Japanese guideline, no recommendation or clinical question is yet available for the issue (6). Although the majority of physicians attending APCCC 2024 or APCCC-JAPAN 2025 chose additional MDT for synchronous low-burden mHSPC, the difference in the cost of radiation therapy may be related to determining whether to apply MDT to those patients, owing to the lack of strong evidence in favor of using MDT in these patients.

The introduction of ADT plus ARPI or ADT plus ARPI plus docetaxel has prolonged the survival of patients with mHSPC. Among patients who received double or triple therapies, those who demonstrated a robust PSA decline showed favorable outcomes, including long-term survival (33,34). In contrast, the addition of ARPI to traditional ADT is associated with an increased risk of cardiovascular events (35,36). Patients with mHSPC who initiate treatment with ARPI earlier are exposed to intensive androgen suppression for a longer duration; therefore, a 2-fold increase in cardiovascular morbidity was associated with the addition of an ARPI, and up to a 4-fold risk was associated with the combined use of two ARPIs (35). Considering these issues, mHSPC patients who achieved deep PSA response (PSA ≤0.2 ng/mL or 90% PSA decline ≥90%) on systemic therapy may be candidates for switching to intermittent therapy or de-escalating (complete interruption of systemic therapy or stopping ARPI only) treatment (37,38). The OS of patients with mHSPC in the USA was quite different from that of patients in Japan (39,40), revealing that the OS of Japanese patients with mHSPC was much better than that of patients in the USA (41). Because of this issue, before voting, voters of APCCC-JAPAN 2025 would be more predisposed to selecting interruption of systemic therapy than voters of APCCC 2024; however, the results were the opposite. Thus, the physicians in APCCC 2024 may have placed more importance on the adverse events associated with hormone therapy.

Two phase 3 trials have evaluated the effect of prostate RT on outcomes in patients with de novo mHSPC (42-44). Although these trials did not reveal the benefits of prostate RT for OS in patients with mHSPC, the STAMPEDE trial showed an improvement in OS in a subgroup of patients with low-volume metastatic disease (43). The PEACE-1 trial showed that prostate RT for de novo mHSPC improved radiographic progression-free survival (rPFS) and delayed the onset of serious genitourinary adverse events and occurrence of castration-resistant prostate cancer (CRPC), regardless of the metastatic burden (45). The majority of the physicians attending APCCC 2024 and APCCC-JAPAN 2025 did not consider that prostate RT for all patients with high-burden mHSPC was appropriate. We should wait for the results of an ongoing randomized controlled phase III trial to confirm the superiority of local RT in addition to anti-androgen therapy for high-volume patients with mHSPC [the Japan Clinical Oncology Group (JCOG) 2011: HimeRT study].

Treatment for mCRPC

Currently, no definitive treatment recommendations are available for mCRPC that progresses after treatment with ADT plus ARPI or ADT plus ARPI plus docetaxel for mHSPC. Extrapolating from previous evidence, sequencing of ARPIs such as enzalutamide to abiraterone or abiraterone to enzalutamide is not recommended because of cross-resistance, especially when the time of response to ADT plus ARPI for mHSPC is short and the disease shows high grade with rapid progression (46,47). Therefore, docetaxel selected as an option at APCCC 2024 and APCCC-JAPAN 2025, Rad 223 with or without enzalutamide, cabazitaxel, or a PARP inhibitor plus ARPI, in some situations, are options for patients with mCRPC who have already received ARPIs and are not available for genetic testing (48-53). However, in the Japanese guideline, no recommendation is available since there is no clear evidence of superiority among unused ARPI, docetaxel and others as the first-line treatment for mCRPC after upfront therapy for mHSPC (6). In real-world analyses, patients with non-negligible mCRPC received attempted treatment with at least one additional ARPI despite prior treatment with ARPIs (54-56). This may be due to patient preference, concerns over adverse reactions, worsening quality of life with chemotherapy, advanced age, frailty, and multiple comorbidities, which prevent the selection of docetaxel or cabazitaxel (57).

The concept of treating oligoprogressive mCRPC with MDT focuses on eliminating resistant clones of cancer to continue the current line of systemic therapy or to control the disease more efficiently with the next line of systemic treatment. However, evidence for the effectiveness of MDT in oligoprogressive sites of mCRPC is limited.

Two prospective studies suggested that MDT against progressive sites in patients with mCRPC receiving ongoing hormonal therapy may delay the need to start a new line of systemic therapy without severe toxicity (58,59). In the European Society for Radiotherapy and Oncology Delphi consensus, radiation oncologist experts recommended MDT for all lesions of progressive disease detected using PSMA-PET without switching to systemic therapy based on a patient-friendly concept, thereby avoiding the adverse events associated with subsequent treatments (59). In contrast, at APCCC-JAPAN 2025, a significant number of voters selected systemic therapy without MDT for patients with oligoprogressive mCRPC. This result may be influenced by the growing number of options for mCRPC treatment or the characteristics of the meeting attendees; however, the actual reason remains unclear.

Bone health in prostate cancer

Despite the benefits associated with ADT plus ARAI and/or chemotherapy, long-term treatment with these drugs causes several adverse reactions, including deterioration of bone health, such as an increased risk of bone fracture and falls, which are associated with morbidity and mortality (60,61). Similar to the panelists at APCCC 2024, the voters at APCCC-JAPAN 2025 seemed to be aware of treatment-induced bone loss; thus, most voters selected the addition of BPAs, at least in selected patients. However, the percentage of respondents who selected this response was higher in APCCC 2024. In contrast to the European Society for Medical Oncology (ESMO) or NCCN guidelines or the STAMPEDE trial (5,60,61), the administration of bone-protecting agents (BPAs) to patients with mHSPC is not recommended in the Japanese guideline; therefore, the percentage of voters at APCCC-JAPAN 2025 selecting the preference for adding BPAs to systemic therapy may be lower than that at APCCC 2024 (6).

Medication-related osteonecrosis of the jaw (MRONJ) in mCRPC patients with prolonged administration of denosumab or zoledronic acid is an important adverse event that cannot be ignored; the incidence of MRONJ in patients receiving treatment is approximately 1% per year (60,62). In a retrospective study focusing on Japanese patients with urological malignancies who received BPAs, among 168 prostate cancer patients, 22% were diagnosed with MRONJ during the follow-up period (mean, 585 days) (63), and dental extraction is a risk factor for MRONJ (63,64). According to the REaCT study, which included patients with breast and prostate cancer, de-escalating BPA treatment is feasible in terms of reduction of symptomatic skeletal event rates and cost-effectiveness; however, the optimal timing and de-escalation dosage remain unknown (65). At APCCC 2024, the vast majority of panelists voted in favor of either stopping BPAs after 2 years or reducing their administration; however, at APCCC-JAPAN 2025, 35% of the voters selected continuation of BPAs after 2 years of administration. The decision was probably influenced by the voters’ clinical backgrounds and experiences; however, the reason remains unclear.

Genetic analysis for clinical practice

The European Association of Urology (EAU) guidelines recommend somatic genomic testing for patients with mCRPC, preferably before first-line mCRPC treatment (66) (Tables 2,3). However, the NCCN guidelines recommend germline and somatic genetic testing for patients with mHSPC, which is earlier than the former guidelines (5) (Tables 2,3). The Japanese Urological Association has provided recommendations for the optimal use of genetic testing to determine the suitability of PARP inhibitors for prostate cancer. Genetic testing is recommended for patients with mCRPC, especially before first-line treatment, according to the EAU guidelines (Tables 2,3).

At the time of APCCC 2024 and APCCC-JAPAN 2025, no definitive evidence was available to explain how genetic testing could influence the management of mHPSC patients; however, the results of the AMPLITUDE phase 3 trial were reported at the America Society of Clinical Oncology 2025 (67). In this trial, patients with mHSPC harboring at least one homologous recombination repair (HRR) alteration in one of the following genes were randomized 1:1 to receive either niraparib + abiraterone + ADT or placebo + abiraterone + ADT: BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, PALB2, RAD51B, and RAD54L (67). The primary endpoint (PE) was rPFS. The AMPLITUDE trial met its PE, demonstrating that the combination of niraparib + abiraterone + ADT significantly reduced the risk of rPFS or death by 48% in the BRCA alteration group and 37% in the broader HRR alteration group (67). Interestingly, among voters at APCCC-JAPAN 2025, 42% thought that information from genetic evaluations should influence the decision for first-line treatment of mHSPC; this percentage was higher than that at APCCC-2024. Theoretically, if patients with mHSPC possess either somatic or germline BRCA1/2 alterations, PARP inhibitors would be the most potent therapeutic drugs; therefore, genetic results may alter the decision regarding the therapeutic approach. The difference might be due to the backgrounds of the voters, since at APCCC-JAPAN 2025, most voters were urologists, but approximately 3/4 of the panelists at APCCC 2024 were medical oncologists or clinical/radiation oncologists (68). We are awaiting the final results of other trials in the mHSPC setting (NCT04821611, TALAPRO-3, NCT06120491, and EvoPAR-PR01). In contrast, information from genetic evaluation of mCRPC was found to influence treatment-related decision-making for first-line treatment of the patients in more than 80% of the voters at APCCC 2024 and APCCC-JAPAN 2025; this can be attributed to strong evidence showing that patients with either somatic or germline BRCA1/2 alterations would benefit from receiving a PARP inhibitor with or without an ARPI, according to known phase 3 trials (52,53,69-71).

Another aspect without consensus was the use of somatic or genetic evaluations, or both, for genetic testing of patients with prostate cancer at APCCC-JAPAN 2025, similar to APCCC 2024. In Japan, BRACAnalysis, which can identify only BRCA1/2 germline variants, is available as a companion diagnostic tool for patients receiving olaparib. This genetic testing tool presents a lower hurdle than comprehensive genomic analysis because facilities are allowed to perform testing as long as a system for genetic counseling is available (6). Therefore, at APCCC-JAPAN 2025, 30% of the voters selected germline testing only as a routine genetic evaluation for patients with mCRPC, whereas none voted for the same answer at APCCC 2024. However, BRACAnalysis alone may miss somatic variants of BRCA1/2 commonly observed in prostate cancer (72). In contrast, using FoundationOne CDx with tumor tissue samples or FoundationOne Liquid CDx to assess circulating tumor DNA in the blood can identify somatic alterations, and the results may lead to confirmatory germline testing. Thus, performing somatic testing plus or minus germline testing only in cases of relevant somatic alterations, or performing somatic and germline testing from the beginning for a comprehensive evaluation, would be the ideal method (5,73,74). However, for genomic diagnosis through somatic genetic testing, patients must undergo an expert panel judgment of the test results at a core or base hospital in Japan. In addition to posing a major financial burden, the complexity of the procedures is a hurdle in such cases.

Mutations in CDK12 are found in approximately 10–23.3% of Japanese patients with mCRPC, and these patients show aggressive clinical features (75-80). Clinical data indicate a poor prognosis with minimal benefit from PARP inhibitor monotherapy in patients with prostate cancer and CDK12 alterations (81). However, a recent live interactive systematic review and meta-analysis showed a statistically significant improvement in rPFS in patients with CDK12 alterations who received PARP inhibitor plus ARPI therapy (82). The HRR pathway may not be equivalent in eliciting a response to PARP inhibitor therapy. A gene-specific approach appears to be optimal for guiding the appropriate use of PARP inhibitors in mCRPC; however, these issues should be addressed in the future.

Conclusions

We summarized the voting results for 16 clinical questions on advanced prostate cancer management at APCCC-JAPAN 2025. For the same questions at APCCC 2024, we identified both similarities and differences in the management approaches of Japanese urologists and prostate cancer specialists.

Acknowledgments

We would like to thank the JUA members for attending JUA 2025. We would also like to thank Editage (www.editage.jp) for editing the English language.

Footnote

Data Sharing Statement: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-709/dss

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-709/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-709/coif). T.I. received honoraria for lectures from Astellas Pharma, AstraZeneca, Bayer, Tsumura, and Janssen. T.K. received honoraria for lectures from Astellas Pharma, Pfizer, and Janssen. M.K. received research funding from AstraZeneca. A.Y. received honoraria for lectures from Astellas Parma, AstraZeneca, Bayer, and Janssen. M.E. reports honoraria for lectures from Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Janssen, Merck Biopharma, Novartis, MSD, Ono Pharmaceutical, Pfizer, and Takeda Pharmaceutical, and research funding from MSD. I.H. reports personal honoraria from Astellas Pharma, Bayer, Takeda, and Bayer. H.S. reports receiving honoraria for lectures from Astellas Pharma, AstraZeneca, Bayer, Ferring Pharmaceuticals, Janssen, and Sanofi, and funding from Astellas Pharma, AstraZeneca, Bayer, Eli Lilly, MSD, and Janssen, and consulting fees from Bayer, Ferring Pharmaceuticals, Janssen, Nihon Mediphysics, and Novasrtis. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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