Changes in the trends of initial treatment for newly diagnosed prostate cancer in Japan: a nationwide multi-institutional study.

BACKGROUND: In previous large-scale studies conducted through 2010, androgen deprivation therapy (ADT) was the most common initial treatment for prostate cancer patients in Japan. However, recent advancements in treatment technologies have significantly affected the management of prostate cancer in Japan. This study analyzed the trends in initial treatments for prostate cancer based on two nationwide surveys. METHODS: Two Japan-wide multi-institutional surveys, J-CaP2010 and J-CaP2016, were conducted to enroll patients newly histologically diagnosed with prostate cancer in 2010 and 2016-18, respectively. Both surveys included age at diagnosis, initial PSA level, ISUP Grade Group, TNM classification, and initial treatment for prostate cancer. RESULTS: J-CaP2010 included data from 8192 patients across 140 institutions, whereas J-CaP2016 included data from 21 841 patients across 186 institutions. In J-CaP2016, the proportion of radical prostatectomy (RP) and radiation therapy (RT) in the initial treatment increased (from 32% to 36% and 21% to 26%, respectively), whereas the proportion of ADT decreased (from 40% to 29%) compared with those in J-CaP2010. The increase in RP or RT was noticeable in patients aged 75 years and older (from 20% to 38%) and those with high-risk localized cancer (from 58% to 74%) or locally advanced cancer (from 38% to 56%). The proportion of active surveillance or watchful waiting increased in patients with low-risk localized cancer (from 21% to 41%). The proportion of robot-assisted RP within all RPs and the proportion of intensity-modulated RT within all RTs increased remarkably (from 2.3% to 78% and 20% to 50%, respectively). CONCLUSIONS: In Japan, RP and RT have increased as initial treatments for prostate cancer, whereas ADT has decreased. Consequently, RP has emerged as the most commonly selected initial treatment, replacing ADT.

A multicenter, retrospective observational study investigating baseline characteristics and clinical outcomes in patients with hormone-sensitive prostate cancer treated with primary androgen deprivation therapy.

OBJECTIVE: This multicenter, retrospective, observational study investigated baseline characteristics and clinical outcomes in patients with hormone-sensitive prostate cancer who received primary androgen deprivation therapy, using Japan Study Group of Prostate Cancer registry data. METHODS: Among patients in the Japan Study Group of Prostate Cancer registry, those who initiated primary androgen deprivation therapy and were aged 20 years or older were enrolled in this study. The primary endpoint was time to disease progression, defined as time from primary androgen deprivation therapy initiation to either prostate-specific antigen or clinical progression. Secondary endpoints included prostate-specific antigen progression-free survival, prostate-specific antigen response (90% or greater reduction from baseline) and distribution of second-line treatment. RESULTS: Of the 2494 patients (goserelin, n = 564; leuprorelin, n = 1148; surgical castration, n = 161; degarelix, n = 621), those who received degarelix had higher prostate-specific antigen levels and Gleason scores and were at a more advanced clinical stage than those receiving goserelin or leuprorelin. The median time to disease progression (identical to the prostate-specific antigen progression-free survival result) was not reached for goserelin and leuprorelin, 52.7 months for surgical castration and 54.0 months for degarelix. Although baseline prostate-specific antigen values in the degarelix cohort were higher than those of the leuprorelin or goserelin cohorts, prostate-specific antigen responses were not different among the three cohorts. Regarding second-line treatment, the largest patient group received degarelix followed by leuprorelin (n = 195). CONCLUSIONS: This study clarified patient characteristics and long-term effectiveness of primary androgen deprivation therapy in real-world clinical practice. Japanese urologists appear to select appropriate primary androgen deprivation therapy based on patient background and tumour characteristics, with degarelix largely reserved for higher risk patients.

Improved survival of poor-risk non-seminomatous germ cell tumor patients: real-world data from a single institute in Japan.

OBJECTIVES: The International Germ Cell Cancer Collaborative Group Update Consortium showed the improved survival of patients with a non-seminomatous germ cell tumor. We updated the survival data of the non-seminomatous germ cell tumor patients treated at our hospital. PATIENTS AND METHODS: We analyzed the outcomes of 138 patients treated in 1981-2018. We compared the survival of the patients treated in the early (1981-99) and later (2000-18) periods and determined the groups' progression-free survival and overall survival using the Kaplan-Meier method. We used a web-based application of the International Germ Cell Cancer Collaborative Group Update model to calculate each patient's predicted 3-year progression-free survival. RESULTS: The 5-year progression-free survival rates of the good, intermediate and poor prognosis groups were 91, 83 and 64%, and their 5-year overall survival rates were 97, 89 and 82%, respectively. There were no significant differences in the progression-free survival or overall survival of the good and intermediate prognosis groups by treatment year. The 5-year progression-free survival of the poor prognosis group was almost identical in both treatment year (60 and 65%, respectively). By contrast, the 5-year overall survival in the later period (85%) was higher than that in the early period (70%). The median-predicted 3-year progression-free survival rates of the good, intermediate and poor prognosis groups were 92, 83 and 51% (P < 0.01), respectively. The concordance index for the good, intermediate and poor prognosis groups were 0.56, 0.79 and 0.67, respectively. CONCLUSION: The survival of our poor prognosis non-seminomatous germ cell tumor patients improved over time. The 5-year overall survival of patients treated in 2000-18 reached 85%.

[A Case of Germ Cell Tumor in which Necrotic Tissue Revealed hCG-Positive in Surgical Specimen of Post-Chemotherapy Retroperitoneal Lymph Node Dissection].

The patient was a 27-year-old male. In December 2020, he was diagnosed with a primary extragonadal germ cell tumor of the retroperitoneum with inferior vena caval (IVC) involvement. After 3 courses of bleomycin, etoposide and cisplatinum and 3 courses of paclitaxel, ifosfamide and cisplatin, the serum human chorionic gonadotropin (hCG) level remained abnormally low. He was referred to our department after follow-up for 2 months. Since the hCG level continued to decrease during follow-up, we decided to perform marker-positive surgery. He underwent retroperitoneal lymph node dissection. We also resected a part of the IVC wall and tumor in the IVC. The serum hCG level was normalized at 5 days after surgery. Pathological examination revealed only necrotic tissue. Immunohistochemistry showed hCG positive in the necrotic tissue.

Efficacy of combined androgen blockade therapy in patients with metastatic hormone-sensitive prostate cancer stratified by tumor burden.

OBJECTIVE: To determine the effect of combined androgen blockade with a first-generation anti-androgen on the prognoses of metastatic hormone-sensitive prostate cancer patients stratified by tumor burden. METHODS: We retrospectively analyzed the cases of metastatic hormone-sensitive prostate cancer patients who were treated with androgen deprivation therapy in 2008-2017 at 30 institutions in Japan. To compare the overall survival and progression-free survival rates of the patients treated with castration monotherapy and combined androgen blockade, we carried out a Cox proportional hazards regression analysis using both inverse probability of treatment weighting and instrumental variables methods. High-burden disease was defined as the presence of four or more bone metastases and/or visceral metastasis. RESULTS: Of 2048 patients, 702 (34.3%) and 1346 (65.7%) patients were classified as the low- and high-burden groups, respectively. In each group, >80% of the patients were treated with combined androgen blockade. Although there was no significant between-group difference in the overall survival according to the androgen deprivation therapy method, in the high-burden group the progression-free survival of the combined androgen blockade-treated patients was significantly better than that of patients treated with castration monotherapy: inverse probability of treatment weighting method, hazard ratio 0.49, 95% confidence interval 0.34-0.71; instrumental variables method, hazard ratio 0.80, 95% confidence interval 0.60-0.98. CONCLUSION: In the high-burden group, combined androgen blockade with a first-generation anti-androgen resulted in superior progression-free survival compared with castration monotherapy. For well-selected metastatic hormone-sensitive prostate cancer patients, the use of combined androgen blockade might still have some suitable scenarios.

Recent trend of androgen deprivation therapy in newly diagnosed prostate cancer patients: Comparing between high- and middle-income Asian countries.

The number of newly diagnosed prostate cancer cases varies across Asia, with higher mortality-to-incidence ratio reported in developing nations. Androgen deprivation therapy (ADT), alone or in combination, remains the mainstay of first-line treatment for advanced prostate cancer. Key findings of extensive research and randomized controlled trials have shaped current clinical practice and influenced clinical guideline recommendations. We describe here the recent trend of ADT in newly diagnosed prostate cancer for Asia focusing on Japan (high-income country) and Malaysia (middle-income country) based on the Asian Prostate Cancer (A-CaP) Study. The combination of radiotherapy and ADT or ADT alone was common in patients with intermediate-to-high risk localized and locally advanced disease. For metastatic prostate cancer, maximum androgen blockade (gonadotrophin-releasing hormone [GnRH] agonist/antagonist plus antiandrogen) was prevalent among the Japanese patients while primary ADT alone with GnRH agonist/antagonist was widely practiced in the Malaysian cohort. Upfront combined therapy (ADT plus docetaxel or androgen receptor pathway inhibitor) has significantly improved the outcomes of patients with metastatic castration-naïve prostate cancer. Its application, however, remains low in our cohorts due to patients' financial capacity and national health insurance coverage. Early detection remains the cornerstone in prostate cancer control to improve treatment outcome and patient survival.

Long-term outcomes of androgen deprivation therapy in prostate cancer among Japanese men over 80 years old.

This study aimed to analyze the survival rate and to examine the risk of death from prostate cancer when accounting for competing risk of death, in men aged ≥80 y treated with primary androgen deprivation therapy (ADT). Data of patients with prostate cancer who had received ADT were extracted from a nationwide community-based database established by the Japan Study Group for Prostate Cancer. Prognostic variables, including progression-free survival, cancer-specific survival, overall survival, and death rates were compared between men stratified by prostate cancer risk. Overall, 4760 patients older than 80 y were included. The proportion of low-, intermediate-, high-, or very high-risk, regional, and metastatic prostate cancer among super-elderly men was 9.5%, 14.6%, 48.8%, 9.0%, 3.2%, and 24.9%, respectively. Survival rates decreased with increasing risk stratification. The cumulative 5-y death rate by prostate cancer for low-, intermediate-, high-, or very high-risk, regional, and metastatic prostate cancer, was 0.92% (95% confidence interval [CI]: 0.2%-3.6%), 1.6% (95% CI: 0.8%-3.4%), 5.75% (95% CI: 4.25%-7.75%), 15.6% (95% CI: 11.6%-23.3%), 20.7% (95% CI: 13.1%-31.7%), and 36.9% (95% CI: 32.8%-41.4%), respectively. Our findings support that there is no need for immediate ADT for low- and intermediate-risk groups. Conversely, in high- or very high-risk, regional, and metastatic prostate cancer, more efforts for curative therapy and intensive therapy are needed in selected patients.

Regional and facility disparities in androgen deprivation therapy for prostate cancer from a multi-institutional Japan-wide database.

OBJECTIVES: To examine the differences in prognosis of prostate cancer patients receiving primary androgen deprivation therapy by region and facility type using a Japan-wide database. METHODS: Data on patients treated with primary androgen deprivation therapy between 2001 and 2003 from a nationwide community-based database established by the Japan Study Group of Prostate Cancer were obtained. Clinicopathological characteristics and prognostic variables, including progression, cancer-specific survival and overall survival, were compared according to region and facility type where the patients were treated. RESULTS: Among 19 162 patients, 7102 (37.1%) and 12 060 (62.9%) men were in urban and rural areas, respectively, and 3556 (18.6%), 13 623 (71.1%) and 1983 (10.3%) patients were enrolled from academic centers, non-academic hospitals and urological clinics, respectively. The risks of progression, cancer-specific mortality and all-cause mortality were comparable between urban and rural areas in propensity-score matched analysis. Risks of progression, cancer-specific mortality and all-cause mortality in urological clinics were higher than those in academic centers in propensity-score matched analysis. CONCLUSIONS: Our findings suggest that Japan facility type, but not geographical regions, might affect the prognosis of prostate cancer patients receiving primary androgen deprivation therapy.

Dynamics of conditional survival and risk factors in androgen deprivation therapy for prostate cancer using a multi-institutional Japan-wide database.

OBJECTIVES: The objectives of this study were to analyze the conditional survival and prognostic factors in androgen deprivation therapy for prostate cancer using the Japan Study Group of Prostate Cancer database. METHODS: Data on patients treated with primary androgen deprivation therapy between 2001 and 2003 from a nationwide database of the Japan Study Group of Prostate Cancer were used. The conditional 5-year progression-free rate, cancer-specific survival and overall survival, as well as the conditional mortality owing to prostate cancer and other causes were calculated as per subgroups. Prognostic factors for progression-free rate, cancer-specific survival and overall survival at each time after androgen deprivation therapy initiation were calculated using the Cox proportional hazards model. RESULTS: The conditional 5-year progression-free rate and cancer-specific survival, but not overall survival, gradually increased with time. The prognostic impact of stage IV characteristics (T4, N1 and M1) changed over time; however, the prognostic impact of the Gleason score remained unchanged. In the subgroup analysis, prostate-specific mortality risk reduced over time in patients with stage IV prostate cancer, whereas non-prostate cancer mortality increased over time in elderly patients. CONCLUSIONS: Information regarding conditional survival and mortality obtained in this study would provide a benchmark for physicians and cancer survivors.

[Current Clinical Practice Pattern for Castration-Resistant Prostate Cancer(CRPC)in Japan].

Although various agents are reported against castration-resistant prostate cancer(CRPC), little is known about their actual clinical use in Japan. In this study, 484 patients diagnosed with CRPC during androgen-deprivation therapy were selected from Japan's leading multicenter collaborative research real-world database. The treatment details and prognosis were analyzed. It was observed that the castration treatment represented by the use of LH-RH agonists and antagonists was continued in almost all cases even after CRPC diagnosis. First-line non-castration agents for the CRPC treatment including certain novel agents approved from 2010 onwards and conventional agents used before that were selected for use in 76.5% and 23.5% of cases, respectively, with the 1-year continuation rates being 57.7%, and 52.4%, respectively. The 1.5-year overall survival rate from CRPC was 63.7%(90.0% in the conventional agents' group and 58.8% in the novel agents' group). Previously, conventional agents were sometimes selected for the CRPC treatment; hence, they still seemed to play a role in clinical practice in Japan.

Primary Androgen-Depletion Therapy Prevails Not Only for Metastatic but Also for Nonmetastatic Hormone-Naïve Prostate Cancer in Japan-Recent Trends and Efficacy.

OBJECTIVE: To investigate the real-world use of primary androgen-deprivation therapy(PADT; gonadotropin-releasing hormone agonists[leuprorelin/goserelin]and antagonists[degarelix]/surgical castration), its clinical effectiveness, and the characteristics of Japanese patients with hormone-sensitive prostate cancer treated with PADT. METHODS: In this retrospective, observational study, patients using PADT(≥1 record)in the 2016-2018 Japan Study Group of Prostate Cancer registry were followed up from their initial date of PADT until October 2018. The primary endpoints included prostate-specific antigen( PSA)response rate(PSA<4 ng/mL)and duration of initial treatment. RESULTS: Of 1,895 patients, 47.7%, 24.4%, and 22.0% received leuprorelin, goserelin, and degarelix, respectively; 5.9% underwent surgical castration. The degarelix group had the highest median PSA at diagnosis(116.7 ng/mL)and proportion of patients with clinical Stage Ⅳ prostate cancer (72.9%)and Gleason score 9-10(59.7%). A concomitant antiandrogen was used in >80% and 70% of patients in the leuprorelin/goserelin and degarelix groups, respectively; bicalutamide was used most commonly(99.0%). Median duration of initial treatment was 20.8 months in the degarelix group and not yet reached in the leuprorelin/goserelin groups; continuation rates at 24 months were 44.6% and 81.6%/87.3%, respectively. The PSA response rate was the highest in the leuprorelin group(93.7%); median percentage change in PSA was comparable across all treatment groups(-99.1% to -99.8%). CONCLUSIONS: Real-world use of PADT in patients with hormone-sensitive prostate cancer is likely based on its specific therapeutic attributes and patient characteristics.

A single-institute experience of trimodal bladder-preserving therapy for histologic variants of urothelial carcinoma.

BACKGROUND: We retrospectively evaluated the clinical outcomes of patients with histologic variants of muscle invasive bladder cancer (MIBC) treated with trimodal bladder-preserving therapy (TMT). METHODS: Among 148 patients with clinical T2-3N0M0 MIBC treated with TMT at Tsukuba University Hospital from 1990 to 2015, 11 patients (7.4%) had pathological components of variant urothelial carcinoma (UC). The complete response (CR), overall survival (OS), cause-specific survival (CSS) and progression-free survival (PFS) rates were analyzed in these 11 patients. RESULTS: Among the 11 patients with variant UC, 7 (64%) had UC with squamous and/or glandular differentiation and 4 (36%) had sarcomatoid (n = 1), plasmacytoid (n = 1), signet ring cell (n = 1), or clear cell variant (n = 1). Median follow-up was 49.0 months. Nine (82%) out of 11 patients achieved CR and 2 (22%) out of the 9 developed recurrence. Among seven patients who had UC with squamous and/or glandular differentiation, two developed recurrence and one died of disease. In contrast, 2 (50%) out of four patients with other variants, which were sarcomatoid variant or signet ring cell, developed recurrence and died of disease. Overall, the 5-year OS, CSS, and PFS rates of variant UC were 75%, 75%, and 58%, respectively. CONCLUSIONS: TMT might provide acceptable clinical outcomes for well-selected MIBC patients with histologic variants, especially for those with squamous and/or glandular differentiation. However, we need to pay special attention to other variants such as sarcomatoid variant or signet ring cell. TMT might be an alternative treatment option for patients with histologic variants, although further experiments will be needed to confirm this.

Family history in primary hormone therapy for prostate cancer: Analysis from a community-based multi-institutional Japan-wide database.

OBJECTIVES: To determine the association between hormone therapy and outcomes in a cohort of prostate cancer patients with a family history of prostate cancer. METHODS: Data of patients with prostate cancer who had received hormone therapy were extracted from a nationwide community-based database established by the Japan Study Group for Prostate Cancer. Family history of prostate cancer was available for 13 346 of these patients, who thus comprised the study cohort. Prognostic variables, including progression-free survival, cancer-specific survival and overall survival, were compared between men with familial and men with sporadic prostate cancer. RESULTS: A positive family history was identified in 220 patients (1.6%). Patients with a positive family history were younger than those without; however, other clinicopathological characteristics and prognoses were comparable. In subgroup analysis, family history was identified as a possible favorable prognostic factor for overall survival among patients with a prostate-specific antigen level at diagnosis <100 ng/mL and those with low or intermediate Japan Cancer of the Prostate Risk Assessment. CONCLUSIONS: Our findings show that familial prostate cancer has an early-onset feature or is diagnosed earlier than sporadic prostate cancer. However, the prognosis of individuals with familial prostate cancer undergoing hormone therapy is comparable to those with sporadic prostate cancer.

The resonance® metallic ureteral stent in the treatment of malignant ureteral obstruction: a prospective observational study.

BACKGROUND: To study the outcomes and experiences of using metallic stents in treating patients with malignant ureteral obstruction (MUO), we examined the effects of metallic ureteral stenting using the Cook Resonance® stent in the treatment of MUO. METHODS: All patients who had a Resonance metallic stent inserted between April 2015 and March 2018 at one of multiple facilities were prospectively observed with a 1-year follow-up. The primary outcome was the patency rate of the metallic ureteral stent. The secondary outcomes included the complications (e.g., infection and fever). RESULTS: Although stent insertion was attempted in 50 patients, the stent could not be inserted as a ureteral stent in three patients due to severe ureteral stricture, and one ureteral cancer patient was excluded from the analysis. The remaining 46 patients' median age was 67 years (range 28-85 years) (16 males, 30 females). Twenty-four patients died during the study; their median survival time was 226 days. The median follow-up period for the censored patients was 355 days (range 16-372 days), and just seven patients were still alive without Resonance failure > 1 year later. The women's IPSS scores tended to be lower than those of the men. Regarding the OABSS score, although the women's total score tended to be low, the difference between the men's and women's scores was nonsignificant. The bacteria detected from urine culture after stent insertion were more gram-positive than gram-negative. CONCLUSION: Metallic ureteric stenting using the Resonance stent is safe and effective for treating MUO. Subjective symptoms were relatively less in the female patients.

Bacillus Calmette-Guérin strain differences as the basis for immunotherapies against bladder cancer.

In the past 40 years, intravesical immunotherapy with Mycobacterium bovis bacillus Calmette-Guérin has been carried out as the most effective treatment for preventing local recurrences and tumor progression of non-muscle-invasive bladder cancer. Bacillus Calmette-Guérin is a family of vaccines derived in 1921 by the in vitro attenuation of Mycobacterium bovis. Subsequently, bacillus Calmette-Guérin seed lots were spread around the world, and both phenotypic and genotypic differences among the strains have been compiled. In recent genomic comparisons, the evolution of the different bacillus Calmette-Guérin substrains has begun to emerge. However, some of these genetic alterations in bacillus Calmette-Guérin strains have yet to be shown to affect the therapeutic effects and/or adverse effects. There are thus ongoing research efforts to assess the effects of these genetic alterations on the properties of bacillus Calmette-Guérin strains, with the ultimate goal of identifying an ideal bacillus Calmette-Guérin strain for treatment of non-muscle-invasive bladder cancer and providing clues for the improvement of bacillus Calmette-Guérin strains. The present review provides a history of bacillus Calmette-Guérin immunotherapy, and discusses the genetic differences among bacillus Calmette-Guérin strains, the different clinical outcomes afforded by bacillus Calmette-Guérin strains and possible future developments.

Prostate cancer trends in Asia.

INTRODUCTION: Differences in the incidence and mortality rates for prostate cancer between East and West are clearly defined, with higher rates in the West and lower rates in the East. Treatment methods are generally selected in accordance with general practice guidelines, but the current reality in Asia is that there is not sufficient clinical data to set Asia-specific guidelines for treatment. This leads to a situation whereby for the large part guidelines based on scientific evidence accumulated in Western countries are followed, but from time to time cases are encountered when such guidelines may not be considered to be the most appropriate for the case at hand. METHODS AND RESULTS: Although there is a relatively large volume of clinical evidence relating to endocrine therapy in Asia, the treatment choices and effects differ to those in the West. These regional differences are thought to be due to various factors, including not only differences in genetic background, but also distinct differences in the living and healthcare environments. If the differences between East and West in terms of trends in prostate cancer could be examined, with positive aspects being adopted and negative aspects being improved, this could also be expected to be of use in developing a better treatment strategy for prostate cancer. The exchanging of information on a broader, global level will enable improvements in prevention, diagnosis and treatment of prostate cancer. CONCLUSION: It is in pursuit of this objective that it is important to promote high-quality clinical trials and joint epidemiological studies in Asia and work to accumulate data that are comparable to data available in Western countries.

Validation of TNM classification for metastatic prostatic cancer treated using primary androgen deprivation therapy.

PURPOSE: The current tumor-node-metastasis (TNM) classification system has been used for many years. The prognosis of patients with metastatic prostate cancer (mPC) treated using primary androgen deprivation therapy (PADT) was analyzed according to the TNM classification. METHODS: A total of 5618 cases with lymph node metastases only (N1M0), non-regional lymph node metastasis (M1a), bone metastasis (M1b), and distant metastasis (M1c) were selected from the Japanese Study Group of Prostate Cancer database. Overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) rates were calculated using Kaplan-Meier analysis. The influence of clinical variables on patient prognosis was evaluated using the Cox proportional hazard regression model. RESULTS: The 5-year OS, CSS, and PFS were 76.0, 83.2, and 38.8% in N1M0, 57.5, 69.0, and 23.0% in M1a, 54.0, 63.1, and 23.0% in M1b, and 40.0, 51.5, and 16.6% in M1c, respectively. OS, CSS, and PFS worsened as the stages progressed. OS, CSS, and PFS were all significantly worse in N1M1b compared with N0M1b. Multivariate analysis revealed that OS and CSS were worse in patients with a Gleason score ≥8 and that combined androgen blockade (CAB) treatment provided better OS than non-CAB treatments at any tumor stage. However, OS and CSS were worse in individuals with a prostate-specific antigen >100 ng/ml only in M1b. CONCLUSIONS: Patient prognosis worsened with stage progression; therefore, current TNM classification system of mPC for PADT was shown to be trustworthy. Each PC cell that develops bone or lymphoid metastasis may exhibit different characteristics.

Long-term survival of extremely advanced prostate cancer patients diagnosed with prostate-specific antigen over 500 ng/ml.

OBJECTIVE: To investigate survival of hormone-naïve prostate cancer patients diagnosed with prostate-specific antigen ≥500 ng/ml, stratified according to the prostate-specific antigen level and type of therapy. METHODS: Data of prostate cancer patients with prostate-specific antigen ≥500 ng/ml diagnosed between 2001 and 2003 and receiving primary androgen deprivation therapy were extracted from the Japan Study Group of Prostate Cancer database. Cancer-specific survival and overall survival were assessed according to the prostate-specific antigen level (500-999, 1000-4999 and ≥5000 ng/ml) and type of therapy using Kaplan-Meier analyses and multivariate Cox proportional hazards models including age, Gleason score, oncological stage and comorbidity. RESULTS: The median follow-up was 27 months (interquartile range, 13-51) and a total of 1961 patients were included. Five-year cancer-specific and overall mortalities were 39.0 and 33.0%, respectively. There was a significant inverse relationship between overall survival and prostate-specific antigen magnitude among combination therapy patients, but not monotherapy patients (log-rank test, P = 0.034 and 0.558, respectively). The median overall survival in combination therapy patients with low-, intermediate- and high prostate-specific antigen and monotherapy patients with any prostate-specific antigen were 79, 59, 45 and 43 months, respectively. Multivariate analysis showed that combination therapy in patients with low- and intermediate prostate-specific antigen was significantly associated with a favorable overall survival compared with monotherapy (hazard ratios 0.66 and 0.75, respectively, both P < 0.001). Similar results were obtained for cancer-specific survival. CONCLUSIONS: There are major survival differences in extremely high prostate-specific antigen cases according to the prostate-specific antigen level and hormone therapy type and those patients would benefit notably from combination androgen blockade.

Recent trends in the initial therapy for newly diagnosed prostate cancer in Japan.

OBJECTIVE: The objective of the present study was to investigate the trends over time in the initial treatment of prostate cancer in Japan. METHODS: A total of 8291 patients with newly diagnosed prostate cancer whose treatment started in 2010 were registered in a multi-institutional observational study undertaken nationwide across Japan by the Japan Prostate Cancer Study Group. Each patient's background characteristics and initial treatment were recorded. RESULTS: The median age at diagnosis was 71 years. The proportion of T1c disease was 40.5% and that of M1 disease was 10.4%. The prostate-specific antigen level was <10 ng/ml in 52.0% of the patients. High-, intermediate- and low-risk patients as determined by D'Amico's classification system made up 19.3, 29.8 and 25.9% of the cases, respectively. The initial treatment was androgen depletion therapy in 40.2%, radical prostatectomy in 32.0% (17.3% of these involved laparoscopic prostatectomy), radiation in 21.0% (46.4% of these involved brachytherapy). In cases of organ-confined disease, radical prostatectomy was selected in 39.5%, androgen depletion therapy in 28.0% and radiation in 23.9%. In D'Amico's low-risk group, the proportion treated with radiation was nearly equal to that treated with radical prostatectomy (30.2 and 32.7%, respectively); 73.2% of the radiation treatments involved brachytherapy. CONCLUSION: Compared with previous Japanese studies, radiation use was increased by ∼10%. This increased proportion of radiation use was a typical trend in initial therapy for newly diagnosed prostate cancer cases in Japan. Although androgen depletion therapy use was decreased, it was selected in a high proportion of the patients irrespective of the disease stage.

Prognostic impact of young age on stage IV prostate cancer treated with primary androgen deprivation therapy.

OBJECTIVES: To elucidate whether the disease characteristics and prognosis of stage IV prostate cancer treated with primary androgen deprivation therapy differ between young and elderly patients. METHODS: A total of 3006 patients identified from the database of the Japan Study Group of Prostate Cancer were included in the analysis according to the following entry criteria: age of 75 years or less and stage IV disease. These patients were stratified into three groups: young (aged ≤ 55 years); middle-aged (aged ≧ 56 and ≤ 65 years); and elderly (aged ≧ 66 and ≤ 75 years). Their prognoses were analyzed both within age groups and according to whether or not there was metastasis. RESULTS: The proportion of lymph node metastasis was significantly higher in the young group than in the elderly group (P = 0.007), and there were no significant differences in other factors among age groups. The overall survival rate at 5 years in the young group was significantly worse than that in the middle-aged and elderly groups (26.6%, 59.7% and 55.3%, respectively) in patients with stage IV disease with metastasis, although there was no difference among age groups in patients with stage IV disease without metastasis. Multivariate analysis showed that younger age was an independent strong prognostic factor in stage IV disease with metastasis. CONCLUSIONS: Young men with metastatic prostate cancer have a poor prognosis. Young age is an independent prognostic factor in stage IV metastatic prostate cancer patients treated with primary androgen deprivation therapy.