Search

Objectives: The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) 8th edition has proposed micrometastasis as a lymph node metastasis (LN+) of diameter ≤2 mm in prostate cancer. However, supporting evidence has not described. We evaluated LN+ patients' survival after radical prostatectomy (RP) based on the LN maximum tumor diameter (MTD). Methods: Data from 561 LN+ patients after RP and pelvic LN dissection (PLND) treated between 2006 and 2019 at 33 institutions were retrospectively investigated. Patients were stratified by a LN+ MTD cutoff of 2 mm. Outcomes included castration resistance‐free survival (CRFS), metastasis‐free survival (MFS), cancer‐specific survival (CSS), and overall survival (OS). Results: In total, 282 patients were divided into two groups (LN+ MTD >2 mm [n = 206] and ≤2 mm [n = 76]). Patients of LN+ status >2 mm exhibited significantly decreased CRFS and MFS, and poorer CSS and OS. No patients developed CRPC in the LN+ status ≤2 mm group when the PLND number was ≥14. Multivariate analysis showed the number of LN removed, RP Gleason pattern 5, and MTD in LN+ significantly predicted CRFS. Conclusions: Patients of LN+ status ≤2 mm showed better prognoses after RP. In all the patients in the ≤2‐mm group, the progression to CRPC could be prevented with appropriate interventions, particularly when PLND is performed accurately. Our findings support the utility of the pN substaging proposed by the AJCC/UICC 8th edition; this will facilitate precision medicine for patients with advanced prostate cancer. [ABSTRACT FROM AUTHOR]

Objectives: The use of radical prostatectomy is increasing with the rising incidence of prostate cancer. We assessed the surgical trends related to radical prostatectomy using data from a multi‐center, retrospective cohort study, the MICAN (Medical Investigation Cancer Network) study, which was conducted in all the urology‐related medical facilities in Ehime Prefecture, Japan. Methods: We compared data from the MICAN study with prostate biopsy registry data collected in Ehime between 2010 and 2020 and recorded the surgical trends. Results: There was a significant increase in the mean age of patients with positive biopsies, and the positivity rate increased from 46.3% in 2010 to 60.5% in 2020, while the number of biopsies obtained decreased. The number of radical prostatectomies performed increased over the years, with robot‐assisted radical prostatectomy becoming the predominant procedure. In 2020, robot‐assisted radical prostatectomies accounted for 96.0% of the surgeries performed. The age at surgery also gradually increased. Of the registered patients aged ≤75 years, 40.5% underwent surgery in 2010, compared with 83.1% in 2020. The prevalence of surgery also increased from 4.6% to 29.8% in patients aged >75 years. There was a gradual increase in the proportion of high‐risk cases, from 29.3% to 44.0%, but a decrease in that of low‐risk cases, from 23.8% in 2010 to 11.4% in 2020. Conclusions: We have shown that the number of radical prostatectomies performed in Ehime is increasing in patients aged both ≤75 and >75 years. The proportion of low‐risk cases has decreased, while that of high‐risk cases has increased. [ABSTRACT FROM AUTHOR]

Purpose: The study was performed to examine patient-reported outcomes (PROs) in the 1st year after surgery and the institutional learning curve after the introduction of robot-assisted radical prostatectomy (RARP). Materials and Methods: The subjects were 320 consecutive patients who underwent RARP from 2014 to 2018. These cases were divided into three groups treated in the early, middle, and late periods, with about 100 cases in each. PROs were recorded using the Expanded Prostate Cancer Index Composite (EPIC). Results: There were no significant differences among the early, middle, and late periods based on EPIC scores. Urinary function and bother decreased in the 1st month after surgery, and gradually recovered thereafter. However, urinary function was significantly worse in the 1st year after surgery than at baseline. Urinary function and bother were better in patients treated with nerve-sparing surgery, and in nerve-sparing cases, urinary function and bother were best in the early period and worst in the late period. These cases also had the best score for sexual function in the early period, but sexual bother was worst in the early period. In contrast, in cases treated without nerve-sparing surgery, urinary function and bother were best in the late period and worst in the early period, although without significant differences. Conclusion: The functional results of this study based on PROs are useful for providing information for patients. Interestingly, the institutional learning curves for RARP differed in cases that did and did not undergo a nerve-sparing procedure. [ABSTRACT FROM AUTHOR]

Objective: Novel androgen receptor axis‐targeted agents (ARATAs) have been developed for mCRPC and improved overall survival (OS). Here, we aimed to find predictors who will receive the greatest benefits from ARATAs. Methods: We previously performed a multicenter study to identify prognostic factors for metastatic hormone‐sensitive prostate cancer (mHSPC, n = 148) and mCRPC (n = 99), and showed that the bone scan index (BSI) was one of the significant prognostic factors for 3‐year OS (PROSTAT‐BSI study). mHSPC progressed to mCRPC (n = 101), for which 69 patients were treated with (n = 39) or without ARATAs (n = 30, prior to the approval of ARATAs). The 69 patients were divided into two groups according to patient factors, and these cohorts were further divided into two subgroups by usage of ARATAs. OS was compared between subgroups in each group. Results: The predictors were age (<71.4 years), serum levels of C‐reactive protein (≥0.16 ng/ml) and alkaline phosphatase (≥548 U/L), time to PSA progression after ADT (<8.9 months), the lowest PSA level (≥1 ng/ml) after ADT, and the rate of PSA decline 3 months after ADT (<0.987), whereas hemoglobin levels, PSA before ADT, Gleason scores, existence of visceral metastases, and BSI were not. Conclusions: The present study identified predictors for the effectiveness of ARATAs. The number of bone metastases (≒BSI), existence of visceral metastases, and Gleason scores, which were identified as high‐risk factors in the LATITUDE study and disease volume in CHAARTED criteria, did not appear to be useful for predicting effectiveness from ARATAs. [ABSTRACT FROM AUTHOR]

Objective: To determine prognostic factors including the Bone Scan Index in prostate cancer patients receiving standard hormonal therapy and chemotherapy. Methods: This multicenter Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan Index study involved 30 hospitals and enrolled 247 patients (age 71 ± 8 years) with metastatic hormone‐sensitive prostate cancer (n = 148) under hormone therapy and metastatic castration‐resistant prostate cancer (n = 99) under chemotherapy. The Bone Scan Index (%) was determined by whole‐body bone scintigraphy using 99mTc‐methylenediphosphonate. Patients were classified into tertiles and binary groups, and predictors of all‐cause death including Bone Scan Index, prostate‐specific antigen, and bone metabolic markers were determined using survival and proportional hazard analyses. Results: During a mean follow‐up period of 716 ± 404 days, 81 (33%) of the patients died, and 3‐year mortality rates were 20% and 52% in the metastatic hormone‐sensitive prostate cancer and metastatic castration‐resistant prostate cancer groups, respectively. Survival analysis showed that a Bone Scan Index >3.5% was a significant determinant of death in the metastatic hormone‐sensitive prostate cancer group, whereas prostate‐specific antigen >55 ng/mL before chemotherapy was a determinant of prognosis in the metastatic castration‐resistant prostate cancer group. A Bone Scan Index >3.5% was also associated with a high incidence of prostate‐specific antigen progression in the metastatic hormone‐sensitive prostate cancer group. Patients with metastatic hormone‐sensitive prostate cancer and a better Bone Scan Index response (>45%) to treatment had lower mortality rates than those without such response. Conclusion: The Bone Scan Index and hot spot number are significant determinants of 3‐year mortality, and combining the Bone Scan Index with prostate‐specific antigen should contribute to the management of prostate cancer patients with bone metastasis. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the health-related quality of life (HRQoL) of Japanese men on active surveillance (AS) in the Prostate cancer Research International Active Surveillance study in Japan (PRIAS-JAPAN). Methods: Participants were included in the PRIAS-JAPAN HRQoL study between January 2010 and March 2016. Their general HRQoL was assessed using a validated Japanese version of the Short-Form 8 Health Survey (SF-8) at enrolment and annually thereafter until discontinuation of AS. The SF-8 mental component summary (MCS) and physical component summary (PCS) of men on AS were compared with scores of the general population (norm-based score [NBS]: 50) and MCS and PCS scores for men following AS were analysed over time. We tested whether MCS and PCS scores over time explained discontinuation of AS. Results: Five hundred and twenty-five patients enrolled, and the median age at baseline was 68 years. At enrolment and after 1-, 2-, and 3-year follow-ups, the PCS and MCS scores were significantly higher than the NBS of the general Japanese population except for the median PCS at 3 years. We found that age at diagnosis and time on AS negatively affected the PCS score of men on AS, while every additional year on AS led to a 0.27 point increase in MCS scores. Neither PCS nor MCS were predictors for discontinuation of AS. Conclusion: Japanese men following an AS strategy for 3 years reported better HRQoL compared with the general population, indicating that monitoring Japanese low-risk prostate cancer patients can be an effective treatment strategy. Study registration: Clinical trial registry—UMIN (University Hospital Medical Information Network); UMIN000002874 (2009/12/11) [ABSTRACT FROM AUTHOR]

Background: We evaluated patient‐reported outcomes (PRO) during neoadjuvant androgen deprivation therapy (ADT) plus external beam radiation therapy (EBRT) followed by either adjuvant continuous ADT (CADT) or intermittent ADT (IADT) for patients with locally advanced prostate cancer (Pca). Methods: A multicenter, randomized phase III trial enrolled 303 patients with locally advanced Pca. The patients were treated with 6 months (M) of ADT followed by 72 Gy of EBRT, and were randomly assigned to CADT or IADT after 14 M. The PROs were evaluated at sic points: baseline, 6 M, 8 M, 14 M, 20 M, and 38 M using FACT‐P questionnaires and EPIC urinary, bowel, and sexual bother subscales. Results: The FACT‐P total scores were significantly better (p < 0.05) in IADT versus CADT at 20 M (121.6 vs.115.4) and at 38 M (119.9 vs. 115.2). The physical well‐being scores (PWB) were significantly better (p < 0.05) in IADT versus CADT at 38 M (25.4 vs. 24.0). The functional scores were significantly better in IADT than those in CADT at 14 M (20.2 vs18.7, p < 0.05) and at 20 M (21.0 vs.18.9, p < 0.05). Conclusion: The PRO was significantly favorable in IADT on FACT‐P total score at 20 M and 38 M, PWB and functional scores at 38 M. [ABSTRACT FROM AUTHOR]

Background: To date, research has not determined the optimal procedure for adjuvant androgen deprivation therapy (ADT) in patients with locally advanced prostate cancer (PCa) treated for 6 months with neoadjuvant ADT and external-beam radiation therapy (EBRT).Methods: A multicenter, randomized, phase 3 trial enrolled 303 patients with locally advanced PCa between 2001 and 2006. Participants were treated with neoadjuvant ADT for 6 months. Then, 280 patients whose prostate-specific antigen levels were less than pretreatment levels and less than 10 ng/mL were randomized. All 280 participants were treated with 72 Gy of EBRT in combination with adjuvant ADT for 8 months. Thereafter, participants were assigned to long-term ADT (5 years in all; arm 1) or intermittent ADT (arm 2). The primary endpoint was modified biochemical relapse-free survival (bRFS) with respect to nonmetastatic castration-resistant prostate cancer (nmCRPC) progression, clinical relapse, or any cause of death.Results: The median follow-up time after randomization was 8.2 years. Among the 136 and 144 men assigned to trial arms 1 and 2, respectively, 24 and 30 progressed to nmCRPC or clinical relapse, and 5 and 6 died of PCa. The 5-year modified bRFS rates were 84.8% and 82.8% in trial arms 1 and 2, respectively (hazard ratio, 1.132; 95% confidence interval, 0.744-1.722).Conclusions: Although modified bRFS data did not demonstrate noninferiority for arm 2, intermittent adjuvant ADT after EBRT with 14 months of neoadjuvant and short-term adjuvant ADT is a promising treatment strategy, especially in a population of responders after 6 months of ADT for locally advanced PCa. [ABSTRACT FROM AUTHOR]

Background: The goals of the study were to examine surveillance biopsy and active treatment in patients under active surveillance (AS) for low-risk prostate cancer and to determine the active treatment-free survival rate. Methods: The subjects were 87 patients with low-risk prostate cancer who were under AS between 2000 and 2010. The eligibility criteria for AS were T1c, Gleason score ≤6, prostate-specific antigen level ≤10 ng/ml, one or two positive biopsies, maximum cancer involvement ≤50 %, and age ≤80 years old. Results: Of the 87 patients, 48 underwent the first surveillance biopsy (55.2 %). In this biopsy, no cancer was found in 33.3 % of cases, 27.1 % remained eligible for AS, and 39.6 % did not meet the AS criteria (up-grade 22.9 %, up-volume 16.7 %). A second surveillance-biopsy was performed at 1.9 years after the first biopsy. No cancer was found in 20.0 % of cases, 40.0 % remained eligible for AS, and 40.0 % did not meet the AS criteria (up-grade 26.7 %, up-volume 13.3 %). A total of 50 patients received treatment by 1.7 years after starting AS, mainly due to an up-grade or up-volume. However, some patients underwent radiotherapy despite biopsy results indicating no cancer or eligibility for AS. The active treatment-free survival rate was 64.1 % after 2 years. Conclusions: Surveillance biopsy is important for identifying patients who require active treatment. The results in this study allowed determination of the active treatment-free survival rate and are informative for making treatment decisions. [ABSTRACT FROM AUTHOR]

Objectives: To examine the association between cancer location, resection margins and oncological outcome in patients undergoing radical prostatectomy. Methods: A total of 505 patients who underwent radical prostatectomy between 1993 and 2009 were included in this analysis. Cancer location, resection margins and pathological factors were assessed based on the 2010 General Rules for Clinical and Pathological Studies on Prostate Cancer. Biochemical recurrence was defined as prostate-specific antigen >0.2 ng/mL. Results: Positive resection margins were found in 38.4% of all cases, in 30.3% of pT2 cases and in 57.7% of pT3 cases. The cancer was distributed evenly among the apex-anterior, apex-posterior and middle lesions, which each accounted for approximately 30% of the whole lesion in the main tumor. A higher rate of positive resection margins (47.6%) was found in the apex-anterior lesions. In minor tumors, most cancer was located in the middle lesion and accounted for approximately 60% of the lesion. However, positive resection margins were detected significantly more frequently in the apex-anterior lesion of minor tumors. The 5-year and 10-year biochemical recurrence-free survival rates were 36.2% and 32.0%, respectively, in patients with a positive resection margin, and 82.7% and 77.4%, respectively, in those with a negative resection margin. Cancer location was an independent risk factor for biochemical recurrence and a positive resection margin. Recurrence-free survival was lower in pT2 cases with a positive resection margin compared with pT3 cases with a negative resection margin. Conclusions: Cancer location and occurrence of positive resection margins can have negative effects on recurrence-free survival. Thus, it is of utmost importance to avoid positive resection margins during radical prostatectomy. [ABSTRACT FROM AUTHOR]

Objectives: To examine quality of life (QOL) for 3 years after radical retropubic prostatectomy (RRP) or permanent prostate brachytherapy (PPB) and to determine differences between the two procedures. Methods: In all 107 patients who underwent RRP and 91 who received PPB between October 2005 and July 2007 were included in this study. QOL surveys were performed using the international prostate symptom score (IPSS), the Medical Outcome Study 8-items short form health survey and the expanded prostate cancer index composite at baseline and 1, 3, 6, 12 and 36 months after treatment. Results: At 3 years, all parameters for general QOL and almost all for disease-specific QOL were similar to those at 12 months. Urinary continence after RRP slightly improved from 12 months to 3 years, but it was still significantly worse than that after PPB. Scores for urinary irritation or obstruction and for bowel function and bother at 3 years were similar between the two groups. Sexual function and bother did not change between 12 months and 3 years in either group. Sexual function at 3 years after RRP was worse than that after PPB. Recovery from urinary incontinence and sexual function after RRP with nerve sparing were similar to those after PPB. Urinary incontinence at 3 years correlated with the treatment method and patients' age, whereas urinary irritation/obstruction and urinary bother correlated with the pre-treatment IPSS. Conclusion: QOL assessment represents an important issue in prostate cancer management. Our findings are likely to be of aid in the development of a treatment plan for prostate cancer patients. [ABSTRACT FROM AUTHOR]

AbstractBackground: The purpose of the present study was to evaluate the antitumor activity and toxicity of oral estramustine phosphate (EMP) in combination with oral etoposide in patients with hormone-refractory prostate cancer. Methods: Twenty patients with adenocarcinoma of the prostate that progressed after one or more regimens of androgen-deprivation therapy were enrolled into this trial. Oral EMP was administered twice daily, for a total daily dose of 560 mg, and oral etoposide (50 mg/bodyweight per day) was given on days 1–21 and was stopped on days 22–35. Treatment was continued until evidence of disease progression appeared or two consecutive rises in the prostate-specific antigen (PSA) value were observed. Results: Ten of 20 patients showed a decrease of 50% or greater in the PSA value from initially elevated PSA levels after therapy. The median progression-free duration and 2 year cause-specific survival rate of these 10 patients were 208 days (range 71–693 days) and 67.5%, respectively. There were no significant differences in age, pretreatment PSA value, duration from initial treatment to relapse, prior therapy or survival between patients who had a decrease of 50% or greater in PSA values after this combination therapy and those who did not. The main toxicities (≥ grade 2) were anemia, leukocytopenia, thrombocytopenia, gastrointestinal and hepatic disorders, which occurred in 40, 15, 10, 15 and 5% of patients, respectively. Conclusions: The combination of oral EMP and etoposide is considered to be a well-tolerated outpatient treatment regimen for patients with hormone-refractory prostate cancer and the therapy deserves further investigation. [ABSTRACT FROM AUTHOR]

Objective Patients and Methods Results Conclusion To report the outcomes of repeat biopsies, metastasis and survival in the Prostate Cancer Research International: Active Surveillance (PRIAS)‐JAPAN study, a prospective observational study for Japanese patients, initiated in 2010.At the beginning, inclusion criteria were initially low‐risk patients, prostate‐specific antigen (PSA) density (PSAD) <0.2, and ≤2 positive biopsy cores. As from 2014, GS3+4 has also been allowed for patients aged 70 years and over. Since January 2021, the age limit for Gleason score (GS) 3 + 4 cases was removed, and eligibility criteria were expanded to PSA ≤20 ng/mL, PSAD <0.25 nd/mL/cc, unlimited number of positive GS 3 + 3 cores, and positive results for fewer than half of the total number of cores for GS 3 + 4 cases if magnetic resonance imaging fusion biopsy was performed at study enrolment or subsequent follow‐up. For patients eligible for active surveillance, PSA tests were performed every 3 months, rectal examination every 6 months, and biopsies at 1, 4, 7 and 10 years, followed by every 5 years thereafter. Patients with confirmed pathological reclassification were recommended for secondary treatments.As of February 2024, 1302 patients were enrolled in AS; 1274 (98%) met the eligibility criteria. The median (interquartile range) age, PSA level, PSAD, and number of positive cores were 69 (64–73) years, 5.3 (4.5–6.6) ng/mL, 0.15 (0.12–0.17) ng/mL, and 1 (1–2), respectively. The clinical stage was T1c in 1089 patients (86%) and T2 in 185 (15%). The rates of acceptance by patients for the first, second, third and fourth re‐biopsies were 83%, 64%, 41% and 22%, respectively. The pathological reclassification rates for the first, second, third and fourth re‐biopsies were 29%, 30%, 35% and 25%, respectively. The 1‐, 5‐ and 10‐year persistence rates were 77%, 45% and 23%, respectively. Six patients developed metastasis, and one patient died from prostate cancer.Pathological reclassification was observed in approximately 30% of the patients during biopsy; however, biopsy acceptance rates decreased over time. Although metastasis occurred in six patients, only one death from prostate cancer was recorded. [ABSTRACT FROM AUTHOR]