Real-world data in elderly men from Yokosuka City 15 years after introducing prostate-specific antigen-based population screening.

Mass screening based on prostate-specific antigen (PSA) reduces mortality in prostate cancer. However, the effectiveness of this screening in the elderly has not been demonstrated. In the city of Yokosuka, Japan, PSA screening has been conducted since 2001 and the present study examined the real-world status of PSA-based population screening in the elderly. It retrospectively evaluated 1,117 prostate cancer patients >75 years of age. The patients were divided into two groups: The screened group comprising patients diagnosed by PSA-based population screening or workplace screening and PSA follow-up patients at urology clinics; and the non-screened group comprising patients detected by other methods. Overall survival (OS), cancer-specific survival (CSS) and factors contributing to shorter CSS between the groups were compared. In patients >75 years of age, the screened group had significantly longer OS (171 vs. 154 months; P=0.019) and CSS (median not reached; P=0.020) but screening was not an independent factor associated with prolonged OS or CSS on multivariate analysis. The factors contributing to shorten CSS in the elderly were ≥T3 (odds ratio: 3.301 [1.704-6.369], P<0.001), M1 (odds ratio: 4.856 [2.809-8.393], P<0.001) and Gleason score ≥8 (odds ratio: 4.691 [2.479-8.876], P<0.001). In those with metastasis, PSA screening was not associated with prolonged OS or CSS. Real-world data 15 years after introducing PSA-based population screening was not an independent factor for both OS and CSS in multivariate analyses for patients >75 years of age.

Effect of cisplatin on metastatic castration-resistant prostate cancer with BRCA2 mutation: A case report.

Poly (ADP-ribose) polymerase inhibitors exhibit strong activity for treating the DNA damage repair defect in patients with prostate carcinoma (PCa). Although conventional DNA-damaging agents can theoretically lead to synthetic antitumoral effects, no report has clearly mentioned the clinical use of cisplatin for treating PCa patients with the breast cancer gene (BRCA)2 mutation. We administered 80 mg/m2 cisplatin triweekly to a patient with metastatic castration-resistant PCa (mCRPC) with the BRCA2 mutation, and after ten cycles, the prostate-specific antigen was dramatically decreased. We suggest that BRCA2 mutations may indicate the use of cisplatin for treating patients with mCRPC.

Does screening for prostate cancer improve cancer-specific mortality in Asian men? Real-world data in Yokosuka City 15 years after introducing PSA-based population screening.

BACKGROUND: Studies of prostate-specific antigen (PSA)-based population screening have been conducted in western countries, but there is little data in Asian populations. The objective of this study was to determine the efficacy of PSA screening in Asian men using real-world data over a period of 15 years after introducing population screening in Yokosuka City, Japan. METHODS: We investigated patients with pathologically diagnosed prostate cancer at four hospitals and two clinics across the Yokosuka area (Miura peninsula) between April 2001 and March 2015. Patients were divided into two groups; the S group consisted of those diagnosed by PSA-based population screening in Yokosuka City and the NS group consisted of those diagnosed by methods other than screening. Cancer-specific survival (CSS) and overall survival (OS) rates were calculated using the Kaplan-Meier method with the log-rank test to compare survival between the two groups. Clinical and pathological factors for cancer-specific mortality were assessed with Cox regression analyses to calculate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: A total of 3094 patients had been diagnosed with prostate cancer over the 15-year period. The median follow-up period was 77 months. The S group and the NS group consisted of 977 and 2117 patients, respectively. Patients in the S group were younger (age: 71 years vs 73 years, P < .001) and had a lower Charlson comorbidity index (CCI) with favorable oncological factors, such as lower initial PSA, Gleason score (GS), and risk category. Kaplan-Meier curves for OS and CSS revealed significant differences between the two groups (OS: P < .001, CSS: P < .001). Analysis with Cox proportional hazards model indicated the NS group (HR: 1.584, 95% CI, 1.065-2.356, P = .023), a CCI > 4 (HR: 1.552, 95% CI, 1.136-2.120, P = .006), a GS ≥ 8 (HR: 4.869, 95% CI, 2.631-9.001, P < .001), and nonlocalized cancer (locally advanced; HR: 2.632, 95% CI, 1.676-4.133, P < .001, advanced; HR: 9.468, 95% CI, 6.279-14.278, P < .001) as independent risk factors for cancer-specific mortality. CONCLUSIONS: PSA-based population screening of prostate cancer might be useful in the Japanese population.

Clinical outcomes of prostate cancer patients in Yokosuka City, Japan: A comparative study between cases detected by prostate-specific antigen-based screening in Yokosuka and those detected by other means.

OBJECTIVES: To investigate whether prostate-specific antigen-based screening reduced the prostate cancer mortality rate in Yokosuka, Japan. METHODS: We carried out a cohort study, in which we compared clinical outcomes between patients detected by prostate-specific antigen-based screening (S group n = 524) versus those detected by other means (NS group n = 1044). Clinical and pathological factors were evaluated using Cox regression analyses and the Kaplan-Meier method. RESULTS: A total of 1.5% (8/524) of patients in the S group and 6.7% (70/1044) of those in the NS group died from prostate cancer during follow up. A total of 8.0% (42/524) of patients in the S group and 11.4% (119/1044) in the NS group died from other causes. The 10-year cancer specific survival rates of the S and NS groups were 97% and 86%, respectively (P < 0.001). The median age was significantly lower in the S group than the NS group: 71 and 73 years, respectively (P < 0.001). The rate of Gleason score 8-10 was significantly lower in the S group than the NS group: 9.7% and 16.7%, respectively (P < 0.001). The rate of patients with metastasis or prostate-specific antigen 100 ng/mL or more was significantly lower in the S group than the NS group: 7.8% and 23.0%, respectively (P < 0.001). On multivariate analysis, Gleason score 8-10 compared with Gleason score 6 was independently associated with cancer-specific survival (hazard ratio 4.808, 95% confidence interval 1.044-22.14, P = 0.044). CONCLUSIONS: Prostate-specific antigen-based population screening in Yokosuka City might help to reduce the prostate cancer mortality rate.

[8-month neoadjuvant hormonal therapy before radical prostatectomy for high-risk prostate cancer].

PURPOSE: To evaluate the clinicopathological outcomes of 8 months of neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy for high-risk prostate cancer. PATIENTS AND METHODS: A multi-institutional prospective trial was performed between July 2000 and May 2003 involving high-risk prostate cancer patients without metastasis, including 21 who received 8 months of NHT before radical prostatectomy. High-risk group was defined as clinical stage > or =T2c and/or prostate-specific antigen (PSA) >20 ng/ml and/or Gleason score > or =8. PSA values were considered elevated (biochemical failure) if values of 0.1 ng/ml or greater were obtained. RESULTS: Median of initial PSA levels before prostate biopsy was 27.6 ng/ml (8.5-80.7 ng/ml), and median of pre-operative PSA levels after NHT was 0.28 ng/ml (0.02-4.2 ng/ml). There were 5 patients (23.8%) with lower limit of PSA detection (less than 0.02 ng/ml) in 8 months after NHT. The clinical T stage was T1c in 9 patients (42.9%), T2a-b in 8 patients (38.1%), T2c in 3 patients (14.3%), and T3a in 1 patient (4.8%). The median follow-up was 25 months (range 4 to 37). There were 2 patients (9.5%) in pT0, 5 patients (23.8%) with positive surgical margin, 5 patients (23.8%) with extracapsular extension (ECE) and 3 patients (14.3%) with seminal vesicle involvement (SVI). Biochemical failure was occurred in 9 of 21 (42.9%) including of one pT0. Range of time to postoperative biochemical failure was 2 to 25 months (median 6 months) and most of biochemical failure was found within 12 months after surgery. Biochemical failure rate was significantly higher in patient with positive SVI (p = 0.0308) and higher in patients with pre-operative PSA levels of more than 0.1 ng/ml (p = 0.0836), positive ECE (p = 0.0545) and positive surgical margin (p = 0.0545). CONCLUSION: Biochemical failure was frequent after this combined treatment, even in a pT0 case. Long-term follow-up of patients is needed to assess the impact of this therapy on mortality.

[Arthritis following intravesical instillation of BCG for urothelial cancers].

BACKGROUND: Intravesical instillation of bacillus Calmette-Guerin (BCG) is efficient for prophylaxis of superficial bladder cancer and treatment for carcinoma in situ (CIS) of the upper urethelial cancer. However, the incidence of adverse effects is relatively high, and those include reactive arthritis. We retrospectively evaluated the incidence and the outcome of reactive arthritis following intravesical BCG therapy for urothelial cancers. PATIENTS AND METHODS: Intravesical instillations of BCC were performed in 192 cases (218 courses) between January 1998 and January 2002. BCG was instilled for prophylaxis of superficial bladder cancer recurrence in 170 (195 courses), treatment for CIS in 7 (8 course), and treatment for CIS in 7 (8 courses), and treatment for CIS in upper urinary tract in 15 (15 courses). RESULTS: Arthritis was recognized in 8 cases (3.7%, 8/218 courses), and 7 of them were identical to reactive arthritis following BCG therapy. Remaining 1 patient was diagnosed as rheumatoid arthritis (RA), and the relation between arthritis and intravesical BCG instillation was unclear. Mean number of BCG instillation was 5.6 (3-8 times). All reactive arthritis were occurred within 4 weeks after the last BCG instillation, i.e., BCG induced urinary tract infection, and 6 of them were polyarthritis. Concurrence of conjunctivitis was seen in one patient. HLA-B27 was negative in 4 examined patients. A nonsteroidal anti-inflammatory drug (NSAID) was used in all 8 patients, anti-tuberculous agents were used in 3, and prednisolone was added in 3, Arthritis was improved within 2 months in patients received prednisolone, however, it persisted longer than 3 months in patients without prednisolone. CONCLUSION: Arthritis was recognized in higher incidence than previous reports following intravesical instillation of BCG. All cases except one, diagnosed as RA, were diagnosed as reactive arthritis (Reiter's syndrome). However, correlation between HLA-B27 and arthritis was not clear in this study. Administration of steroidal drug was thought to improve arthritis in shorter duration.

Predicting the presence and side of extracapsular extension: a nomogram for staging prostate cancer.

PURPOSE: We developed a model to predict the side specific probability of extracapsular extension (ECE) in radical prostatectomy (RP) specimens based on the clinical features of the cancer. MATERIALS AND METHODS: We studied 763 patients with clinical stage T1c-T3 prostate cancer who were diagnosed by systematic needle biopsy and subsequently treated with RP. Candidate predictor variables associated with ECE were clinical T stage, the highest Gleason sum in any core, percent positive cores, percent cancer in the cores from each side and serum prostate specific antigen (PSA). Receiver operating characteristic (ROC) analyses were performed to assess the predictive value of each variable alone and in combination. We constructed and internally validated nomograms to predict the side specific probability of ECE based on logistic regression analysis. RESULTS: Overall 30% of the patients and 17% of 1,526 prostate lobes (left or right) had ECE. The areas under the ROC curves (AUC) of the standard features in predicting side specific probability of ECE were 0.627 for PSA, 0.695 for clinical T stage on each side and 0.727 for Gleason sum on each side. When these features were combined predictive accuracy increased to 0.788. The highest value (0.806) was achieved by adding the percent positive cores and the percent cancer in the biopsy specimen to the standard features. The resulting nomograms were internally validated and had excellent calibration and discrimination accuracy. CONCLUSIONS: Standard clinical features of prostate cancer in each lobe-PSA, palpable induration and biopsy Gleason sum-can be used to predict the side specific probability of ECE in RP specimens. The predictive accuracy is increased by adding information from systematic biopsy results. The predictive nomograms are sufficiently accurate for use in clinical practice in decisions such as wide versus close dissection of the cavernous nerves from the prostate.

Counseling men with prostate cancer: a nomogram for predicting the presence of small, moderately differentiated, confined tumors.

PURPOSE: Men diagnosed with clinically localized prostate cancer have a number of treatment options available, including watchful waiting, radical prostatectomy and radiation therapy. With the widespread use of serum prostate specific antigen (PSA) testing, prostate cancers are being diagnosed earlier in their natural history, with many tumors being small and of little health risk to the patient, at least in the short term. To better counsel men diagnosed with prostate cancer, we developed a statistical model that accurately predicts the presence of small moderately differentiated, confined cancer based on clinical variables (serum PSA, clinical stage, prostate biopsy Gleason grade and ultrasound volume) and variables derived from the analysis of systematic biopsies. MATERIALS AND METHODS: The analysis included 409 patients diagnosed by systematic needle biopsy with clinical stages T1c or T2a N0 or NX and M0 or MX prostate cancer who were treated solely with radical prostatectomy at 1 of 2 institutions. Additional biopsy features included number and percentage of biopsy cores involved with cancer and high grade cancer, in addition to total length of biopsy cores involved. Indolent cancer was defined as pathologically organ confined cancer 0.5 cc or less in volume and without poorly differentiated elements. Logistic regression was used to construct several prediction models and the resulting nomograms. RESULTS: Overall 80 (20%) of the patients had indolent cancer. The nomogram predicted the presence of an indolent cancer with discrimination (area under the receiver operating characteristics curves) for various models ranging from 0.64 to 0.79. Calibration of the models appeared good. CONCLUSIONS: Nomograms incorporating pretreatment variables (clinical stage, Gleason grade, PSA and the amount of cancer in a systematic biopsy specimen) can predict the probability that a man with prostate cancer has an indolent tumor. These nomograms have good discriminatory ability and calibration, and may benefit the patient and clinician when the various treatment options for prostate cancer are being considered.

A nomogram to predict seminal vesicle invasion by the extent and location of cancer in systematic biopsy results.

PURPOSE: We determined whether systematic biopsy results increases the accuracy of standard clinical information in predicting seminal vesicle invasion (SVI). MATERIALS AND METHODS: We analyzed a retrospective cohort of 763 patients with clinical stages T1c-T3 prostate cancer who were diagnosed by systematic biopsy and treated with radical prostatectomy. We recorded the location of each biopsy core and measured the length of cancer and total length of each core. Using logistic regression analysis we constructed and internally validated a nomogram to predict SVI. RESULTS: A total of 60 patients (7.9%) had SVI. Cancer was present in a biopsy core from the base in 437 patients, of whom 12.8% had SVI compared with only 1.2% of the 326 without cancer at the base. None of the 275 patients with prostate specific antigen (PSA) 10 ng/ml or less and no cancer at the base had SVI. On multivariate analysis serum PSA (p <0.0005), primary Gleason grade (p = 0.028) and percent cancer at the base (p <0.005) were the only significant predictors of SVI. The predictive accuracy of a standard model that included only stage, grade and PSA was maximally enhanced by including the percent cancer at the base (p = 0.0013). A nomogram that incorporated this variable produced probabilities of SVI that differed from the standard model by +/- 10% in 68% of the cases. CONCLUSIONS: The presence and amount of cancer in systematic needle biopsy cores from the base of the prostate strongly predicts the presence of SVI. Systematic biopsy results enhance the accuracy of nomograms to predict SVI.

Sufficient prophylactic efficacy with minor adverse effects by intravesical instillation of low-dose bacillus Calmette-Guérin for superficial bladder cancer recurrence.

BACKGROUND: Intravesical instillation of bacillus Calmette-Guérin (BCG) is the most efficient strategy for prophylaxis of superficial bladder cancer recurrence. Adverse effects of BCG are major obstacles, but the reduction of BCG dose could minimize these effects. The efficacy and adverse effects of half-dose (40 mg) BCG, Tokyo 172 strain, were prospectively evaluated. METHODS: A total of 93 patients with superficial bladder cancer (pTa or pT1) were sequentially assigned to receive either 40 or 80 mg of BCG after transurethral resection. BCG was administered weekly for 6 weeks postoperatively. Eighty patients observed longer than 12 months after BCG therapy (41, 40 mg group; 39, 80 mg group) were analyzed. RESULTS: BCG therapy course was completed in 71 patients. Tumor recurrence was recognized in 11 of 40 patients in the 40 mg group and in 5 of 31 patients in the 80 mg group. There was no significant difference in tumor recurrence rate between the two groups (P = 0.547). BCG therapy was withdrawn in 1 patient in the 40 mg group and in 8 patients in the 80 mg-group because of BCG-related adverse effects. The morbidity of BCG-related toxicity was significantly higher in the 80 mg group. CONCLUSION: Half-dose of BCG Tokyo 172 strain had a similar efficacy and its toxicity was significantly lower compared to the standard dose. Thus, half-dose of this strain might be suitable, at least for initial BCG therapy, for the prophylaxis of bladder cancer recurrence. Further study would be necessary to clarify the efficacy of low-dose instillation in high-risk patients.

[The 1992 TNM classification of T2 prostate cancer predicts pathologic stage and prognosis better than the revised 1997 classification].

PURPOSE: In the 1997 the TNM staging system for prostate cancer was changed, reclassifying, T2 cancers from 3 groups (T2a, less than one half of one lobe; T2b, one lobe; and T2c, both lobes) to 2 groups (T2a, one lobe; and T2b, both lobes), combining the 1992 T2a and T2b into the 1997 T2a subclassification. We investigated the pathological stage and prognosis of cancers in the 1992 and 1997 subclassification to determine whether this change was warranted. MATERIAL AND METHODS: We studied a consecutive series of 555 patients with clinical stage T2 prostate cancer treated with radical prostatectomy (RP) between 1983 and 1998. We analyzed the clinical, pathological features and PSA non-progression rate after prostatectomy for patients classified according to the 1992 and the 1997 TNM system. Median follow-up was 51.3 months. RESULTS: In the 1992 TNM system T2a tumors were more likely to have a low PSA (5.8 versus 7.2 and 8.1 ng/ml, p = 0.034, p = 0.012), be confined to the prostate (67% versus 45% and 40%, p < 0.001 for both), be poorly differentiated (48% versus 63% and 66%, p = 0.002 for both) and have a low cancer volume (1.22 versus 2.27 and 2.63 cm3, p = 0.005 for both) than T2b and T2c tumors. But there were no significant differences between T2b and T2c. Reflecting these results, the patients with T2a cancer had a significantly better prognosis with 82 +/- 4% PSA non-progression rate at 5 years compared to 68 +/- 4% of patients with T2b and 73 +/- 4% of patients with T2c (p = 0.007, p = 0.048, respectively). In the 1997 TNM system T2a tumors were also different from T2b tumors in terms with the frequency of confined cancer (54% versus 40%, p = 0.006) and cancer volume (1.78 versus 2.63 cm3, p = 0.013). However, the those differences were smaller than those in 1992 system. There were no significant differences between 1997 T2a and T2b cancers in the serum PSA level and the frequency of a poorly differentiated cancer. In fact, the 5-years recurrence-free survival rate for patients with T2a (73 +/- 3%) was identical to that for T2b cancer. In a Cox proportional hazard regression analysis, however, neither the 1992 nor the 1997 TNM staging subclassifications of T2 cancers were independent predictor of PSA non-progression when the age of patient, serum PSA level and biopsy Gleason grade were included in the analysis. CONCLUSION: Since a palpable tumor less than half of one lobe (1992 T2a) has a distinctly different pathological and prognostic significance compared to T2b and T2c cancers, the T2a subclassification should be retained in future revisions of TNM staging system. However, because the digital rectal examination provides limited information, both PSA results and histological grade in a biopsy specimen should be incorporated into future revision of the TNM staging system.