The role of single instillation chemotherapy in patients who receive subsequent bacillus Calmette-Guérin: A retrospective single centre study, and systematic review of the literature.

INTRODUCTION: This retrospective study was undertaken to evaluate the combined effect of immediate intravesical chemotherapy and subsequent bacillus Calmette-Guérin (BCG) therapy. METHODS: The study population consisted of 207 intermediate- or high-risk patients with non-muscle invasive bladder cancer who underwent an induction course of BCG between 1993 and 2007. We introduced single immediate instillation of 50 mg epirubicin for all cases in 2004, and thus earlier cases could be considered as historical controls. The primary endpoint was recurrence-free survival (RFS). For cumulative analysis, we systematically reviewed studies indexed in databases. Including ours, the records of 856 patients from a total of 7 studies, including ours, were finally analyzed. RESULTS: In our cohort, the 5-year RFS in patients who received the combination therapy was 66.2%, compared to 55.2% in the BCG alone group (p = 0.149). Multivariate analysis on tumour recurrence showed that patients with the combination therapy had a hazard ratio (HR) of 0.74 (p = 0.189). A subsequent literature review revealed that RFS rates in the combination groups were higher than those in the corresponding BCG alone groups in 4/7 studies (p = 0.02-0.15), and lower in 1 study (p = 0.51). We identified 5 studies which examined a HR for combination therapy, and performed a cumulative analysis. Adding a single chemo-instillation prior to BCG resulted in a significant reduction in tumour recurrence (summary HR 0.69, p = 0.010). CONCLUSIONS: Our analysis suggested that the combination of single chemo-instillation with subsequent BCG therapy exhibited an additive effect against potential tumour recurrence.

Preoperative parameters to predict incidental (T1a and T1b) prostate cancer.

INTRODUCTON: Prostate cancer has been found incidentally in transurethral resection of the prostate (TURP) specimens without prior diagnosis in 5% to 13% of the patients. We evaluated whether incidental prostate cancer (stages T1a and T1b) could be predicted preoperatively. METHODS: TURP was performed in 307 patients between 2006 and 2011. Patient age, prostate-specific antigen (PSA) level, total prostate volume, transitional zone volume, PSA density, history of needle biopsy, and pathological diagnosis on TURP specimen were assessed. We analyzed the association between these parameters and prostate cancer detection. RESULTS: Incidental prostate cancer was found in 31 patients (10.1%), and 13 cases (4.2%) had cancer with T1b and/or Gleason ≥7. Multivariate analysis demonstrated that age ≥75 years (odds ratio [OR] 2.58, p = 0.022), prostate volume ≤50 cc (OR 4.11, p < 0.001), and the absence of preoperative needle biopsy despite PSA ≥4 ng/mL (OR 2.65, p = 0.046) were independent risk factors. In patients who had 2 or 3 of these risk factors, incidental prostate cancer and cancer with T1b and/or Gleason ≥7 were observed in 25% to 50% and 16% to 25% cases, respectively. CONCLUSIONS: Older patient age, small prostate volume, and the absence of previous needle biopsy (despite a high PSA level) might be independent risk factors for detecting incidental prostate cancer, although external validation is warranted to confirm our results.

Third-line hormonal therapy to treat prostate cancer relapse after initial and second-line hormonal therapy: report of 52 cases and literature review.

The aim of this study was to evaluate the efficacy of third-line combined androgen blockade (CAB) therapy for castration-resistant prostate cancer that relapsed after primary and second-line CAB. We retrospectively reviewed the medical records of 52 patients who received first-, second-, and third-line CAB therapy (medical or surgical castration, plus steroidal antiandrogen of chlormadinone acetate, or nonsteroidal antiandrogen of flutamide or bicalutamide). For cumulative analysis, we searched the PubMed database and identified a total of 50 cases published in English. Including our cases, this provided a total of 102 cases for analysis. In our study cohort, 11 cases (21.2%) achieved more than 50% reduction of serum prostate-specific antigen (PSA) on initiation of third-line CAB. We found that third-line CAB with nonsteroidal antiandrogen after second-line CAB with steroidal antiandrogen exhibited favorable results, with a positive response in six of 13 patients (46.2%). Cumulative analysis findings were comparable. Regarding the timing of third-line CAB administration, 15 patients had started at a PSA equal to or less than 4.0 ng/ml, and eight of them (53.3%) showed a positive response to treatment, compared to only three of 37 patients (8.1%) whose PSA at the initiation of third-line therapy was higher than 4.0 ng/ml (p<0.001). We conclude that third-line CAB with nonsteroidal antiandrogen would be particularly useful for patients whose cancer progressed after second-line CAB with steroidal antiandrogen. The timing of treatment seems to be important because the higher the PSA at the start of third-line therapy, the lower the PSA response rate.

Survival following primary androgen deprivation therapy for localized intermediate- or high-risk prostate cancer: comparison with the life expectancy of the age-matched normal population.

The representative guidelines do not recommend androgen deprivation therapy (ADT) as a primary treatment for localized prostate cancer. However, in clinical practice, the use of primary ADT for localized prostate cancer has been widespread, especially among older patients. We performed a retrospective review of the efficacy of primary ADT for localized prostate cancer and compared their outcomes with the life expectancy of the normal population. The study cohort consisted of 410 men diagnosed with localized intermediate- or high-risk prostate cancer over the period 1992-2012 at five institutions. All patients underwent ADT as a primary cancer therapy, and mean follow-up was 6.0 years. Their progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS) rates were calculated. Patients' expected survival rates were estimated by the Hakulinen method. Multivariate analysis demonstrated that Gleason score ≥8 and cT3a were independent risk factors for all of PFS, CSS, and OS. In patients who have none or one of these risk factors, minimum OS rates were not inferior to the expected survival curves of the normal population. Meanwhile, in patients with both risk factors, the OS curve fell below the expected survival rates, especially after 6 years of follow-up. We conclude that primary ADT might be one of the therapeutic options for localized intermediate- and high-risk prostate cancer. However, for high-risk cases with Gleason score ≥8 and cT3a, the choice of primary ADT should be deliberated carefully because the OS of these cases was inferior to the expected survival, especially at a late time point.

Efficacy of tegafur-uracil (UFT) administration in castration-resistant prostate cancer patients with a history of both alternative antiandrogen therapy and estramustine phosphate sodium hydrate therapy.

PURPOSE: The purpose of this study was to evaluate the efficacy of tegafur-uracil (UFT) administration as a fourth-line therapy in patients with castration-resistant prostate cancer (CRPC) who had already received combined androgen blockade (CAB) therapy (first-line), alternative antiandrogen therapy (second-line), and estramustine phosphate sodium hydrate (EMP) therapy (third-line), in order to determine who would benefit from UFT therapy. METHODS: UFT was administered at a daily dose of 300 mg/m(2) to 26 patients, and the response to UFT 4 weeks after its induction and its toxicity were evaluated. RESULTS: A reduction in the serum prostate-specific antigen (PSA) value was observed in 12 patients (46.2 %), while two cases (7.7 %) achieved more than 50 % reduction in PSA. Two patients (7.7 %) required discontinuation of UFT administration because of side effects (grade 2 exanthema in one patient and grade 2 nausea in one patient). A PSA response to UFT was observed, especially in patients older than 75 years and/or whose Gleason score was 8 or less. CONCLUSIONS: Our data indicate that UFT administration as a fourth-line therapy was tolerable and effective to some degree in patients with CRPC who had already received CAB therapy, alternative antiandrogen therapy, and EMP therapy. It can be used, even in patients aged more than 75 years old, without any loss of efficacy or effect on their activities of daily life, and can be regarded as a treatment option for patients with advanced prostate cancer.

Efficacy of estramustine phosphate sodium hydrate (EMP) monotherapy in castration-resistant prostate cancer patients: report of 102 cases and review of literature.

This retrospective chart review study was conducted to evaluate the efficacy of estramustine phosphate sodium hydrate (EMP) monotherapy in patients with castration-resistant prostate cancer (CRPC) and to determine who would benefit from EMP therapy. EMP was administered at a daily dose of 560 mg to 102 patients as a third-line therapy, who had already received combined androgen blockade (CAB) and subsequent alternative antiandrogen therapy. The responses to EMP after its induction and its toxicity were evaluated. We also analyzed the association between the clinicopathological factors of the patients and their responses to EMP therapy. A reduction in the serum prostate-specific antigen (PSA) 4 weeks after induction was observed in 70 patients (68.6%), while 30 cases (29.4%) achieved more than 50% reduction of PSA. Long-term reduction of PSA from baseline for more than 6 months was observed in 31 patients (30.4%). EMP treatment was discontinued in 11 patients (10.8%) because of side effects (nausea in six patients, gynecomastia in three patients, eruption in one patient, and liver dysfunction in one patient). Multivariate analysis demonstrated that long duration of prior hormonal therapy was an independent favorable factor for reduced PSA levels, long responses, and overall survival. The data suggest that oral EMP administration as a third-line monotherapy is well tolerated and effective to some degree in patients with CRPC who have already received CAB and subsequent alternative antiandrogen therapy. Thus, EMP can be regarded as one treatment option, especially for patients whose prior duration of hormonal therapy was long.

The type of patients who would benefit from anti-androgen withdrawal therapy: could it be performed safely for aggressive prostate cancer?

This study was designed to detect the factors that were significantly associated with the results of anti-androgen withdrawal (AAWD) therapy, and to examine whether patients with aggressive prostate cancer demonstrating a short prostate-specific antigen (PSA)-doubling time (DT) could benefit from it without even greater exacerbation of the disease. We conducted a retrospective chart review study of 121 patients who received AAWD therapy due to failed combined androgen blockade (CAB) therapy. A reduction in the serum PSA level after AAWD was observed in 35 patients (28.9 %), and a greater than 50 % decrease from the baseline serum PSA level was observed in 16 patients (13.2 %). Shortening of PSA-DT after AAWD was observed in 48 patients (39.7 %). Univariate and multivariate analyses demonstrated that only a long duration of prior anti-androgen treatment was selected as a significant predictor for a good response to AAWD therapy. With respect to exacerbation after AAWD, we found that patients with a short baseline PSA-DT conversely had a low risk of subsequent shortening of PSA-DT. Using these two factors, we could stratify the patients into four groups, and patients with prior duration of anti-androgen >18 months and PSA-DT ≤3 months demonstrated the best results with a good response rate (67.9 %) and a low risk for a worsening of the disease (14.3 %). We conclude that AAWD would be effective especially for patients whose cancer progressed rapidly (short PSA-DT) after a long stable period under CAB and should be recommended before embarking on the next therapeutic maneuver.

Positive posterior margin of needle biopsy cores is an independent predictor for extracapsular extension in retropubic radical prostatectomy.

OBJECTIVE: To introduce the new preoperative parameter as a predictor for extracapsular extension (ECE), we defined the presence of tumor at the stump of the rectum side on prostate needle biopsy as a positive posterior margin (PPM), and speculated that PPM is related to ECE. METHODS: This retrospective study was conducted in 230 patients who underwent prostate needle biopsy and retropubic radical prostatectomy between 2001 and 2011. We analyzed the association between their clinicopathological parameters and ECE. RESULTS: Multivariate analysis showed that the Gleason score (P = .023, odds ratio [OR] 1.433), serum prostate-specific antigen (PSA, P = .013, OR 1.040), clinical stage (P = .018, OR 2.162), and PPM (P = .013, OR 2.253) were significant independent predictors for ECE. Next, using these 4 preoperative risk factors, we were able to accurately predict their ECE. Patients with 0 or 1 risk factor had a low probability of ECE (13.0% and 18.5%, respectively). In contrast, the majority of patients who had 3 or 4 risk factors were found to have ECE (80.1% and 71.4%, respectively). CONCLUSION: The data suggest that the Gleason score, serum PSA, clinical stage, and PPM may be independent predictors for the existence of ECE. This suggests that the posterior margin in biopsy specimens is a more reliable and clinically useful parameter when making decisions concerning the choice of treatments.

Who Would Benefit from Solifenacin Add-On Therapy to Tamsulosin for Overactive Bladder Symptoms Associated with Benign Prostatic Hyperplasia?

OBJECTIVES: We evaluated the types of patient factors that influence the efficacy and safety of solifenacin add-on therapy to tamsulosin in men with overactive bladder (OAB) associated with benign prostatic hyperplasia (BPH). METHODS: A total of 130 BPH patients with persistent OAB symptoms despite undergoing alpha1-adrenagic antagonist monotherapy were enrolled in this study. Their OAB symptoms persisted after monotherapy consisting of tamsulosin 0.2 mg once daily for more than 8 weeks, followed by subsequent solifenacin 5 mg once daily. The patient backgrounds were assessed, as were the changes in their International Prostate Symptom score (IPSS), Quality of Life (QOL) index, and Overactive Bladder Symptom Score (OABSS) before and 8 weeks after the administration of solifenacin. RESULTS: Total IPSS, QOL index, and OABSS improved significantly following solifenacin administration. Multivariate analyses revealed prostate volume was the only predictor that contributed to the improvement of total IPSS. In patients with prostate volume <30 mL, the improvement in total IPSS (-3.5) was superior to that for prostate volume >30 mL (-0.5; P = 0.002). The data also demonstrated that diabetes mellitus was an independent factor preventing OABSS improvement. In patients with diabetes mellitus, OABSS was not sufficiently improved (-0.6) compared to patients without diabetes (-2.1; P < 0.001). CONCLUSION: Solifenacin add-on therapy to tamsulosin showed efficacy and good tolerability in BPH patients with OAB symptoms. The findings also indicated that patients with a relatively small prostate and without diabetes mellitus would receive more benefit from this therapy.

Risk of subsequent tumour recurrence and stage progression in bacille Calmette-Guérin relapsing non-muscle-invasive bladder cancer.

UNLABELLED: What's known on the subject? and What does the study add? So far, few previous reports have analysed the risk factors for tumour recurrence and stage progression with a special focus on BCG-relapsing disease, defined as the recurrence after achieving a disease-free status by initial BCG instillations for 6 months. There are no guidelines outlining a specific treatment strategy for BCG-relapsing disease, although many BCG failure cases are attributable to BCG-relapsing disease. In this study, additional BCG instillation was shown to decrease the subsequent tumour recurrence rate against BCG-relapsing tumours with intermediate pathological risk features; however, a BCG-relapsing tumour with a pathologically high risk was a significant risk factor for both subsequent tumour recurrence and stage progression. This information might identify a therapeutic strategy for BCG-relapsing tumours. OBJECTIVE: • To investigate the risk of subsequent tumour recurrence and stage progression in bacillus Calmette-Guérin (BCG)-relapsing non-muscle-invasive bladder cancer, defined as recurrence after achieving a disease-free status for 6 months. PATIENTS AND METHODS: • A total of 183 patients with BCG-relapsing tumours were treated with conservative therapy between 1985 and 2008 at our three institutions. • We analysed the association between their clinicopathological parameters and subsequent tumour recurrence or stage progression. RESULTS: • Additional induction courses of BCG or anticancer drug (mitomycin C or epirubicin) instillations were performed in 119 patients and 24 patients, respectively. The remaining 40 patients did not undergo any adjuvant therapy. • Multivariate analysis showed that a relapsing tumour with a pathologically high risk (defined as tumours with G3 and/or pT1 and/or concomitant carcinoma in situ) was a significant risk factor for subsequent tumour recurrence (P= 0.002; hazard ratio [HR] 2.15). Additional BCG instillation significantly decreased the subsequent tumour recurrence rate (P<0.001; HR 0.41). • Multivariate analysis also showed that a relapsing tumour with a pathologically high risk was also significantly associated with stage progression (P < 0.001; HR 8.05). CONCLUSIONS: • An additional course of BCG instillation might be effective in patients with BCG-relapsing tumours with pathologically intermediate risk. • Nevertheless, some patients with high-risk pathological features developed subsequent stage progression. Such patients should be followed up closely and counselled on the need for aggressive therapeutic options, such as radical cystectomy.

Efficacy of tension-free vaginal tape compared with transobturator tape in the treatment of stress urinary incontinence in women: analysis of learning curve, perioperative changes of voiding function.

BACKGROUND: In this study, by comparing TVT surgery and TOT surgery for stress urinary incontinence in women, the characteristics and learning curves of both operative methods were studied. METHODS: A total of 83 women with stress urinary incontinence treated with tension-free vaginal tape (TVT) (n = 38) or transobturator tape (TOT) (n = 45) at Saiseikai Central Hospital between April 2004 and September 2009 were included. We compare the outcomes and learning curves between TVT surgery and TOT surgery. In statistical analysis, Student's t test, Fisher's exact test, and Mann-Whitney's U test were used. RESULTS: The surgical durations were 37.4 ± 15.7 minutes with TVT surgery and 31.0 ± 8.3 minutes with TOT surgery. A longer period of time was required for TVT surgery (p = 0.025). The residual urine at post-operative day 1 was higher in TVT surgery (25.9 ± 44.2 ml) than in TOT surgery (10.6 ± 19.2 ml) (p = 0.0452). The surgical duration of TVT surgery was shortened after the operator had performed 15 operations (p = 0.019). CONCLUSIONS: In comparison of TVT surgery and TOT surgery, the surgical duration of TVT surgery was longer and the residual urine of TVT surgery was higher at post-operative day 1. Surgical experience could shorten the duration of TVT surgery.

[Assessments of quality of life in women with urinary incontinence using: King's Health Questionnaire and International Consultation on Incontinence Questionnaire-Short Form].

The differences in quality of life (QOL) impairment due to urinary incontinence between elderly and younger women were evaluated using King's Health Questionnaire (KHQ) and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). The subjects were 313 women who consulted the Women's Urinary Incontinence Clinic of Saiseikai Central Hospital between March, 2005 and January, 2008. They were divided into those below or above the cut-off age of 55, 60 or 65 years. The difference in QOL impairment was greatest when the cut-off age was 60 years. Similar comparisons were made by dividing the subjects into those aged 65-74 years and those aged 75 years and above, but no significant difference was noted in the score of any KHQ domain or ICIQ-SF between the two groups. The stress urinary incontinence occurred in younger women and caused the severest impairment. The response rate to KHQ in this study was low especially in the elderly, but that to ICIQ-SF was as high in the elderly as in younger age group. Social activities and lifestyle change around age 60 were considered to be associated with the change of QOL impairment in women with urinary incontinence. The stress urinary incontinence caused the severest impairment. KHQ was often difficult for the elderly to complete, but, ICIQ-SF seemed to be easy.

[A case of double cancer involving the urachus and the bladder].

A 49-year-old male was referred to our hospital with the chief complaint of gross hematuria. We performed cystoscopy, and found a solid tumor at the dome of the bladder. Sagittal magnetic resonance imaging revealed an extravesical tumor at the position of the urachus. Transurethral resection of bladder tumor was performed. A solid tumor at the dome and two papillary tumors at the right lateral region of the bladder were observed. A pathological examination revealed adenocarcinoma from the solid tumor and urothelial carcinoma from the papillary tumors. Under a diagnosis of double cancer, adenocarcinoma of the urachus and urothelial carcinoma of bladder, we performed a total cystectomy, neobladder and total resection of the urachus.

[Primary small cell carcinoma of the ureter: a case report].

An 84-year-old female was referred to our hospital to be examined for left hydronephrosis. Abdominal pelvic computed tomography and ureteroscopy showed an obstructing mass in the left ureter. A biopsy of the mass revealed the presence of small cell carcinoma. A left nephroureterectomy were thus performed.

[A case of intravesical foreign body with a vesical rupture invading the peritoneal cavity: a case report].

A 63-year-old male presented with an intravesical foreign body. We could not remove it by a transurethral operation. We performed open surgery, and found the urinary bladder to be perforated by a foreign body which invaded the peritoneal cavity. To our knowledge, there were 10 similar cases in Japan.

[Clinical study of six cases of pyourachus at our hospital].

We encountered 6 patients with pyourachus (male, 1; female, 5) who ranged in age from 17 to 58 years (mean, 41 years) during the 7 years from 1993 to 1999. Three of them had a history of gynecological surgery, and 2 had a history of appendectomy. Improvement was observed in one patient with conservative therapy alone, but the other 5 patients underwent surgery. Preoperatively, 2 patients underwent drainage, one of them through the umbilicus, and the other through a position on the midline percutaneously. Pathological examination in the 5 patients revealed no evidence of cancer. With reference to postoperative complications, adhesive ileus was recognized in 1 case one year postoperatively but no other complications were noted in the other 5 cases. No evidence of recurrence has been seen in any of these patients to date.