Patient-reported outcomes following neoadjuvant endocrine therapy, external beam radiation, and adjuvant continuous/intermittent endocrine therapy for locally advanced prostate cancer: A randomized phase III trial.

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.

Oncological outcomes for patients with locally advanced prostate cancer treated with neoadjuvant endocrine and external-beam radiation therapy followed by adjuvant continuous/intermittent endocrine therapy in an open-label, randomized, phase 3 trial.

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.

The feasibility and effectiveness of robot-assisted radical cystectomy after neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer.

OBJECTIVES: The aim of this study was to compare 29 muscle-invasive bladder cancer patients who received neoadjuvant chemotherapy (NAC) followed by immediate robot-assisted radical cystectomy (RARC) with those who underwent minimum-incision endoscopic RC (MIE-RC). METHODS: We retrospectively reviewed the charts of 430 consecutive patients who underwent RC and bilateral pelvic node dissection (PLND) between May 1994 and July 2016. Our study focused on patients with MIBC who had histologically confirmed stage T2-T4aN0M0 urothelial carcinoma of the bladder and received NAC prior to surgery. Accordingly, 225 patients were included in this analysis, of whom, 29 underwent RARC (RARC group) and 196 underwent MIE-RC (MIE-RC group). The primary endpoints in this study were the positive surgical margin (PSM) rate and lymph node (LN) count. RESULTS: In the RARC group, 20 patients underwent RARC with intracorporeal urinary diversion and nine patients underwent RARC with extracorporeal urinary diversion. The median surgical duration for RC and bilateral PLND was 125 min in the RARC group and 98 min in the MIE-RC group (P < 0.001). The rate of PSM was 0% in the RARC group and 0.5% in the MIE-RC group. The median LN counts were 15 in the RARC group and 18 in the MIE-RC group. No intra-operative complication or mortality was associated with RARC or MIE-RP. All complications were grade 2 according to the Clavien-Dindo classification. CONCLUSIONS: Our initial experience with NAC followed by RARC appears to be favorable, with acceptable operative and perioperative clinical outcomes when compared with those of MIE-RC.

Feasibility of classical secondary hormonal therapies prior to docetaxel therapy in Japanese patients with castration-resistant prostate cancer: Multicenter retrospective study.

BACKGROUND: We retrospectively analyzed castration-resistant prostate cancer (CRPC) patients treated with secondary hormonal therapies (SHTs) prior to docetaxel therapy. METHODS: The cases of 73 CRPC patients who underwent docetaxel therapy in 2005-2011 at four hospitals in Ibaraki, Japan were analyzed. We determined the cause-specific survival (CSS) from the start of docetaxel therapy and the time point of CRPC diagnosis, and we compared the CSS achieved with/without prior classical SHTs, which were defined as low-dose steroid and estramustine phosphate. RESULTS: Of the 73 enrolled patients, 26 underwent docetaxel therapy (DOC group), and 47 underwent SHTs (SHTs-DOC group) as the initial treatment for CRPC. In the docetaxel therapy, the rate of prostate-specific antigen responses were higher in the DOC group compared with the SHTs-DOC group (76.9% vs. 44.7%, P = 0.0066). The median CSS from the docetaxel therapy initiation was not significant but longer in the DOC group than in the SHTs-DOC group (23.4 months vs. 16.6 months, P = 0.0969). However, the median CSS from the time of CRPC diagnosis did not significantly differ between the DOC and SHTs-DOC groups (23.4 months vs. 24.7 months, P = 0.9233). In a univariate analysis, pain and visceral metastasis appeared to be risk factors for the CSS in the SHTs-DOC group. The patients with pain and/or visceral metastasis had significantly poorer survival than those without these factors in the SHTs-DOC group (31.5 months vs. 16.8 months, P = 0.0053). CONCLUSION: The induction of SHTs prior to docetaxel therapy is an acceptable treatment option with some survival benefits for CRPC patients without pain and visceral metastases.

Quality of gastric cancer care in designated cancer care hospitals in Japan.

OBJECTIVE: To develop a set of process-of-care quality indicators (QIs) that would cover a wide range of gastric cancer care modalities and to examine the current state of the quality of care provided by designated cancer care hospitals in Japan. DESIGN: A retrospective medical record review. SETTING: Eighteen designated cancer care hospitals throughout Japan. PARTICIPANTS: A total of 1685 patients diagnosed with gastric cancer in 2007. MAIN OUTCOME MEASURES: Provision of care to eligible patients as described in the 29 QIs, which were developed using an adaptation of the RAND/UCLA (University of California, Los Angeles) appropriateness method by a panel of nationally recognized experts in Japan. RESULTS: Overall, the patients received 68.3% of the care processes recommended by the QIs. While 'deep venous thrombosis prophylaxis before major surgery' was performed for 99% of the cases, 'documentation before endoscopic resection' was completed for only 12% of the cases. The chemotherapy care was less likely to meet the QI standards (61%) than pre-therapeutic care (76%), surgical treatment (66%) and endoscopic resection (71%; overall difference: P < 0.001). A comparison based on the types of care showed that documentation and patient explanation were performed less frequently (60 and 53%, respectively) than were diagnostic and therapeutic processes as recommended in the QIs (85%; overall P < 0.001). CONCLUSIONS: Although many required care processes were provided, some areas with room for improvement were revealed, especially with respect to chemotherapy, documentation and patient explanation. Continuous efforts to improve the quality and develop a system to monitor this progress would be beneficial in Japan.

The effects of chlormadinone acetate on lower urinary tract symptoms and erectile functions of patients with benign prostatic hyperplasia: a prospective multicenter clinical study.

Purpose. To evaluate the effects of chlormadinone acetate (CMA), progesterone-derived antiandrogen, on lower urinary tract symptoms (LUTS) and erectile functions of benign prostatic hyperplasia (BPH). Methods. A multicenter, single-cohort prospective study was conducted. A total of 114 patients received CMA for 16 weeks. The endpoints were changes in International Prostate Symptom Scores (IPSS), IPSS-QOL, International Index of Erectile Function-5, Q max prostate volume, and residual urine volume. Results. Significant improvements were observed in IPSS from week 8 to week 48 (32 weeks after treatment). IPSS-QOL improvements were also significant from week 8 to week 48. Q max increased to a maximum at Week 16 and remained elevated throughout the study. Moreover, a decrease of 25% in prostate volume was observed at Week 16. IPSS, QOL, and Qmax changes during the study were not different between the previously treated and untreated patients. IPSS storage subscore changes differed between the age groups. Few severe adverse reactions were observed, except for erectile dysfunction. Conclusions. CMA rapidly and significantly reduced prostate volume and improved voiding and storage symptoms and QOL. Our results suggest that CMA is safe and beneficial, especially for elderly patients with LUTS associated with BPH.

Usefulness of urinary NMP22 to detect tumor recurrence of superficial bladder cancer after transurethral resection.

BACKGROUND: In a prospective study we compared the usefulness of urinary nuclear matrix protein 22 (NMP22) with that of urine cytology and other urinary markers in the monitoring of superficial bladder cancer after transurethral resection (TURBT). METHODS: The subjects were 156 patients, comprising 99 patients with superficial bladder cancer in whom TURBT was planned (untreated group) and 57 patients without tumors in the bladder who had been followed up after TURBT (follow-up group). RESULTS: Among the 156 patients, who were monitored for 11-26 months (median, 21 months), recurrence was observed in 51 patients (33.0%). At the time of recurrence, the sensitivities of NMP22, basic fetoprotein (BFP), and bladder tumor antigen (BTA) tests, and urine cytology were 18.6%, 23.3%, 9.3%, and 7.0%, respectively. The factors affecting the sensitivity of NMP22 were tumor size and urinary WBC. The size of recurrent tumors was significantly smaller (P<0.05) than that of the initial tumors. Based on receiver operating characteristic (ROC) curves calculated from the data of patients with recurrence, the ideal cutoff values at recurrence were recommended to be 5.0 U/ml for NMP22 and 6.0 ng/ml for BFP. Using these cutoff values, the sensitivities of NMP22 and BFP were 48.8% and 44.2%, respectively. CONCLUSIONS: Because the size of recurrent bladder tumors is usually smaller than that of the initial tumors, the cutoff values of urinary markers should be reduced to detect these tumors. We recommend 5.0 U/ml as a cutoff value of NMP22 for detection of recurrence of bladder tumor.

Immunological protection induced by bacillus Calmette-Guérin treatment in a murine bladder tumor model.

BACKGROUND: It has been previously reported that MBT-2 tumor growth is completely inhibited when mice are inoculated with bacillus Calmette-Guérin (BCG). In this study it was examined whether or not vaccination with a mixture of BCG and MBT-2 cells also induces immunological protection against murine bladder tumors. METHODS: Seven hundred thousand MBT-2 cells and 1 mg of BCG (Tokyo 172 strain) per mouse were injected subcutaneously into female C3H/HeN mice. Four and eight weeks after vaccination with this mixture, animals were reinoculated with MBT-2 cells alone or MBT-2 cells cocultured with BCG. RESULTS: Animals vaccinated with a mixture of BCG and MBT-2 cells showed MBT-2 tumor growth but completely rejected the MBT-2 cells cocultured with BCG. MBT-2 cells cocultured with BCG developed into tumors when they were inoculated into the control animals. Splenocytes prepared from vaccinated animals showed specific cytocidal activity against MBT-2 cells precultured with BCG. CONCLUSIONS: The results suggest that a mixture of BCG and MBT-2 cells induces antitumor immunological protection against BCG- or MBT-2-associated antigens presented on MBT-2 cells precultured with BCG.