Treatment Outcomes of Second-Line Systemic Therapy for Neuroendocrine Prostate Cancer: A Report of Four Cases.

Neuroendocrine prostate cancer (NEPC) is a histological variant of prostate cancer and is characterized by aggressiveness and poor clinical outcomes. NEPC usually develops as a mechanism of treatment resistance in patients receiving hormone therapy for advanced prostate cancer. NEPC is sensitive to primary platinum-based chemotherapy, and has a short response duration. Second-line therapy is required in many cases, but clinical data on subsequent treatment after progression to first-line chemotherapy is limited. Here we report our experience of four cases of NEPC treated with second-line chemotherapy. Progression-free and overall survival rates were very low in three of the patients. One patient received multidisciplinary therapy using systemic and local chemotherapy and radiation therapy and survived for 24 months after initiation of second-line chemotherapy. Multidisciplinary therapy with chemotherapy and radiation is a promising option for improving the survival of patients with NEPC.

Differential impact of proton pump inhibitor on survival outcomes of patients with advanced urothelial carcinoma treated with chemotherapy versus pembrolizumab.

OBJECTIVES: We clarified the effect of concomitant proton pump inhibitor use on oncological outcomes in patients with advanced urothelial carcinoma treated either with chemotherapy or immune checkpoint inhibitor. METHODS: We retrospectively reviewed patients with advanced urothelial carcinoma who received paclitaxel-gemcitabine therapy or pembrolizumab after platinum-based chemotherapy. The patients were divided into four groups based on the treatment regimen and the concomitant use of proton pump inhibitor. We compared survival outcomes between the groups and determined which factors predicted overall survival. RESULTS: Among the 60 and 75 patients treated with paclitaxel-gemcitabine and pembrolizumab, 15 and 29 used a concomitant proton pump inhibitor. Progression-free and overall survival was significantly shorter in patients who were administered pembrolizumab with concomitant proton pump inhibitor compared to those without. The use of a concomitant proton pump inhibitor had no effect on survival outcomes in patients who received paclitaxel-gemcitabine therapy. Furthermore, progression-free and overall survival were significantly shorter in patients treated with paclitaxel-gemcitabine therapy compared to those treated with pembrolizumab among patients without concomitant proton pump inhibitor. In contrast, there was no difference in survival outcomes between the two regimens among patients with concomitant proton pump inhibitor. Concomitant proton pump inhibitor use was associated with poor overall survival only in patients treated with pembrolizumab. CONCLUSION: The use of a concomitant proton pump inhibitor use had no impact on oncological outcomes in patients with advanced urothelial carcinoma treated with paclitaxel-gemcitabine therapy, different from those treated with pembrolizumab.

[Clinical Statistics From 2017 to 2019 in the Department of Urology, Hospital of the University of the Occupational and Environmental Health, Japan].

We introduced the da Vinci Xi surgical system (Intuitive Surgical G.K. CA) in January 2018, and here we report clinical statistics on outpatients, inpatients, and surgical procedures for the 3-year period from January 2017 to December 2019. The number of new outpatients since 2017 has remained almost unchanged at 1,406, 1,530, and 1,494 per year. There was an increasing trend in the number of inpatients, from 862 to 1,021 to 1,239. The main diseases of the inpatients over the 3-year period were bladder cancer in 676 (21.7%), renal cancer in 374 (12.0%), prostate cancer in 268 (8.6%), and urolithiasis in 263 (8.4%). The total number of surgeries in the three years was 1,931. The numbers of transurethral surgeries and laparoscopic surgeries, including robotic surgeries, were 1,063 (55.0%) and 396 (20.5%), respectively. The numbers of inpatients and surgery have been increasing year by year. Medical resources are limited and need to be distributed more efficiently.

Combination therapy with paclitaxel and gemcitabine after platinum-based chemotherapy in patients with advanced urothelial cancer.

OBJECTIVES: To evaluate the efficacy and tolerability of paclitaxel and gemcitabine therapy after platinum-based chemotherapy for patients with advanced urothelial carcinoma. METHODS: Consecutive patients with advanced urothelial carcinoma who received paclitaxel and gemcitabine therapy from December 2003 to March 2018 were retrospectively reviewed. The objective response for paclitaxel and gemcitabine therapy, progression-free survival and overall survival, and adverse events were evaluated. The reduction rate among each metastatic site and the associations between the clinical parameters and overall survival or progression-free survival were also assessed. RESULTS: We enrolled 58 patients. Complete and partial responses were observed in two (3.4%) and 15 patients (26%), respectively. The median progression-free survival and overall survival were 4.3 months (95% confidence interval 2.9-5.2) and 11.5 months (95% confidence interval 7.7-14.8), respectively. The objective response rates of primary site and metastases in lymph nodes, lung, bone, and liver were 6.0%, 37%, 23%, 0%, and 22%, respectively. Poor performance status (≥1), prior use of gemcitabine and the number of metastatic sites (≥2) were significantly associated with poor overall survival. Although three patients discontinued the treatment because of adverse events, there was no therapy-related death. CONCLUSIONS: Paclitaxel and gemcitabine therapy seems to be a valid option as a subsequent treatment after platinum-based chemotherapy for urothelial carcinoma, especially in patients with favorable performance status and no prior use of gemcitabine.

Oncological Outcome After Radical Prostatectomy without Pelvic Lymph Node Dissection for Localized Prostate Cancer: Follow-up Results in a Single Institution.

The oncological benefit of pelvic lymph node dissection (PLND) is still debatable because data on clinical outcomes of radical prostatectomy (RP) without PLND are lacking. In this study, we reported oncological outcome in consecutive 146 patients who underwent RP without PLND. Although 27% of our patients developed biochemical recurrence, the estimated 5-year overall survival rates were 100%, 96.3%, and 95.7% in the low-, intermediate-, and high-risk groups, respectively. These data in our patients were not inferior to those in previous reports that investigated the survivals in patients who received PLND during RP. The therapeutic significance of PLND should be re-evaluated.

Premature Mortality Due to Malignancies of the Kidney and Bladder in Japan, 1980-2010.

BACKGROUND: In the present study, we examined the trends of premature mortality due to kidney and bladder cancers among the Japanese population from 1980 through 2010. METHODS: Mortality data were obtained from the World Health Organization mortality database. Years of life lost (YLL) was estimated using Japanese life tables. Average lifespan shortened (ALSS) was calculated and defined as the ratio of years of life lost relative to the expected lifespan. RESULTS: Over the study period, the age-standardized rates to the World Standard Population for deaths from kidney and bladder cancers were stable. The average years of life lost (AYLL) measure shows decreases of about 4 and 6 years of life for kidney cancer in men and women, respectively, and decreases of about 2 years of life for bladder cancer in both sexes. The ALSS shows that patients with kidney cancer lost 21.0% and 24.7% of their lifespan among men and women in 1980, whereas respective losses were 15.3% and 15.8% in 2010. Also, patients with bladder cancer on average lost 13.5% in men and 14.2% in women in 1980 and 10.8% in men and 11.1% in women in 2010. CONCLUSIONS: Our study shows favorable trends in premature mortality for kidney and bladder cancers in Japan over a 30-year period; however, patients with bladder cancer on average lost a smaller proportion of their lifespan compared to those with kidney cancer. The development of a novel ALSS measure is convenient in examination of the burden of premature mortality over time.

Reconsideration on Clinical Benefit of Pelvic Lymph Node Dissection during Radical Prostatectomy for Clinically Localized Prostate Cancer.

We conducted a review of the literature to identify the clinical benefits of pelvic lymph node dissection (PLND) during radical prostatectomy for clinically localized prostate cancer. The most recent guidelines recommend PLND, particularly extended PLND, during radical prostatectomy for localized prostate cancer. PLND is undoubtedly the most accurate method for nodal staging, and most patients, particularly those with high-risk cancer, are likely to undergo PLND during radical prostatectomy. Although many retrospective studies have assessed oncologic outcomes after PLND, its therapeutic benefit remains controversial. Patients with positive node(s) often have other more common unfavorable prognostic factors, such as seminal vesicle invasion, extra-prostatic extension, and positive surgical margins. Oncologic outcomes in patients who have not undergone PLND and those who have undergone PLND are almost identical. If an effective standard adjuvant therapy after prostatectomy is defined, the nodal status may be important and valuable. However, adjuvant treatment strategies for patients with a positive node have not been identified thus far. Therefore, determining the nodal status at surgery may not provide therapeutic benefit. PLND requires additional surgical time and is associated with several complications. Therefore, the indication for PLND should be considered carefully until well-designed prospective randomized trials establish high-quality clinical evidence.

Efficacy and Tolerability of Bacillus Calmette-Guérin Therapy as the First-Line Therapy for Upper Urinary Tract Carcinoma In Situ.

There are few data on Bacillus Calmette-Guérin (BCG) therapy for upper urinary tract carcinoma in situ (UUT CIS). We retrospectively evaluated the efficacy and tolerability of BCG therapy for 41 patients [52 renal units(RUs)] with UUT CIS. Of 52 RUs, complete response was achieved in 47 (90%). The 5-year recurrence-, progression-free survival rates were 60.2% and 74.2%, respectively. Adverse events were observed in 31 (76%) patients, but most of them were mild. The scheduled instillations were completed in 31 (74%) of 42 patients. Our results demonstrated that BCG therapy for UUT CIS was satisfactory with high efficacy and tolerability.

Clinical Significance of Squamous Differentiation in Urothelial Carcinoma of the Bladder.

The prognostic value of squamous differentiation (SD) in urothelial carcinoma (UC) of the bladder is unclear. The aim of this study was to identify the clinical significance of SD in UC in terms of oncological outcomes in patients undergoing radical cystectomy (RC). We evaluated consecutive patients with muscle-invasive bladder cancer (MIBC; clinical T2-4aN0M0) treated with RC at our institution from March 2003 to March 2017. We enrolled 20 and 81 patients with UC with SD (UCSD) and pure UC, respectively. Postoperative survival outcomes were compared between the patients with UCSD and pure UC using the Kaplan-Meier method. Pre- and postcystectomy factors that influenced the overall survival (OS) and recurrence-free survival (RFS) were investigated in these patients. Multivariate Cox regression models were used to identify the predictors of OS and RFS. With a median follow-up time of 31 months, the 5-year OS rate of the UCSD and pure UC groups was 41.1% and 69.7% ( P = .002) and the 5-year RFS rate was 51.8% and 59.5% ( P = .027), respectively. The shape of the Kaplan-Meier curves for UCSD suggested a more rapid course of the disease within the first 2 years than observed in pure UC. Multivariate analyses suggested that SD in UC was significantly associated with OS (hazard ratio [HR]: 4.22; 95% confidence interval [CI]: 1.20-14.8; P = .024) and close to significance for a lower RFS (HR: 2.13, 95% CI: 0.74-6.15, P = .064). Our results indicate that SD may be an independent predictor of OS and RFS in UC of MIBC in patients undergoing RC.

The Omission of Upfront Treatment Intensification Does Not Adversely Affect Oncological Outcomes in a Subset of Castration-Highly Sensitive Metastatic Prostate Cancer.

BACKGROUND/AIM: In patients with metastatic castration-sensitive prostate cancer (mCSPC), upfront treatment intensification with the addition of new hormonal agents and/or docetaxel to androgen deprivation therapy (ADT) is recommended. However, this modality is potentially excessive in a subset of these patients. This study aimed to identify patients who may be eligible to omit upfront treatment intensification. PATIENTS AND METHODS: Patients with mCSPC who underwent ADT were enrolled. The association between undetectable prostate-specific antigen (PSA) (<0.2 ng/ml) after ADT initiation and overall or castration-resistance-free survival was evaluated. RESULTS: Ninety-seven out of the 242 enrolled patients had low-risk and/or low-volume cancer and were further analyzed. Of these, 45 (46.4%) patients achieved undetectable PSA. The median follow-up period after ADT initiation was 70 months. The median overall survival among patients with undetectable PSA was quite long, reaching 226 months and significantly longer than that among patients with detectable PSA [71 months, hazard ratio (HR)=0.27, 95% confidence interval (CI)=0.15-0.49, p<0.001]. Time to development of castration-resistance was also long and significantly longer in the undetectable PSA group than that in the detectable PSA group (median: 124 vs. 17 months, HR=0.20, 95% CI=0.12-0.34, p<0.001). CONCLUSION: Patients with low-risk and/or low-volume mCSPC showed long-term survival when undetectable PSA was achieved during conventional ADT. In these patients, skipping upfront treatment intensification does not seem to negatively impact survival.