Comprehensive genomic profiling testing in Japanese castration-resistant prostate cancer patients: results of a single-center retrospective cohort study.

OBJECTIVE: Comprehensive genomic profiling testing using a hybrid-capture next-generation sequencing is commonly used in clinical practice to employ precision medicine in cancer treatment worldwide. In this study, we aimed to analyze the profiles obtained using comprehensive genomic profiling testing that was performed in Japanese castration-resistant prostate cancer patients and to discuss the genetic findings in a real-world setting. METHODS: A total of 60 cases and 57 castration-resistant prostate cancer patients underwent comprehensive genomic profiling testing between 1 January 2021 and 31 December 2022. Four types of comprehensive genomic profiling testing were selected, and clinically significant cancer-specific gene alterations were identified. RESULTS: The median age of patients was 74 years, and the median prostate-specific antigen value at the time of submission was 18.6 ng/ml. Fifty-seven (95%) of 60 cases were metastatic castration-resistant prostate cancers, and 3 cases (5%) were non-metastatic. Among all genetic alterations, androgen-receptor alteration was the most frequently detected in 17 cases (28.3%), followed by 15 cases of TP53 (25.0%), 14 cases of CDK12 (23.3%), 10 cases of phosphatase and tensin homolog (16.7%) and 9 cases of ATM (15.0%) mutations. A total of 13 patients (21.7%) received systemic therapy according to the comprehensive genomic profiling testing results. Overall, the survival rate was significantly greater in the group treated through systemic therapy based on comprehensive genomic profiling testing compared with the group without new therapeutic treatment (P = 0.041). CONCLUSIONS: Comprehensive genomic profiling testing is recommended in castration-resistant prostate cancer patients identified as resistant to standard therapy as this can provide a new therapeutic option.

Clinical characteristics and predictors of long-term postoperative urinary incontinence in patients treated with robot-assisted radical prostatectomy: A propensity-matched analysis.

OBJECTIVES: This study aimed to elucidate the clinical characteristics and predictors of long-term postoperative urinary incontinence (PUI) after robot-assisted radical prostatectomy (RARP). METHODS: This study included patients who underwent RARP at our institution and were stratified into PUI (≥1 pad/day) and continence (0 pad/day) groups at 60 months after RARP. A propensity score-matched analysis with multiple preoperative urinary status (Expanded Prostate Cancer Index Composite urinary subdomains, total International Prostate Symptom Score (IPSS), and IPSS-quality of life scores) was performed to match preoperative urinary status in these groups. Serial changes in urinary status and treatment satisfaction preoperatively and until 60 months after RARP were compared, and predictors of long-term PUI were assessed using multivariate logistic regression analysis. RESULTS: A total of 228 patients were included in the PUI and continence groups (114 patients each). Although no significant difference in preoperative urinary status was observed between the two groups, the postoperative urinary status significantly worsened overall in the PUI group than in the continence group. Treatment satisfaction was also significantly lower in the PUI group than in the continence group from 12 to 60 months postoperatively. Multivariate logistic regression analysis revealed that age (≥70 years) and biochemical recurrence (BCR) were significant predictors of the long-term PUI group (p < 0.05). CONCLUSIONS: Patients with long-term PUI had poor overall postoperative urinary status and lower treatment satisfaction than the continence group. Considering the age and risk of BCR is important for predicting long-term PUI when performing RARP.

Preoperative high serum total testosterone levels predict preserved postoperative sexual function in patients after nerve-sparing robot-assisted radical prostatectomy.

OBJECTIVE: To assess the association among preoperative total testosterone levels, postoperative sexual function, and prognosis after robot-assisted radical prostatectomy. METHODS: Patients who underwent robot-assisted radical prostatectomy in our institution were included in the study. Based on preoperative total testosterone levels, they were divided into low (<3.0 ng/mL) and high (≥3.0 ng/mL) total testosterone groups. Sexual function was evaluated using the International Index of Erectile Function scores, Expanded Prostate Cancer Index Composite scores, and the potency rate from preoperatively to 12 months after surgery. Oncological outcomes were evaluated based on biochemical recurrence. RESULTS: Out of 233 patients included, no significant difference in sexual function was found between the high (n = 183) and the low (n = 50) total testosterone groups at any point before or after surgery. However, in nerve-sparing cases, preservation in postoperative sexual function was observed only in the high total testosterone group (International Index of Erectile Function scores and Expanded Prostate Cancer Index Composite sexual function scores, at any point after surgery, p < 0.05; potency rate, at 3, 6, and 12 months after surgery; p < 0.05). Additionally, the high total testosterone group showed better biochemical recurrence-free survival than the low total testosterone group (p = 0.008). CONCLUSIONS: In the high total testosterone group, preservation in sexual function was observed after the nerve-sparing procedure, while the biochemical recurrence rate was low. Therefore, patients with high levels of total testosterone may be advised to consider nerve-sparing interventions.

Risk classification system using the detailed positive surgical margin status for predicting biochemical recurrence after robot-assisted radical prostatectomy.

AIM: This study aimed to evaluate the risk classification system using the detailed positive surgical margin (PSM) status to predict biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP). METHODS: We retrospectively analyzed 427 patients who underwent RARP between January 2016 and March 2020. We investigated risk factors for BCR using univariate and multivariate Cox proportional hazard regression models. The biochemical recurrence-free survival (BRFS) rate was assessed using the Kaplan-Meier method. RESULTS: The median follow-up period was 43.4 months and 99 patients developed BCR. In the multivariate analysis, maximum PSM length > 5.0 mm and the International Society of Urological Pathology grade group (ISUP GG) at the PSM ≥3 were predictive factors for BCR in patients with a PSM. In the multivariate analysis, these factors were also independent predictive factors in the overall study population, including patients without a PSM. We classified the patients into four groups using these factors and found that the 1-year BRFS rates in the negative surgical margin (NSM) group, low-risk group (PSM and neither factor), intermediate-risk group (either factor), and high-risk group (both factors) were 94.9%, 94.5%, 83.1%, and 52.9%, respectively. The low-risk group showed similar BRFS to the NSM group (p = 0.985), while the high-risk group had significantly worse BRFS than the other groups (p < 0.001). CONCLUSION: Maximum PSM length > 5.0 mm and ISUP GG at the PSM ≥3 were independent predictive factors for BCR after RARP. Risk classification for BCR using these factors is considered to be useful and might help urologists decide on additional treatment after RARP.

Prognostic Impact of the Modified 5-Item Frailty Index After Radical Nephroureterectomy in Patients With Upper Tract Urothelial Carcinoma: A Multicenter Retrospective Study.

INTRODUCTION: The modified 5-item frailty index can be used to evaluate frailty using 5 routinely encountered clinical variables. This study aimed to assess the impact of the modified 5-item frailty index in patients who underwent radical nephroureterectomy for upper tract urothelial carcinoma. PATIENTS AND METHODS: In this multicenter retrospective study, we calculated the modified 5-item frailty index scores of patients who underwent radical nephroureterectomy for upper tract urothelial carcinoma between 2010 and 2022. Patients were categorized into the high (≥2) and low (≤1) modified 5-item frailty index score groups. To assess the prognostic influence of the preoperative modified 5-item frailty index, we conducted Cox proportional regression analyses concerning progression-free, overall, and cancer-specific survival. RESULTS: Of 434 patients, 82, and 352 were classified into the high and low modified 5-item frailty index score groups, respectively. The high modified 5-item frailty index score group had significantly higher rates of severe surgical complications (P = .038) and ≥30 days of hospitalization (P = .049) and significantly worse progression-free (P = .012) and overall survival (P = .002) than the low modified 5-item frailty index score group. The multivariable Cox proportional hazard analysis revealed that a high modified 5-item frailty index score was independently associated with poor progression-free (P = .044), overall (P = .017), and cancer-specific survival (P = .005). CONCLUSION: The modified 5-item frailty index emerged as a significant predictive indicator of severe surgical complications and postoperative survival outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.

Enzalutamide versus Abiraterone Plus Prednisolone for Nonmetastatic Castration-Resistant Prostate Cancer: A Sub-Analysis from the ENABLE Study for PCa.

Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) can improve the survival of patients with castration-resistant prostate cancer (CRPC). However, the agent that is more effective against nonmetastatic CRPC remains unclear. To evaluate the agent that can be used as the first-line treatment for CRPC, an investigator-initiated, multicenter, randomized controlled trial (ENABLE Study for PCa) including both metastatic and nonmetastatic CRPC was conducted in Japan. The prostate-specific antigen (PSA) response rate, overall survival, some essential survival endpoints, and safety of patients with nonmetastatic CRPC were also analyzed. In this subanalysis, 15 and 26 patients in the ENZ and ABI arms, respectively, presented with nonmetastatic CRPC. There was no significant difference in terms of the PSA response rate between the ENZ and ABI arms (80% and 64%, respectively; p = 0.3048). The overall survival did not significantly differ between the two arms (HR: 0.68; 95% CI: 0.22-2.14, p = 0.5260). No significant differences were observed in terms of radiographic progression-free survival and cancer-specific survival between the ENZ and ABI arms (HR: 0.81; 95% CI: 0.35-1.84; p = 0.6056 and HR: 0.72; 95% CI: 0.19-2.73; p = 0.6443, respectively). Only four and six patients in the ENZ and ABI arms, respectively, had ≥grade 3 adverse events. ABI and ENZ had similar efficacy and safety profiles in patients with nonmetastatic CRPC.

Comparison of surgical outcomes and split renal function between laparoscopic and robot-assisted partial nephrectomy: a propensity score-matched analysis.

PURPOSE: The objective of this study was to compare perioperative outcomes and total and split renal function between laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN). Predictive risk factors of preservation of operated renal function were also assessed. METHODS: We retrospectively analyzed 173 patients who underwent LPN (n = 84) or RAPN (n = 89) between 2010 and 2020. After propensity score matching (1:1), perioperative outcomes and total and split renal function were assessed. Logistic regression analysis was used to evaluate predictive risk factors of preservation of operated renal function. Trifecta criteria were defined as negative surgical margins, warm ischemia time (WIT) < 25 min, and no complications more than Clavien-Dindo grade II within 4 weeks after surgery. Split renal function was evaluated by mercaptoacetyltriglycine renal scan. RESULTS: After propensity score matching, 42 patients were allocated to each group. RAPN was associated with significantly shorter WIT (RAPN vs LPN: 12 vs 22 min; p < 0.0001) and higher trifecta achievement rate (93.3 vs 64.2%; p < 0.0001). Other perioperative outcomes and total and split renal function were not significantly different between LPN and RAPN. The R.E.N.A.L. nephrometry score (RNS) was a predictive risk factor of preservation of operated renal function in the multivariable logistic regression analysis (odds ratio 1.68, 95% confidence interval 1.29-2.20, p < 0.0001). CONCLUSIONS: RAPN improved WIT and trifecta achievement rate, but it did not improve the preservation of operated renal function, for which RNS was found to be a strong predictive risk factor.

Successful treatment of recurrent small cell carcinoma of urinary bladder with pembrolizumab.

INTRODUCTION: Small cell carcinoma of urinary bladder is rare and has an aggressive malignant behavior and poor prognosis. Advanced bladder cancers are treated with immune checkpoint inhibitors, however, its efficacy for small cell carcinoma of urinary bladder is unclear. CASE PRESENTATION: A 54-year-old female, diagnosed with clinical stage T2N0M0 small cell carcinoma of urinary bladder, underwent radical cystectomy after three cycles of etoposide-cisplatin neoadjuvant chemotherapy. Despite the fact that pathological examination revealed no residual carcinoma in bladder in her cystectomy specimen, local recurrence of a 60-mm mass detected in the follow-up investigation 7.5 months later. This was completely treated by pembrolizumab without any adverse effects. Immunohistochemical staining revealed that the tumor had no programmed death ligand 1 expression but it showed CD8-positive T-lymphocyte infiltration into the tumor. CONCLUSION: Immune checkpoint inhibitors might have curative potentials for treatment of small cell carcinoma of urinary bladder.

Refractory fistula of bladder repaired with transurethral cystoscopic injection of N-butyl-2-cyanoacrylate.

INTRODUCTION: Refractory fistulas of the bladder are not rare, but they can rarely be closed naturally. Bladder fistulas can be treated in various ways. We report the case of an old woman who had a refractory fistula of the bladder that was able to be repaired with transurethral cystoscopic injection of N-butyl-2-cyanoacrylate. CASE PRESENTATION: For decades after being treated for cervical cancer in 1970s, the woman frequently suffered from fevers. A computed tomography scan showed pelvic abscess at the left side of her bladder, and cystography showed urine leakage at the wall. Thus, we diagnosed her with a pelvic abscess due to a bladder fistula after radiation. Then, we treated her with drainage, antibiotic agents, and N-butyl-2-cyanoacrylate. After that, she no longer had fevers, and cystography showed no leakage of urine. CONCLUSION: This result indicates transurethral cystoscopic injection of N-butyl-2-cyanoacrylate may treat bladder fistulas safely, minimally invasively, and quickly.

Pneumatosis cystoides intestinalis linked to sunitinib treatment for renal cell carcinoma.

INTRODUCTION: Pneumatosis cystoides intestinalis is a rare condition characterized by air-filled cysts within intestinal walls. It can be caused by various factors. We report a case of pneumatosis cystoides intestinalis linked to sunitinib treatment for renal cell carcinoma. CASE PRESENTATION: A 67-year-old female with advanced renal cell carcinoma who had been treated with sunitinib visited our hospital complaining of abdominal pain. Computed tomography scans showed diffuse air-filled cystic formation of intestine. We treated with conservative therapy, and she recovered. However, although air-filled cysts disappeared in the images, intraoperative findings in the resection of a recurrent paracaval lymph node showed a thinning of the intestine. CONCLUSION: It is necessary to consider pneumatosis cystoides intestinalis when a patient using a tyrosine kinase inhibitor complains of abdominal symptoms. It should also be noted that the effect of pneumatosis cystoides intestinalis may remain even if pneumatosis disappears from the image on tomography scans.

Case of renal mucinous tubular and spindle cell carcinoma with high nuclear grade.

INTRODUCTION: Renal mucinous tubular and spindle cell carcinoma is a rare subtype of renal cell carcinoma newly added to the World Health Organization classification in 2004. Although it has been considered as a tumor with good prognosis, aggressive cases have recently been reported. CASE PRESENTATION: A 52-year-old man was diagnosed as having left renal cell carcinoma. Open radical left nephrectomy and left-sided pelvic lymph nodes dissection were performed. Pathological diagnosis revealed a renal mucinous tubular and spindle cell carcinoma with high nuclear grade and extra-regional lymph nodes metastasis classified as pT3aN0M1. After nephrectomy, metastasis at second lumbar vertebra and lymph nodes recurrence were occurred. CONCLUSION: This tumor with high nuclear grade may be potentially aggressive and carries a poor prognosis.