The use of immune checkpoint inhibitors to treat urothelial carcinoma (UC) is increasing rapidly without clear guidance for validated risk stratification. This multicenter retrospective study collected clinicopathological information on 463 patients, and 11 predefined variables were analyzed to develop a multivariate model predicting overall survival (OS). The model was validated using an independent dataset of 292 patients. Patient characteristics and outcomes were well balanced between the discovery and validation cohorts, which had median OS times of 10.2 and 12.5 mo, respectively. The final validated multivariate model was defined by risk scores based on the hazard ratios (HRs) of independent prognostic factors including performance status, site of metastasis, hemoglobin levels, and the neutrophil‐to‐lymphocyte ratio. The median OS times (95% confidence intervals [CIs]) for the low‐, intermediate‐, and high‐risk groups (discovery cohort) were not yet reached (NYR) (NYR–19.1), 6.8 mo (5.8‐8.9), and 2.3 mo (1.2‐2.6), respectively. The HRs (95% CI) for OS in the low‐ and intermediate‐risk groups vs the high‐risk group were 0.07 (0.04‐0.11) and 0.23 (0.15‐0.37), respectively. The objective response rates for in the low‐, intermediate‐, and high‐risk groups were 48.3%, 28.8%, and 10.5%, respectively. These differential outcomes were well reproduced in the validation cohort and in patients who received pembrolizumab after perioperative or first‐line chemotherapy (N = 584). In conclusion, the present study developed and validated a simple prognostic model predicting the oncological outcomes of pembrolizumab‐treated patients with chemoresistant UC. The model provides useful information for external validation, patient counseling, and clinical trial design.
Background/Aim: It is important to delay the emergence of castration-resistant phenotype to improve the prognosis in patients with metastatic castration-sensitive prostate cancer (mCSPC). The objective of this study was to investigate the prognostic impact of time to castration resistance (TTCR) in mCSPC patients. Patients and Methods: This study included 437 consecutive mCSPC patients whose primary androgen deprivation therapy was judged to have failed. Prognostic outcomes in these patients were investigated by dividing them into the following 4 groups of 82, 104, respectively. Results: The mean value of TTCR in the 437 patients was 18.7 months. Of several baseline parameters, significant differences among the 4 groups were noted in the performance status, prostate-specific antigen (PSA) level, lactate dehydrogenase (LDH) level, alkaline phosphatase (ALP) level and Gleason score, all of which favored longer TTCR groups. Furthermore, despite the lack of a significant difference in time from the development of castration-resistant disease to death among the 4 groups, there was a significant difference in overall survival (OS) from diagnosis among these groups, showing prolonged OS proportional to TTCR. Univariate analysis identified the age, PSA level, LDH level, ALP level, Gleason score, visceral metastasis and TTCR as significant predictors of OS, of which only age, ALP level and TTCR were shown to be independently associated with OS on multivariate analysis. Conclusion: mCSPC patients with a longer TTCR are likely to achieve a more favorable OS.Prostate cancer (PC) represents the most commonly diagnosed malignancy and is the second leading cause of cancer-related mortality in men in Western industrialized countries (1). The prognostic outcomes in patients with advanced PC have been improved due to recent advances characterized by the introduction of several novel agents for patients with castration-resistant PC (CRPC), including abiraterone acetate, enzalutamide, and cabazitaxel (2-4). Among patients with advanced PC, however, there remains a proportion with poor prognostic outcomes, such as those newly diagnosed with de novo metastatic diseases (5, 6). Accordingly, it is necessary to conduct a detailed survey focusing on such a patient cohort in order to further improve the survival of patients with advanced PC.Recently, combined treatment with primary androgen deprivation therapy (ADT) and a novel additional agent was demonstrated to significantly improve the prognosis of patients with newly diagnosed metastatic castration-sensitive PC (mCSPC), particularly those with a high-risk disease (7-10). For example, Sweeney et al. conducted the CHAARTED trial comparing the efficacy of ADT alone and ADT plus docetaxel in patients with mCSPC, and showed the significantly longer overall survival (OS) of the combination arm compared to ADT alone (7), while Fizazi et al. reported that the addition of abiraterone acetate and prednisone to ADT significantly improved OS in patients with high-risk mCSPC compared to ADT plus...
Assessment of the De Ritis ratio may provide useful prognostic, but not predictive, information on cabazitaxel therapy in mCRPC patients.
Objective: Unlike for bladder cancer, the impact of regional lymph node dissection for upper tract urothelial carcinoma is unclear. We explored whether patient survival was influenced by systematic regional lymph node dissection, using resection templates according to the main tumor location, during radical nephroureterectomy for upper tract urothelial carcinoma. Methods: The systematic regional lymph node dissection group was defined as cases in which the dissection of nodes and surrounding tissues followed the established template, and the nonsystematic regional lymph node dissection group as cases undergoing limited or no lymph node dissection. We performed radical nephroureterectomy on 98 consecutive patients with various stages of upper tract urothelial carcinoma from May 1994 to September 2014 at our institution. Of these, 77 patients with cTanyN0M0 of upper tract urothelial carcinoma undergoing radical nephroureterectomy were grouped into systematic regional lymph node dissection or non-systematic regional lymph node dissection cohorts according to the extent of dissection, and their outcomes compared. Results: Forty-four patients were categorized as systematic regional lymph node dissection and 33 as non-systematic regional lymph node dissection, including 17 with more limited nodal dissection and 16 with no nodal dissection. Five-year recurrence-free survival and cancer-specific survival were significantly higher in the systematic regional lymph node dissection (93% and 94%, respectively) than in the non-systematic regional lymph node dissection group (75% and 77% recurrence-free survival and cancer-specific survival, respectively). Further, 5-year recurrence-free survival and cancer-specific survival of muscle-invasive upper tract urothelial carcinoma (pT2-4) were significantly higher in the systematic regional lymph node dissection (87% and 91%, respectively) than in the non-systematic regional lymph node dissection group (59% and 62%, respectively) (P = 0.0237 and P = 0.0224). Neither recurrence-free survival nor cancer-specific survival was significantly prolonged by systematic dissection in patients with pTis-1 histology. Conclusions: Systematic regional lymph node dissection during radical nephroureterectomy for cTanyN0M0 upper tract urothelial carcinoma patients has a significantly beneficial impact on survival compared with patients undergoing more limited dissection, especially in the cases involving muscle invasion.
IntroductionThe objective of this study was to evaluate the initial learning curve for robot‐assisted partial nephrectomy (RAPN) using the da Vinci Xi Surgical System (Intuitive Surgical, Sunnyvale, California).MethodsThis study included the initial 65 consecutive patients with small renal tumors who had undergone RAPN at our institution. A single trained surgeon with extensive experience in robot‐assisted radical prostatectomy, but not in laparoscopic partial nephrectomy, performed RAPN for all patients using the da Vinci Xi. The learning curve was analyzed by examining the perioperative outcomes among five groups each consisting of 13 consecutive patients.ResultsIn this series, the median tumor size and R.E.N.A.L. nephrometry score were 23 mm and 7, respectively, and the median console time and warm ischemia time (WIT) were 116 and 15 minutes, respectively. Fifty‐eight patients (89.2%) achieved trifecta outcomes, meaning that the ischemic time was ≤25 minutes, there was a negative surgical margin, and no major postoperative complications occurred. Although there were no significant changes in R.E.N.A.L. nephrometry scores over time, increased surgeon experience was significantly associated with a shorter console time and WIT. Drawing logarithmic approximation curves enabled the achievement of a console time ≤150 minutes and WIT ≤20 minutes at the sixth and fourth procedures, respectively. Furthermore, multivariate analysis identified an independent correlation between surgeon experience with WIT, but not with console time.ConclusionThese findings suggest that regardless of a surgeon's prior experience in laparoscopic partial nephrectomy, an experienced robotic surgeon can perform RAPN using the da Vinci Xi with acceptable perioperative outcomes after a small number of procedures.
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