Radiographic Progression at Castration-Resistant Prostate Cancer Diagnosis: A Prognostic Indicator of Metastatic Hormone-Sensitive Prostate Cancer.

BACKGROUND: The critical role of radiographic assessment at the time of castration-resistant prostate cancer (CRPC) diagnosis is underscored by this study. We performed a retrospective analysis of radiographic changes in metastasis from the time of diagnosis of metastatic hormone-sensitive prostate cancer (mHSPC) to CRPC diagnosis. We also explored its impact on prognosis post-CRPC. MATERIALS AND METHODS: We retrospectively analyzed 98 men who underwent radiographic examinations (bone scans and computed tomography [CT]) at the time of CRPC diagnosis. When radiographic studies demonstrated progression at CRPC diagnosis, patients were assigned to the radiographic progressive disease (rPD) group. The remaining patients were placed in the "non-rPD" group. The overall survival (OS) post-CRPC was compared between the 2 groups. RESULTS: The median OS post-CRPC was significantly shorter in the rPD group (n = 50) compared to the non-rPD group (n = 48) (32 months vs. not reached, P = .0124). Multivariate analysis showed that radiographic progression and shorter time to CRPC were associated with a shorter OS post-CRPC (hazard ratio [HR] = 3.14; 95% confidence interval [CI], 1.21-8.12, P = .019). CONCLUSION: Radiographic progression at the point of CRPC diagnosis independently predicts a shorter OS post-CRPC in patients with mHSPC. Therefore, assessing radiographic changes at the time of CRPC diagnosis could be instrumental in managing CRPC in patients with mHSPC.

Association between comorbidities and survival in patients with metastatic urothelial carcinoma treated with pembrolizumab.

BACKGROUND: This study aims to investigate the relationship between comorbidities and survival in patients with mUC treated with pembrolizumab as a second-line treatment. METHODS: From February 2018 to October 2021, we analyzed the data of 185 consecutive patients with metastatic UC who received pembrolizumab as second-line therapy at The Jikei University Hospital and five affiliated hospitals. We used the Charlson Comorbidity Index (CCI) to assess the comorbidities. The outcomes of interest were progression-free survival (PFS) and overall survival (OS). To compare the survival differences, inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and the IPTW-adjusted Cox regression hazards model were used. RESULTS: After IPTW adjustment, patient characteristics were well-balanced between patients with high CCI and those with low CCI. The IPTW-adjusted Kaplan-Meier curves of PFS and OS based on CCI revealed that the patients with high CCI (2 or more) had a shorter PFS (median, 1.6 vs. 2.8 months) and a shorter OS (median, 12.4 vs. 18.8 months) (0-1). Similarly, in the IPTW-adjusted Cox regression hazards model, patients with high CCI had significantly shorter PFS [HR, 1.84 (95% CI 1.26-2.68; p = 0.002)] and OS [HR, 1.98 (95% CI 1.20-3.27; p = 0.008)] than those with lower CCI. CONCLUSIONS: High CCI was associated with a higher risk of disease progression as well as overall mortality in mUC patients treated with second-line pembrolizumab.

Iliac vein variation in the sacral promontory on three-dimensional computed tomography angiography: a prospective observational study before laparoscopic sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: Venous injury may occur during exposure of the anterior longitudinal ligament at the anterior sacral promontory (SP). We aimed to quantitatively measure the extent of the vascular window (VW) in front of the SP in patients with internal iliac vein (IIV) variations using preoperative three-dimensional computed tomography angiography (3DCTA). We hypothesized that patients with IIV variations would have a narrow VW. METHODS: This prospective observational study included patients scheduled for laparoscopic sacrocolpopexy (LSC) between July 2022 and April 2023 who underwent preoperative 3DCTA. The primary endpoint was the VW measurement in the standard and variant IIV groups using 3DCTA before LSC. The secondary endpoint was the difference between the two IIV groups adjusted for age, body mass index, hypertension, and diabetes using an analysis of covariance (ANCOVA) model. Multiple regression analysis was performed to analyze the effect of factors on the distance from the SP to great vascular bifurcations. RESULTS: There were 20 cases of IIV variation (20.2%). VW was 28.8 ± 12.4 mm in the variant group and 39.6 ± 12.6 mm in the standard group (p = 0.001). In the ANCOVA model, IIV variations affected VW (coefficient, -11.8; 95% confidence interval [CI], -18.4 to -5.08, p < 0.001). Multivariate analysis revealed that the aorta-SP distance decreased with age (coefficient, -0.44; 95% CI, -0.77 to -0.11, p = 0.009). CONCLUSIONS: One in five women has a vascular variant at the SP that restricts the "safe" zone of fixation to < 3 cm.

Predictive factors for disease progression after salvage radiation therapy in biochemical recurrent patients treated by radical prostatectomy.

Objective: Salvage radiation therapy (SRT) is standard treatment for patients after radical prostatectomy (RP). However, the optimal timing of SRT remains to be elucidated. Material and methods: We retrospectively reviewed 133 prostate cancer (PCa) patients who underwent SRT for biochemical recurrence after RP. Disease progression was defined as repeated prostate-specific antigen (PSA) level more than 0.2 ng/mL, greater than the post-SRT nadir or radiographic progression. A receiver operating characteristic curve analysis was used to identify the optimal pre-SRT PSA level for predicting progression after SRT. Cox regression analyses were performed to elucidate the association between clinicopathologic characteristics and disease progression. Results: Fifty-one PCa patients (38.4%) experienced disease progression after SRT. The optimal cutoff value of the pre-SRT PSA for predicting disease progression was 0.44 ng/mL. In multivariable analysis, pre-SRT PSA >0.44 ng/mL was a significant independent predictor of post-SRT disease progression [hazard ratio (HR): 2.02, P = 0.02]. Although the pre-SRT PSA >0.44 ng/mL did not maintain its independent association with disease progression in the multivariable analysis of patients with adverse pathology (HR: 1.63, P = 0.22), PSA within 4 weeks after RP as a continuous variable was significantly associated with disease progression (HR: 1.19, P = 0.04). Conclusions: Our results highlight that in PCa patients who undergo RP, SRT should be performed before their PSA reaches 0.44 ng/mL. In patients with adverse pathology disease, a high PSA level within the 4 weeks after RP might identify those who are likely to have disease progression, and these patients might require systemic therapy.

Comparison of outcomes of laparoscopic sacrocolpopexy with concomitant supracervical hysterectomy or uterine preservation.

INTRODUCTION AND HYPOTHESIS: Sacrocolpopexy was traditionally performed for post-hysterectomy prolapse or during concurrent hysterectomy. Sacrocolpopexy outcome with uterine preservation is poorly investigated. This study compared outcomes of laparoscopic sacrocolpopexy with concurrent supracervical hysterectomy or uterine preservation. METHODS: This retrospective study compared data of patients with pelvic organ prolapse who underwent laparoscopic sacrocolpopexy with uterine preservation with the data of controls who underwent laparoscopic sacrocolpopexy with supracervical hysterectomy. We analyzed composite failure in uterine preservation versus concurrent supracervical hysterectomy (primary objective) and evaluated factors associated with the primary outcome of composite failure after laparoscopic sacrocolpopexy with preservation or supracervical hysterectomy (secondary objective). Composite failure was defined as subjective bulge symptoms, reoperation, or anatomical prolapse. Cox models indicated time to composite failure as an endpoint. RESULTS: Of 274 patients, 232 underwent laparoscopic sacrocolpopexy with supracervical hysterectomy and 42 underwent laparoscopic uterine preservation. After propensity score matching (ratio: 2, for the laparoscopic sacrocolpopexy with supracervical hysterectomy group), 56 patients (24.1%) were in the supracervical hysterectomy group and 28 (66.7%) in the uterine preservation group. All patients underwent 24 months of follow-up. The composite failure rates were 10.7% for supracervical hysterectomy and 3.6% for preservation (p=0.87). The mean estimated blood loss was 10 ml (preservation, 10.0 ml [5.0-10.0] versus supracervical hysterectomy, 10.0 ml [10.0-15.0]; p=0.007). In the Cox proportional hazards model, higher preoperative body mass index and the point Ba increased composite failure risk. CONCLUSIONS: Although not statistically significant, composite failure in the two techniques is likely clinically meaningful.

Medium-Term Risk of Recurrent Pelvic Organ Prolapse within 2-Year Follow-Up after Laparoscopic Sacrocolpopexy.

Objective: The present study was performed to determine the risk of recurrent pelvic organ prolapse (POP) within 2 years after laparoscopic sacrocolpopexy (LSC) in patients with uterovaginal prolapse. Materials and Methods: A retrospective comparative study was performed in a population of 204 patients over a 2-year follow-up period following LSC with concomitant supracervical hysterectomy or uterine preservation at a single urological clinic between 2015 and 2019. The primary outcome was surgical failure following LSC in cases of POP, focusing on failures occurring before the 2ndyear of follow-up. Logistic regression analysis was used to determine the odds ratios (ORs) for surgical failure. Results: The primary outcome, surgical failure in cases of POP, occurred 2 years after the initial surgery in 19 of the 204 patients (9.3%) (95% confidence interval [CI], 5.7% - 14.2%). Surgical failure was most common in the anterior compartment (n = 10, 4.9%), and further surgery was performed in seven of the patients with surgical failure (3.4%). The poor primary outcome was predicted by lysis of adhesions (OR, 7.5, 95% CI, 1.6-33.8, P = 0.008) and preoperative POP stage IV (OR, 3.5; 95% CI, 1.1-10.8, P = 0.03) on multivariable logistic regression analysis. Conclusion: The overall rate of surgical failure following LSC in our cohort was 9.3% over the 2-year follow-up period after surgery, and preoperative prolapse stage IV was associated with a higher risk of recurrence.

Upfront Androgen Receptor-Axis-Targeted Therapies in Men with De Novo High-Volume Metastatic Hormone-Sensitive Prostate Cancer.

PURPOSE: The extent of effectiveness of upfront androgen receptor-axis-targeted therapies (ARAT) versus total androgen blockade (TAB) in improving prostate cancer-specific survival (CSS) and progression-free survival (PFS) in a real-world sample of Japanese patients with high-volume mHSPC remains unclear. We, therefore, investigated the efficacy and safety of upfront ARAT versus bicalutamide for de novo high-volume mHSPC in Japanese patients. MATERIAL AND METHODS: This was a multicenter retrospective study that analyzed CSS, clinical PFS, and adverse events (AEs) in 170 patients with newly diagnosed high-volume mHSPC. Fifty-six patients were treated with upfront ARAT, and 114 of them were prescribed bicalutamide in addition to ADT between January 2018 and March 2021. The primary and secondary endpoints were CSS and PFS, respectively. A 1:1 nearest neighbor propensity score matching (PSM) with a caliper of 0.2 was performed to match the ARAT group to TAB patients. RESULTS: During the follow-up for a median of 21.5 months, the median CSS was not reached and 37 months in the upfront ARAT and total androgen blockade (TAB) groups, respectively (log-rank test: P = 0.006) by propensity score matching (PSM). Moreover, while the PFS of ARAT was unreached, the median PFS of TAB was 9 months (log-rank test: P < 0.001). Nine patients discontinued ARAT owing to grade ≥ 3 AEs; one patient who was treated with TAB had a grade 3 AE. CONCLUSION: Upfront ARAT significantly prolonged the CSS and PFS of patients with high-volume mHSPC better than TAB, although ARAT was associated with a higher rate of grade ≥ 3 AEs. Upfront ARAT can be more beneficial for patients with de novo high-volume mHSPC than TAB.

Percutaneous cryoablation versus partial nephrectomy for cT1b renal tumors: An inverse probability weight analysis.

PURPOSE: To investigate differential clinical outcomes in patients treated with partial nephrectomy (PN) vs. percutaneous cryoablation (PCA) for cT1b renal tumors. MATERIALS AND METHODS: We retrospectively analyzed the records of 119 patients who had undergone PN (n = 90) or PCA (n = 29) for cT1b renal tumors. Inverse probability weighting (IPW) was used for balancing patient demographics, including renal function and tumor complexity. Perioperative complications, renal function preservation rates, and oncological outcomes such as local recurrence-free, metastasis-free, cancer-specific, and overall survival were compared using IPW-adjusted restricted mean survival times (RMSTs). RESULTS: PCA was more likely to be selected for octogenarians (odds ratio: 11.4, 95% confidence interval [CI]: 3.33-45.1). During the median follow-up of 43 months in the PCA group and 36.5 months in the PN group, unablated local residue or local recurrence was noted in 6 patients in the PCA group and local recurrence was noted in 4 patients in the PN groups. Of the 6 patients in the PCA group, 4 underwent salvage PCA, and local control had been achieved at the last visit. In the IPW-adjusted population, PCA had significantly worse local recurrence-free survival compared with PN (IPW-adjusted RMST difference: -22.7 months, 95% CI: -45.3 to -0.4, P = 0.046). IPW-adjusted RMST for metastasis-free survival (P = 0.23), cancer-specific survival (P = 0.77), and overall survival (P = 0.11) did not differ between PCA and PN. In addition, PN was not a predictor for local control failure at the last visit (odds ratio: 0.30, 95%CI: 0.05-1.29). There were no statistically significant differences between PN and PCA in renal function preservation or overall/severe complication rates. CONCLUSIONS: In patients with cT1b renal tumor, although the local recurrence rate is higher for PCA than for PN, PCA provides comparable distant oncologic outcomes. PCA can be an alternative treatment option for elderly, comorbid patients, even those with cT1b renal tumors.

Effectiveness of pembrolizumab in trial-ineligible patients with metastatic urothelial carcinoma.

BACKGROUND: The KEYNOTE-045 trial showed that pembrolizumab therapy improved the survival of patients with advanced urothelial carcinoma (UC). However, its effectiveness in trial-ineligible patients remains unclear. MATERIALS AND METHODS: We conducted a multicenter retrospective study to evaluate the effectiveness of pembrolizumab in patients with metastatic UC who were trial-ineligible. The data of 164 consecutive patients with platinum-treated metastatic UC who received pembrolizumab as second-line therapy were analyzed. Trial eligibility was assessed using the KEYNOTE-045 criteria. Inverse probability of treatment weighting (IPTW) was used to balance patient characteristics. Overall survival (OS) and progression-free survival (PFS) were examined using the IPTW-adjusted Kaplan-Meier method. IPTW-adjusted restricted mean survival times (RMSTs) were compared between ineligible and eligible patients. RESULTS: Seventy-five patients (45.7%) were classified as ineligible based on the KEYNOTE-045 criteria. Baseline hemoglobin concentration of less than 9.0 g/dL was the most common reason for trial protocol violation (N = 23 [14.0%]). An IPTW-adjusted logistic regression model showed that the trial-eligibility was not significantly associated with objective response (OR: 0.65, 95% CI: 0.32 to 1.29, P = 0.22). Ineligible patients had similar RMST for PFS (difference: 3.8 months, 95% CI: -1.6 to 9.3, P = 0.17) and RMST for OS (difference: 1.4 months, 95% CI: -5.4 to 8.2, P = 0.93) compared with eligible patients. CONCLUSIONS: This study suggests that the effectiveness of pembrolizumab may be retained in ineligible patients with platinum-treated metastatic UC. Expanding trial eligibility criteria for these patients may be beneficial.

Medium-term outcomes 2 years after laparoscopic sacrocolpopexy: a retrospective cohort study in Japan.

This study was performed to investigate medium-term outcomes and reoperation rates after laparoscopic sacrocolpopexy (LSC). We examined 119 patients undergoing LSC for symptomatic pelvic organ prolapse (POP). The primary outcomes were subjective failure and anatomical failure at 2 years; a score ≥ 2 on question 3 of the PFDI-20 was considered to indicate subjective failure. POP-Q stage 2 or higher in any compartment was considered to indicate anatomical failure. Secondary outcomes were reoperations for POP recurrence, mesh-related complications, and stress urinary incontinence (SUI). The rates of subjective failure and anatomical failure were 4.2% (n = 5) and 9.2% (n = 11), respectively. Reoperations were needed in 13.4% (n = 16) of patients, including SUI with tape procedure in 7.5% (n = 9), POP recurrence in 4.2% (n = 5), and mesh-related complications in 1.6% (n = 2). The subjective failure rate at 2 years after LSC was acceptably low.Impact StatementWhat is already known on this subject? Laparoscopic sacrocolpopexy (LSC) has clinical efficacy equivalent to open sacrocolpopexy, and there is evidence that LSC involves less blood loss and shorter length of hospital stay. However, there is still insufficient evidence to assess medium-term outcomes after LSC in Japan.What the results of this study revealed? The findings of this study showed excellent medium-term rates of subjective failure (4.2%) and anatomical failure (8.4%) after LSC. We demonstrated that patients with persistent postoperative vaginal bulge (subjective failure) also had no improvement in postoperative urinary and colorectal symptoms. Our cohort had low rates of reoperation (13.4%) after LSC. The most common reoperations were for stress urinary incontinence (SUI) (7.5%), followed by pelvic organ prolapse (POP) recurrence (4.2%) and mesh-related complications (1.6%).What are the implications of these findings in clinical practice and/or further research? This study showed that LSC is a safe and effective treatment for POP. Comparative evaluation of anatomical outcomes and the patient's condition is required to understand the extent to which LSC positively impacts a woman's pelvic floor-related quality of life.

Novel insight into the correlation between hernia orifice of cystocele and lower urinary tract function: a pilot study.

BACKGROUND: It has been hypothesized that women with significant pelvic organ prolapse (POP), particularly of the anterior vaginal wall, may have voiding dysfunction (VD). Although the VD mechanism due to cystocele is not fully understood, different vaginal compartments have rarely been closely examined. This study attempted to further elucidate the correlation between POP and VD through a new subgroup classification using cystoscopy. METHODS: This study reviewed clinical records of 49 women who underwent cystocele repair. All patients were scheduled for laparoscopic sacrocolpopexy, preoperatively underwent uroflowmetry and postvoid residual urine volume (PVR) measurement, and completed pelvic floor function questionnaires. Bladder examination by cystoscopy was additionally performed using the lithotomy position with the Valsalva maneuver. RESULTS: Subjects were divided into four groups according to hernia orifice presence determined by cystoscopy, which included the trigone type, posterior wall type, trigone and urethra type, and trigone and posterior wall type. The posterior wall type had statistically higher PVR values versus the trigone and posterior wall type (P = 0.013). The posterior wall type had statistically lower values for average urine flow rate versus the urethra and trigone type (P = 0.020). There were no significant differences noted in the pelvic floor function questionnaires among the four groups. CONCLUSIONS: A new bladder defect classification based upon hernia orifice location was associated with lower urinary tract function. Posterior wall hernia presence caused significant voiding function deterioration. This new subgroup classification, which can more clearly identify and indicate bladder function, is also comparable among patients.

Severity of Cystocele and Risk Factors of Postoperative Stress Urinary Incontinence after Laparoscopic Sacrocolpopexy for Pelvic Organ Prolapse.

Objectives: Knowledge on the severity of cystocele and incidence of postoperative stress urinary incontinence (SUI) after prolapse repair is lacking. This study investigated the incidence and risk factors of postoperative SUI following laparoscopic sacrocolpopexy (LSC). Materials and Methods: We retrospectively reviewed the charts of 83 women without occult SUI who underwent LSC for pelvic organ prolapse and developed SUI over 3 months postoperatively. We used Fisher's exact test, the Mann-Whitney U-test, and logistic regression for statistical data analyses. Results: After 3 months, the incidences of postoperative SUI were 50% and 24% in those who did and did not report preoperative SUI, respectively. Eventually, postoperative SUI was reported by 39% and 9% of the women with and without preoperative SUI, respectively. Increased Ba (point of maximal anterior vaginal wall prolapse) measurement (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.0-2.06; P = 0.04) and preoperative SUI (OR, 3.95; 95% CI, 1.14-13.7; P = 0.03) were the risk factors for postoperative SUI. Conclusion: Our findings suggest that counseling regarding the risk of postoperative SUI should be conducted for women with preoperative advanced cystocele or bothersome SUI.

Effectiveness of pembrolizumab in patients with urothelial carcinoma receiving proton pump inhibitors.

BACKGROUND: The association of concurrent proton pump inhibitor (PPI) use with treatment outcome of metastatic urothelial carcinoma (UC) remains controversial. MATERIALS AND METHODS: We retrospectively analyzed the records of 227 patients with platinum-treated metastatic UC treated with pembrolizumab. The primary outcome was overall survival (OS). Immune progression-free survival (iPFS) and objective response per immune response evaluation criteria in solid tumors were also compared. Inverse probability of treatment weighting (IPTW)-adjusted multivariable Cox regression models and an IPTW-adjusted multivariable logistic regression model were used to evaluate the oncological outcomes. Furthermore, the heterogeneity of the treatment effect on OS was examined using interaction terms within the IPTW-adjusted univariate Cox regression models. RESULTS: Overall, 86 patients (37.9%) used PPIs. After weighting, no significant differences in patient characteristics were observed between PPI users and non-users. PPI use was significantly associated with a shorter OS (hazard ratio [HR]: 2.02, 95% confidence interval [CI]: 1.28-3.18, P = 0.003) and iPFS (HR: 1.70, 95% CI: 1.23-2.35, P = 0.001). Although not statistically significant, PPI use was associated with objective response as well (OR: 0.61, 95% CI: 0.36-1.02, P = 0.06). The interaction analyses showed that the effect of PPI significantly decreased with age (HR: 0.97, 95% CI: 0.93-1.00, P[interaction] = 0.048) and was increased in males (HR: 2.97, 95% CI: 1.10-8.05, P[interaction] = 0.032). CONCLUSIONS: PPI use was significantly associated with worse survival of patients with metastatic UC treated with pembrolizumab. Furthermore, the results suggested that its effects decreased with age and was increased in males.

Clinical benefit of continuing pembrolizumab treatment beyond progression in patients with metastatic urothelial carcinoma.

BACKGROUND: There has been no clinical evidence to justify continued pembrolizumab therapy beyond progression in patients with metastatic urothelial carcinoma (UC). MATERIALS AND METHODS: We conducted a multicenter retrospective study evaluating the clinical efficacy of continued use of pembrolizumab beyond progression in patients with metastatic UC. Data from 51 patients with metastatic UC, who developed progression during second-line pembrolizumab therapy, were analyzed. Progression was defined based on the Immunotherapy Response Evaluation Criteria in Solid Tumors. The outcome was overall survival (OS). The association between continued treatment, OS, and the risk of all-cause mortality was tested using log-rank test, conventional and time-dependent Cox regression models. RESULTS: No significant difference in patient characteristics was noted between patients continuing pembrolizumab beyond progression (N = 21) and those discontinuing pembrolizumab (N = 30). Median OS was significantly longer in the continuation group (17.8 vs. 8.8 months; P = 0.038). A multivariable conventional Cox regression model identified continued pembrolizumab administration as a significant independent prognostic factor of all-cause mortality (hazard ratio [HR]: 0.21, 95% confidence interval [CI]: 0.05-0.90, P = 0.036), irrespective of the time from treatment initiation to progression and concurrent clinical progression. Further, longer duration of pembrolizumab treatment beyond progression was independently associated with a reduced risk of all-cause mortality in a multivariable time-dependent Cox regression model, when used as a time-dependent variable (HR: 0.07, 95% CI: 0.01-0.45, P = 0.006). CONCLUSIONS: Continued pembrolizumab administration beyond progression might be beneficial in patients with metastatic UC who were clinically stable.

Laparoscopic sacrocolpopexy for pelvic organ prolapse in the elderly: safety and outcomes.

Due to its low postoperative complication rate, vaginal surgery is the preferred intervention for pelvic organ prolapse (POP) in elderly patients. We aimed to assess outcomes and perioperative complication rates associated with laparoscopic sacrocolpopexy (LSC) in elderly women. We retrospectively reviewed the medical records of 74 consecutive patients [52 (70.3%) aged <75 years; 22 (29.7%) aged ≥75 years] with POP who underwent LSC between August 2015 and December 2017. We evaluated preoperative risks using the Charlson Comorbidity Index (CCI) and complications, using the Clavien-Dindo grading (CDG). No between-group differences were observed in CCI. CDG indicated fewer perioperative complications in patients aged >75 years. Anatomical success rates at 15 months were 95.5% and 90.4% in patients aged ≥75 and <75 years, respectively. LSC has a high anatomical correction rate and few perioperative complications regardless of age. Thus, the appropriate surgical intervention method would depend on the patient's health and comorbidities.IMPACT STATEMENTWhat is already known on this subject? Laparoscopic sacrocolpopexy (LSC) is a superior method to vaginal surgery because of its anatomical and functional outcomes, particularly regarding sexual activity.What do the results of this study add? In this single-center study with a 15-month follow-up, we demonstrated that LSC has a high anatomical correction rate and few perioperative complications regardless of age at the time of surgery. Furthermore, there was no significant difference in the rate of complications between the ≥75 and <75 years groups. Thus, LSC may be considered for women aged >75 years. However, in these elderly patients, the surgical method should be determined according to their health status and medical comorbidities.What the implications are of these findings for clinical practice and/or further research? Age should not be the basis for exclusion from laparoscopic procedures. Moreover, LSC is a suitable and valid option for elderly women with POP. As the study population consisted of a homogenous group of Japanese women, it lacks generalisability. Studies evaluating these outcomes are required in other populations.

Prognostic model with alkaline phosphatase, lactate dehydrogenase and presence of Gleason pattern 5 for worse overall survival in low-risk metastatic hormone-sensitive prostate cancer.

BACKGROUND: Randomized trials showed the survival benefits of the combined use of androgen receptor axis-targeted agents with androgen deprivation therapy in metastatic hormone-sensitive prostate cancer (mHSPC), regardless of the risk. However, treating patients with low-risk mHSPC with such intensive treatment is still debatable. METHODS: This retrospective study included 155 low-risk patients among 467 mHSPC patients treated in our affiliated institutions. The association between predictive factors and treatment outcomes was estimated using the Kaplan-Meier method and log-rank test. Predictive factors for castration resistant prostate cancer (CRPC)-free survival were investigated using Cox regression analyses. RESULTS: During the median follow-up of 39 months, 38.7% of patients developed CRPC and 14.2% died. In the multivariate analyses, a presence of Gleason pattern 5 (hazard ratio [HR] 2.04), high alkaline phosphatase (HR 1.007) and high lactate dehydrogenase (HR 1.009) were significant predictive factors for shorter CRPC-free survival. Finally, 155 patients were stratified into favorable- and unfavorable-risk groups based on the numbers of the predictive factors. The overall survival (OS) in the unfavorable-risk group (total scores: 2-3) was significantly worse than that of the favorable-risk group (total score: 0-1) (P = 0.02). This prognostic model was assessed with 50 low-risk mHSPC patients from the external validation dataset and found both the time to CRPC, and the OS in the unfavorable-risk group was significantly worse than that of the favorable-risk group (P < 0.01). CONCLUSIONS: The combination of Gleason pattern 5, high alkaline phosphatase and lactate dehydrogenase can predict those with worse OS in low-risk mHSPC patients.

Bladder cancer invasion along a tension-free vaginal mesh.

INTRODUCTION: The effect of synthetic mesh after pelvic organ prolapse surgery on the progression of bladder cancer remains unclear. CASE PRESENTATION: A 79-year-old woman who underwent a tension-free vaginal mesh procedure 8 years prior was diagnosed with carcinoma in situ of the bladder. Although intravesical Bacillus Calmette-Guérin therapy was started, the tumor rapidly became muscle invasive. Laparoscopic radical cystectomy was performed following radiochemotherapy; however, the tumor extended to the left internal obturator muscle along the mesh arm. Pathological findings showed desmoplastic high-grade urothelial carcinoma infiltrating around the mesh. Finally, cancer recurred rapidly in the left internal obturator muscle. CONCLUSION: Synthetic mesh can become an abnormal anatomical pathway for tumor infiltration. Therefore, in high-risk bladder cancer patients who underwent a tension-free vaginal mesh procedure, radical cystectomy should be performed without delay before the tumor invades the perivesical tissue.

Impact of Dose-Effect in Smoking on the Effectiveness of Pembrolizumab in Patients with Metastatic Urothelial Carcinoma.

BACKGROUND: Subgroup analysis of KEYNOTE-045 suggested that cigarette smoking had a positive impact on the effectiveness of pembrolizumab in patients with advanced urothelial carcinoma (UC), whereas studies on other cancers treated with immune checkpoint inhibitors reported inconsistent results. OBJECTIVES: This study aimed to examine the association between smoking-related factors and the effectiveness of pembrolizumab in patients with metastatic UC. PATIENTS AND METHODS: This multicenter retrospective study was conducted using data from 95 patients with metastatic UC treated with pembrolizumab. The primary outcomes were progression and all-cause mortality. Time-to-event outcomes were compared with smoking history and lifetime smoking exposure at treatment initiation. Survival curves were compared using the log-rank test, with hazard ratios (HRs) estimated from Cox regression models. Cubic spline regression analysis was used to depict event hazards. RESULTS: We identified 32 (34.7%) patients with heavy smoking exposure (≥ 25 pack-years). Moreover, 19 (20.0%), 36 (37.9%), and 40 (42.1%) patients were current, former, and never smokers, respectively. Multivariable models showed that heavy smoking exposure was significantly associated with lower risk of progression (HR 0.58; 95% confidence interval (CI) 0.35-0.97; P = 0.047) and all-cause mortality (HR 0.30; 95% CI 0.11-0.82; P = 0.019). Cubic spline regression analyses revealed a dose-effect relationship. No significant association was observed between smoking history alone and effectiveness of pembrolizumab. CONCLUSIONS: Lifetime smoking exposure plays a significant role in the effectiveness of pembrolizumab in patients with metastatic UC.

Comparison of the Immunotherapy Response Evaluation Criteria in Solid Tumours (iRECIST) with RECIST for capturing treatment response of patients with metastatic urothelial carcinoma treated with pembrolizumab.

OBJECTIVE: To evaluate the clinical usefulness of Immunotherapy Response Evaluation Criteria in Solid Tumours (iRECIST) in patients with metastatic urothelial carcinoma (UC) treated with pembrolizumab. The iRECIST is designed to accurately capture the tumour response treated with immunotherapy. PATIENTS AND METHODS: We conducted a multicentre retrospective study evaluating the clinical utility of iRECIST in 91 patients with metastatic UC treated with second-line pembrolizumab. The objective response (OR) and time to progression (TTP) in accordance with both iRECIST and RECIST version 1.1 were compared with overall survival (OS) and risk of all-cause mortality, and analysed using log-rank and multivariable Cox regression models, respectively. Predictive performance of the criteria was studied using Harrell's concordance index (c-index). The clinical usefulness of each criterion was compared using decision curve analysis. RESULTS: Of 57 patients with progressive disease per RECIST, a considerable number of patients were reclassified to immune stable disease (six, 10.5%), immune partial response (two, 3.5%), and immune complete response (two, 3.5%) per iRECIST. Multivariable Cox regression models showed that both OR (hazard ratio [HR] 0.10, 95% confidence interval [CI] 0.03-0.35; P = 0.001) and TTP (HR 0.59, 95% CI 0.46-0.77; P < 0.001) per iRECIST were significantly associated with all-cause mortality. Furthermore, iRECIST had a significant, increased predictability of OS compared with RECIST (OR, c-index: 0.70, increase: 0.04, P = 0.046; TTP, c-index: 0.88, increase: 0.07, P = 0.039). On decision curve analysis, iRECIST presented better net benefit gains than did RECIST. CONCLUSIONS: Compared with RECIST, iRECIST could more accurately predict OS of patients with metastatic UC treated with pembrolizumab. The iRECIST has the potential to be a new standard for tumour response evaluation of these patients.

Modified Glasgow prognostic score is a pre-surgical prognostic marker of disease mortality in upper urinary tract urothelial carcinoma.

BACKGROUND: To investigate the prognostic value of pre-surgical modified Glasgow prognostic score in upper urinary tract urothelial carcinoma patients treated with radical nephroureterectomy. METHODS: We retrospectively reviewed the clinical records of 273 urinary tract urothelial carcinoma patients treated with radical nephroureterectomy. The modified Glasgow prognostic score was evaluated based on pre-surgical serum C-reactive protein and albumin. Association of modified Glasgow prognostic score with recurrence-free survival, cancer-specific survival and overall survival rates was estimated using Kaplan-Meier method and log-rank test was used to compare survival outcome. Cox regression analyses were performed for the assessment of the modified Glasgow prognostic score with recurrence-free survival, cancer-specific survival and overall survival. RESULTS: Of total 273 patients, the modified Glasgow prognostic score 0, 1 and 2 were assigned in 216 (79%), 45 (17%) and 12 (4%), respectively. The recurrence-free survival, cancer-specific survival and overall survival of urinary tract urothelial carcinoma patients with modified Glasgow prognostic score 2 were significantly worse than those with modified Glasgow prognostic score 0. On univariate analysis, modified Glasgow prognostic score 2 was associated with worse recurrence-free survival, cancer-specific survival and overall survival (all P value <0.01). On multivariate analyses, modified Glasgow prognostic score 2 was independently associated with worse cancer-specific survival and overall survival (hazard ratio: 4.73, 95% confidence interval: 1.31-17.2 and hazard ratio: 3.66, 95% confidence interval: 1.08-12.4, respectively). In the subgroup analyses of advanced urinary tract urothelial carcinoma patients, modified Glasgow prognostic score 2 was independently associated with worse recurrence-free survival (hazard ratio 4.31, 95% confidence interval: 1.69-11.1). CONCLUSIONS: Pre-surgical modified Glasgow prognostic score independently predicts cancer-specific survival and overall survival of urinary tract urothelial carcinoma patients. Assessment of pre-surgical modified Glasgow prognostic score status could help identifying the worse survivor of urinary tract urothelial carcinoma patients.