Cost-effectiveness of nivolumab plus gemcitabine-cisplatin as first-line treatment for advanced urothelial carcinoma in China and the United States.

Objective: Nivolumab, recently proven in a phase 3 clinical trial (CheckMate 901) to enhance survival when combined with gemcitabine-cisplatin for advanced urothelial carcinoma. This study aimed to assess its cost-effectiveness against gemcitabine-cisplatin alone, from US and Chinese payers' perspectives. Methods: A partitioned survival model was established to assess the life-years, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs) of nivolumab plus gemcitabine-cisplatin versus gemcitabine-cisplatin alone as first-line treatment for advanced urothelial carcinoma. Univariate, two-way, and probabilistic sensitivity analyses were conducted to assess the model's robustness. Additionally, subgroup analyses were performed. Results: Nivolumab plus gemcitabine-cisplatin and gemcitabine-cisplatin achieved survival benefits of 4.238 life-years and 2.979 life-years for patients with advanced urothelial carcinoma, respectively. Compared with gemcitabine-cisplatin, nivolumab plus gemcitabine-cisplatin resulted in ICERs of $116,856/QALY in the US and $51,997/QALY in China. The probabilities of achieving cost-effectiveness at the current willingness-to-pay thresholds were 77.5% in the US and 16.5% in China. Cost-effectiveness could be reached if the price of nivolumab were reduced to $920.87/100mg in China. Subgroup analyses indicated that the combination had the highest probability of cost-effectiveness in patients under 65 or with an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 in the US and China. Conclusion: Nivolumab plus gemcitabine-cisplatin first-line treatment for advanced urothelial carcinoma results in longer life expectancy than gemcitabine-cisplatin, but is not cost-effective in China at current price. However, cost-effectiveness is likely to be achieved in most patient subgroups in the US.

The prognostic value of preoperative plasma fibrinogen in Asian patients with urothelial cancer: a systematic review and meta-analysis.

Objective: We conducted this meta-analysis to comprehensively explore the prognostic value of the preoperative plasma fibrinogen in Asian patients diagnosed with urothelial cancer (UC). Methods: After a systematic search of Web of Science, PubMed, and Embase before May 2024, we included 10 studies in our meta-analysis. The hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression free survival (PFS) were estimated using fixed effect model. Results: This meta-analysis included a total of 2875 patients. UC patients with an elevated preoperative plasma fibrinogen had worse OS (pooled HR: 2.13, 95% CI: 1.81-2.51; P<0.001), CSS (pooled HR: 2.22, 95% CI: 1.83-2.70; P<0.001), RFS (pooled HR: 1.90, 95% CI: 1.59-2.27; P<0.001), and PFS (pooled HR: 2.12, 95% CI: 1.36-3.29, P=0.001). No significant heterogeneity or publication bias was found. Additionally, statistically significant pooled HRs were also calculated in subgroup analysis when stratified by cancer type, country, and cut-off value. Conclusions: The presence of elevated preoperative plasma fibrinogen levels is significantly correlated with unfavorable tumor outcomes in UCs.

Cost-effectiveness of first-line enfortumab vedotin in addition to pembrolizumab for metastatic urothelial carcinoma in the United States.

Background and objective: The EV-302 trial found that the combination of enfortumab vedotin (EV) with pembrolizumab significantly improved survival for patients with metastatic urothelial carcinoma (mUC). However, given the high cost of the drugs, there is a need to assess its value by considering both efficacy and cost. This study assessed the cost-effectiveness of EV plus pembrolizumab as a first-line treatment for patients with mUC from the perspective of U.S. payers. Methods: A Markov model was developed to compare the lifetime costs and effectiveness of EV in combination with pembrolizumab with chemotherapy in the treatment of mUC patients from U.S. payer perspective. Life-years (LYs), quality-adjusted LYs (QALYs), and lifetime costs were estimated. One-way, two-way and probabilistic sensitivity analyses were conducted to evaluate model uncertainty. Additionally, subgroup analyses were performed. Results: Compared to chemotherapy, the combination of EV and pembrolizumab provided an additional 2.10 LYs and 1.72 QALYs, at an incremental cost of $962,240.8 per patient. The incremental cost-effectiveness ratio (ICER) is $558,973 per QALY. Subgroup analysis indicated that patients ineligible for cisplatin treatment had a lower ICER compared to those who were eligible for cisplatin. Conclusions: From the perspective of US payers, at a willingness-to-pay threshold of $150,000 per QALY, the combination of EV and pembrolizumab is estimated to not be cost-effective compared to traditional chemotherapy in the first-line treatment of mUC patients.

Immunotherapy Plus Chemotherapy Versus Chemotherapy Alone as First-Line Treatment for Advanced Urothelial Cancer: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Platinum-based chemotherapy (CTX) has historically been the primary treatment for advanced urothelial cancer (aUC), with limited alternative options. The therapeutic landscape experienced a paradigm shift following the results of the EV-302 and Checkmate-901 trials, which led to the approval of Enfortumab vedotin plus pembrolizumab (EV-P) as the preferred first-line treatment, and nivolumab plus CTX for those unable to receive the preferred regimen. Currently, further investigations are underway to explore PD-1 and PD-L1 inhibitors in the initial treatment of aUC. PATIENTS AND METHODS: We conducted a systematic search across PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) comparing immune checkpoint inhibitors (ICI)-CTX combinations versus CTX alone as first-line treatment for advanced UC. Employing a random-effects model, we pooled hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Our analysis encompassed 3 RCTs, involving 2162 participants, with 51.16% randomized to combination therapy with platinum-based CTX. Compared to CTX alone, immune-chemotherapy significantly improved overall survival (HR 0.84; 95% CI 0.75-0.93; P < .01), progression-free survival (HR 0.78; 95% CI 0.70-0.86; P < .01), and objective response rate (RR 1.20; 95% CI 1.06-1.36; P < .01), while elevating the risk of immune-related adverse events (P-value = .02). CONCLUSION: In this meta-analysis of RCTs, ICI plus CTX demonstrated a significant association with improved survival at the expense of an increased risk of immune-related adverse events. Therefore, our findings suggest that this combination should be considered as an initial treatment for aUC in platinum-eligible patients who cannot receive EV-P.

Central pathology review and its prognostic value in upper tract urothelial carcinoma patients: a nationwide multi-institutional study.

The prognostic value of central pathology review in upper urinary tract cancer (UTUC) remains inadequately addressed in existing literature. In this study, we conducted an extensive central pathology review and presented its influence on multi-center UTUC studies. We conducted a retrospective review of patients who underwent radical nephroureterectomy or segmental resection for UTUC to determine eligibility for central pathology review. In the Taiwan UTUC Collaboration cohort, 377 cases met the criteria for pathology review. We assessed agreement between pathologists using both the total percentage of agreement and simple kappa statistics. The prognostic implications of original and review pathology for various parameters were examined using the Cox regression model. This study included 209 female and 168 male participants. Pathology review revealed substantial interobserver variability in pT staging, with a particularly high rate of pT2 cases being upgraded to pT3 upon central review (17/70 pT2 stage made by local pathologists were finally confirmed as pT3 disease by the review pathologist). The local pathologist cohort identified fewer significant histological predictors in survival models compared to the review pathology cohort. Advanced pT stage, perineural invasion (PNI), and positive surgical margin were independent predictors of poorer overall survival and cancer-specific survival. PNI, lymphatic vascular invasion, and positive surgical margin were independent predictors of disease recurrence. Substantial interobserver variability in histological assessment underscores the importance of centralized pathology review for both multi-center studies and accurate post-operative management of UTUC patients. Advanced stage, perineural invasion, and margin status were significant histological predictors of oncological outcomes.

Immunotherapy-Based Combinations in First-Line Urothelial Cancer: A Systematic Review and Individual Patient Data (IPD) Meta-Analysis.

INTRODUCTION: Platinum-based chemotherapy represents the standard of care (SoC) for the first-line treatment of advanced urothelial carcinoma (mUC). The benefit of adding immune checkpoint inhibitors (ICIs) to platinum-based chemotherapy was recently investigated. We performed an individual patient data (IPD) meta-analysis of phase 3 clinical trials comparing ICI-based treatments. METHODS: A systematic literature search was conducted on the MEDLINE and CENTRAL databases. The results were filtered by including only reports on clinical trials or randomized clinical trials from 2018 to 2023, including 3047 patients from four clinical trials (EV302, CHECKMATE-901, IMVIGOR130, KEYNOTE-361). An IPD meta-analysis was performed by reconstructing IPD from Kaplan-Meier curves. The primary endpoints were overall survival (OS) and progression-free survival (PFS) of Pembrolizumab + EV compared to experimental arms of the other trials of immunotherapy + chemotherapy. RESULTS: The OS analysis showed an advantage of IPD from EV302 vs. all the other trials. For EV302 vs. KEYNOTE-361, the HR was 0.51; for EV302 vs. IMVIGOR130, the HR was 0.47; and for EV302 vs. CHECKMATE-901, the HR was 0.66 (CI 95% 0.51-0.85). In the PFS analysis, the EV302 arm showed a statistically significant advantage compared to CHECKMATE-901 (HR 0.66) and versus IMVIGOR130 (HR 0.51). LIMITATIONS: By using reconstructed IPD curves, it was not possible to adjust patient-level covariates, and the heterogeneity of the included population may have affected the pooled results. CONCLUSIONS: The EV302 experimental arm showed better OS and PFS when compared to the other immunochemotherapy combinations. An immunochemotherapy combination strategy at the beginning of treatment in mUC seems to be superior in terms of OS and PFS compared to platinum-based chemotherapy alone. EV-Pembrolizumab resulted to have better outcomes compared to avelumab, rather than other immunochemotherapy combinations. However, given the heterogeneity of these studies, a longer follow up and prospective trials are needed to confirm these data.

Objective Response Rate is a Surrogate Marker for Long-Term Overall Survival in Metastatic Urothelial Carcinoma Patients Treated With Immune Checkpoint Inhibitors.

BACKGROUND: This study aimed to evaluate the utility of RECIST criteria-based objective response rate (ORR) as a potential surrogate endpoint for long-term overall survival (OS) in patients with metastatic urothelial carcinoma who were treated with immune checkpoint inhibitors (ICIs). METHODS: The primary endpoint was overall ORR and OS, duration of treatment (DoR) with ICIs. ORR was analyzed using Fisher's exact test. Median follow-up and OS were estimated by using the Kaplan-Meier method. RESULTS: The median follow-up was 58 (1.15-71) months. Progression developed in 94 (47%) patients during the first 3 months of ICIs therapy. The treatment response to ICIs included complete response (CR), partial response (PR) and stable disease in 10% (n = 20), 23% (n = 46), and 20% (n = 41) of patients, respectively. The responder and nonresponder groups differed in terms of certain baseline characteristics, such as Bellmunt risk factors, and neutrophil-to-lymphocyte ratio (NLR). The 5-year OS rates for patients with CR and PR were 73% and 23%, respectively. The median DoR for CR, PR, and SD were 51.8 months (44.5-59.1), 20.7 months (16.7-24.6), and 8.8 months (5.5-12.1), respectively. Overall, 16(80%) patients with CR and 14(30%) patients with PR had an ongoing response at the time of the analysis. In the univariate analysis, NLR > 3, liver metastases, ECOG PS ≥ 1, and hemoglobin levels < 10 mg/dl, as well as the PR and CR, were all significantly associated with OS. In multivariate analysis, presence of liver metastases (HR 2.3; 95% CI, 1.3-4.2; P < .004) was found to be an independent determinant of short OS, while PR (HR 0.3; 95% CI, 0.15-0.5; P < .001) and CR (HR 0.06; 95% CI, 0.014-0.27; P < .001) were associated with improved OS. CONCLUSIONS: In conclusion, this 5-year analysis of real-world data in the setting of metastatic urothelial cancer indicated a significant correlation between ORR, especially CR, and OS in patients who received ICIs. Therefore, identifying a potential surrogate marker for survival in patients treated with ICIs would represent an important advance in the early identification of patients' response or resistance to ICIs.

Laparoscopic Versus Open Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review and Meta-Analysis of Propensity-Score Matched Studies.

BACKGROUND: The effectiveness of laparoscopic nephroureterectomy (LNU) vs open nephroureterectomy (ONU) for upper tract urothelial carcinoma (UTUC) is unclear. METHODS: We conducted a meta-analysis of studies based on propensity score-matched cohorts to compare the surgical and oncological outcomes of LNU and ONU in UTUC patients. A literature search was conducted on PubMed, Embase, and Cochrane Library until July 12, 2023. The Newcastle-Ottawa Scale was utilized to assess the quality of eligible studies. Measurements of surgical and oncological outcomes were extracted and pooled including mean difference (MD), risk ratio (RR), hazard ratios (HR), and 95% confidence intervals (CI). RESULTS: Five high-quality retrospective studies were included, totaling 6422 patients; 2080 (32.4%) underwent LNU, and 4342 (67.6%) underwent ONU. With respect to surgical outcomes, patients in the LNU group experienced less estimated blood loss and had shorter hospital stay than those in the ONU group, but there was no significant difference in complication rates and operation time. In regard to oncological outcomes, there were no significant differences between the LNU and ONU groups in 3-year overall survival (OS) and cancer-specific survival (CSS). However, 3-year intravesical recurrence free survival (IVRFS) was worse in the LNU group compared to the ONU group. CONCLUSION: LNU was associated with less estimated blood loss and shorter hospital stays than ONU, but there were no differences in OS and CSS between the surgical modalities. Nonetheless, LNU might result in poorer IVRFS than ONU.

Sacituzumab Govitecan Demonstrates Efficacy across Tumor Trop-2 Expression Levels in Patients with Advanced Urothelial Cancer.

PURPOSE: Human trophoblast cell surface antigen 2 (Trop-2) is a protein highly expressed in urothelial cancer (UC). Sacituzumab govitecan (SG) is a Trop-2-directed antibody drug conjugate with a hydrolysable linker and a potent SN-38 payload. This study explored Trop-2 expression in tumors treated with SG in cohorts 1 to 3 (C1-3) from the TROPHY-U-01 study and evaluated whether efficacy was associated with Trop-2 expression. PATIENTS AND METHODS: TROPHY-U-01 (NCT03547973) is an open-label phase II study that assessed the efficacy and safety of SG (alone or in combinations) in patients with unresectable locally advanced or metastatic UC (mUC). Archival tumor samples collected at enrollment for C1-3 were analyzed for Trop-2 membrane expression by considering histological scores (H-scores; scale 0-300) and the percentage of membrane positive tumor cells at low magnification (4×). The association of Trop-2 with clinical endpoints [objective response rate (ORR), progression-free survival (PFS), and overall survival (OS)] was evaluated. RESULTS: In C1-3, tissue was collected from 158 (82%) of 192 treated patients, and 146 (76%) had evaluable Trop-2 data. Trop-2 was highly expressed in tumor samples. The median [interquartile range (IQR)] Trop-2 H-score was 215 (180-246), and the median (IQR) percentage of membrane positive tumor cells was 91% (80-98). Trop-2 expression at any level was observed in 98% of patients. Furthermore, ORR, PFS, and OS benefits were observed across all Trop-2 expression levels. CONCLUSIONS: Trop-2 protein is highly expressed in UC, as confirmed by examining tumors from patients enrolled in the TROPHY-U-01 trial. The results indicate that SG demonstrates efficacy in mUC across Trop-2 expression levels.

Radiotherapy plus pembrolizumab for advanced urothelial carcinoma: results from the ARON-2 real-world study.

The addition of metastasis-directed radiotherapy (MDRT) to immunotherapy in patients with advanced urothelial carcinoma (aUC) has shown promising results. We report the real-world data from the ARON-2 study (NCT05290038) on the impact of conventional (CRT) or stereotactic body radiotherapy (SBRT) on the outcome of aUC patients receiving pembrolizumab after platinum-based-chemotherapy. Medical records of 837 patients were reviewed from 60 institutions in 20 countries. Two hundred and sixty-two patients (31%) received radiotherapy (cohort A), of whom 193 (23%) received CRT and 69 (8%) received SBRT. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. With a median follow-up of 22.7 months, the median OS was 10.2 months, 6.8 months and 16.0 months in no RT, CRT and SBRT subgroups (p = 0.005), with an 1y-OS rates of 47%, 34% and 61%, respectively (p < 0.001). The 1y-OS rate in the SBRT subgroup were significantly higher for both lower (63%) and upper tract UC (68%), for pure urothelial histology (63%) and variant histologies (58%), and for patients with bone (40%) and lymph-node metastases (61%). Median PFS was 4.8 months, 9.6 months and 5.8 months in the CRT, SBRT and no RT subgroups, respectively (p = 0.060). The 1y-PFS rate was significantly higher (48%) in the SBRT population and was confirmed in all patient subsets. The difference in terms of ORR was in favour of SBRT. Our real-world analysis showed that the use of SBRT/pembrolizumab combination may play a role in a subset of aUC patients to increase disease control and possibly overall survival.

Enfortumab Vedotin for Elderly Advanced Urothelial Carcinoma Patients or Those With a Poor Performance Status.

BACKGROUND/AIM: The efficacy, safety, and liver toxicity of enfortumab vedotin (EV) for elderly advanced urothelial carcinoma (UC) patients and patients with a poor performance status (PS) are unclear. PATIENTS AND METHODS: We retrospectively analyzed the efficacy, safety, and liver toxicity of EV in elderly patients and patients with a poor PS between December 2021 and August 2023. RESULTS: Sixty-two patients (≥75 years old, n=22; PS≥2, n=10) were enrolled. Patients with PS≥2 had significantly lower albumin levels than those with PS<2 (p=0.023). The objective response and disease control rates did not differ significantly between patients <75 and ≥75 years old (p=0.598 and p=0.769, respectively) or between those with PS<2 and PS≥2 (p>0.99 and p=0.178, respectively). Progression-free survival (PFS) and overall survival (OS) were not significantly different in patients <75 years and ≥75 years (p=0984, 0.368). A significant difference in PFS (p=0.047) but not OS (p=0.086) was observed between the PS<2 and PS≥2 groups. The rates of any-grade and severe (grade ≥3) adverse events did not differ significantly between patients <75 and ≥75 years (p=0.471, p=0.136) or between PS<2 and PS≥2 groups (p>0.99, 0.99). Aspartate aminotransferase (AST) levels significantly increased, but alanine aminotransferase levels did not, following EV treatment (p<0.001). Multivariate analyses revealed that the albumin level was an independent prognostic factor (hazard ratio=0.159; p<0.001). CONCLUSION: EV demonstrated similar efficacy and safety in elderly and younger patients with advanced UC. In patients with a poor PS, although the safety was similar, survival was significantly worse in terms of PFS, while the AST levels were significantly elevated.

Clinical Outcomes of Enfortumab Vedotin in Advanced Urothelial Carcinoma With Prior Avelumab Versus Pembrolizumab Therapy.

BACKGROUND/AIM: This study retrospectively evaluated whether enfortumab vedotin (EV) monotherapy is effective as a late-line treatment according to prior treatment type in patients with advanced urothelial carcinoma (UC). PATIENTS AND METHODS: We assessed consecutive patients from the Uro-Oncology Group in the Kyushu study population with lower and upper urinary tract cancer treated with EV monotherapy after platinum-based chemotherapy and immune checkpoint inhibitor therapy failure between December 2021 and March 2024. In particular, patients receiving avelumab maintenance or pembrolizumab therapy before EV for advanced UC were analyzed and compared according to the response rate, progression-free survival (PFS), and overall survival (OS). RESULTS: Of the 80 enrolled patients, 31 and 49 received avelumab and pembrolizumab before EV therapy, respectively. The avelumab and pembrolizumab groups had comparable objective response rates (48.4% vs. 44.9%, p=0.820) and disease control rates (77.4% vs. 67.3%, p=0.448). These two groups showed no significant difference in PFS from the initiation of EV (median: 6.4 months vs. 4.2 months, p=0.184); meanwhile, the avelumab group had better OS from the initiation of EV than the pembrolizumab group (median: 16.0 months vs. 10.2 months, p=0.019). Moreover, the median OS after first-line chemotherapy initiation was longer in the avelumab group than in the pembrolizumab group (40.3 months vs. 24.7 months, p=0.054). On multivariate analysis, avelumab maintenance therapy before EV reduced the mortality risk by 47% (95% confidence interval=0.27-1.03; p=0.059). CONCLUSION: EV monotherapy after avelumab maintenance therapy provides favorable survival outcomes in patients with advanced UC.

A Podcast on Practical Considerations in Patients with Advanced Urothelial Cancer Receiving First-Line Cisplatin- or Carboplatin-Based Chemotherapy Followed by Avelumab Maintenance in a Changing Therapeutic Landscape.

Platinum-based chemotherapy has been the cornerstone of first-line treatment for advanced urothelial carcinoma for decades, based on its proven efficacy and well-characterized safety profile. Although enfortumab vedotin (EV) plus pembrolizumab showed superior efficacy versus platinum-based chemotherapy in the EV-302 phase 3 trial, common and potentially cumulative toxicities associated with EV plus pembrolizumab may make this combination less suitable for some patients, such as those with pre-existing neuropathy, hyperglycemia, or hepatic impairment, or patients likely to have favorable outcomes with platinum-based chemotherapy. The availability of EV plus pembrolizumab in various countries may also be limited by financial considerations. Thus, platinum-based chemotherapy is likely to remain a valuable option for advanced urothelial carcinoma. Eligibility for cisplatin- or carboplatin-based regimens can be determined by assessing renal function, performance status, and specific comorbidities. In cisplatin-eligible and -ineligible patients without disease progression following platinum-based chemotherapy, avelumab first-line maintenance is standard of care based on findings from the JAVELIN Bladder 100 phase 3 trial, which showed that avelumab first-line maintenance plus best supportive care prolonged overall survival and progression-free survival compared with best supportive care alone across clinically relevant subgroups. Adverse events associated with avelumab were generally consistent with those observed with other immune checkpoint inhibitors, and long-term follow-up showed no new safety concerns with prolonged treatment. Efficacy benefits and safety profiles were similar in patients who received avelumab first-line maintenance after cisplatin- or carboplatin-based chemotherapy. The effectiveness and safety of avelumab first-line maintenance have been confirmed in several real-world studies. Overall, these data support the use of avelumab first-line maintenance for all platinum-treated patients without disease progression. In this podcast, we discuss the evolving role of platinum-based chemotherapy in this disease setting in the context of EV-302 trial results and describe practical considerations in patients receiving first-line cisplatin- or carboplatin-based chemotherapy followed by avelumab maintenance therapy.

Urological cancer statistics on incidence from 1975 to 2019 and mortality from 1958 to 2022 in Japan.

BACKGROUND: In Japan, comprehensive cancer statistics are collected through cancer registries. However, data on urological cancers are rarely summarized or published in research papers. METHODS: This retrospective study was performed using publicly available statistical data on urological cancers (prostate cancer [PCa], bladder cancer [BCa], and cancers of kidney and urinary tract [except urinary bladder]) in Japan, including a summary of the Ministry's mortality statistics, cancer incidence statistics from the Regional Cancer Registries through 2015, and the National Cancer Registry statistics from 2016. We examined the incidence and mortality rates of urological cancers stratified by age groups. RESULTS: The number of new cases of PCa, BCa, and cancers of kidney and urinary tract (except urinary bladder) in 2019 was 94,748, 23,383, and 30,458, respectively, and the number of deaths in 2022 was 13,439, 9,598, and 9,795, respectively. The incidence and mortality rates of urological cancers have consistently increased. Since 2000, there has been a noteworthy increase in the mortality rate of urological cancers among individuals aged > 85 years. The incidence and mortality rates of BCa and cancers of kidney and urinary tract (except urinary bladder) were significantly higher in males than in females. CONCLUSIONS: Urological cancers in very elderly patients (> 85 years) will become increasingly important in the future.

Dose-response relationship between arsenic in drinking water and mortality of urinary cancers in Taiwan.

Ingested arsenic is carcinogenic to the human urinary tract, but uncertainties remain regarding the dose-response relationship. To assess dose-response relationships between arsenic ingestion and urinary cancers, we evaluated the associations between the arsenic level in drinking water and mortality of cancers of the bladder, kidney, and prostate in Taiwan. We utilized the 1971-2000 Taiwan death registry data and calculated the age-standardized mortality rates (ASMRs) using the 1976 world standard population as the reference group. We used the data from a 1974-1976 census survey of wells on the arsenic levels in drinking water conducted by the government to assess exposure levels, which had been divided into three categories: below 0.05 ppm, 0.05-0.35 ppm, and above 0.35 ppm. The data were analyzed using multiple linear regression models and geographical information system. We found no increase in ASMR for all, or any, of the urinary cancers at exposure levels of 0.05-0.35 ppm arsenic, but at exposure levels > 0.35 ppm arsenic was associated with increased ASMR in both males and females for bladder cancer, kidney cancer, and all urinary cancers combined. There was no increased ASMR associated with prostate cancer observed for either exposure category.

Impact of baseline body composition on prognostic outcomes in urological malignancies treated with immunotherapy: a pooled analysis of 10 retrospective studies.

OBJECTIVE: Numerous epidemiological investigations have explored the impact of body composition on the effectiveness of immune checkpoint inhibitors (ICIs) in urological malignancies (UM) patients, yielding conflicting findings. As a result, our study aims to elucidate the influence of baseline body composition on the long-term prognosis of UM patients treated with ICIs. METHODS: We employed a rigorous systematic search across various databases, including PubMed, Embase, the Cochrane Library, and Google Scholar, to identify studies meeting our inclusion criteria. Our primary endpoints of interest encompassed overall survival (OS) and progression-free survival (PFS). RESULTS: This analysis included a total of 10 articles with a combined patient cohort of 707 individuals. Our findings revealed a noteworthy association between several body composition parameters and unfavorable OS outcomes, including low psoas muscle index (PMI; HR: 3.88, p < 0.001), low skeletal muscle index (SMI; HR: 1.63, p < 0.001), sarcopenia (HR: 1.88, p < 0.001), low visceral adipose index (VAI; HR: 1.38, p = 0.018) and low subcutaneous adipose index (SAI; HR: 1.37, p = 0.018). Furthermore, our analysis demonstrated that low PMI (HR: 2.05, p = 0.006), low SMI (HR: 1.89, p = 0.002), sarcopenia (HR: 1.80, p < 0.001), and low VAI (HR:1.59, p = 0.005) were significantly correlated with inferior PFS. Conversely, SAI did not manifest a pronounced association with PFS in UM patients treated with ICIs. CONCLUSION: Collectively, our study findings underscore a substantial relationship between baseline body composition and reduced clinical efficacy in UM patients undergoing ICI therapy.

Gustave Roussy Immune score as a prognostic biomarker in patients with platinum-refractory metastatic urothelial carcinoma treated with pembrolizumab: YUSHIMA study.

BACKGROUND: This study aimed to investigate the prognostic value of the Gustave Roussy Immune score (GRIm-score) in platinum-refractory metastatic urothelial carcinoma (UC) treated with pembrolizumab. METHODS: This multicenter retrospective study (YUSHIMA study) evaluated 331 patients with metastatic UC treated with pembrolizumab after platinum-based chemotherapy between January 2018 and June 2023 at 13 institutions. We collected pretreatment variables, including the GRIm-score based on serum albumin, lactate dehydrogenase, and neutrophil-to-lymphocyte ratio. The patients were divided into low and high GRIm-score groups. Prognostic factors for overall survival (OS) and progression-free survival (PFS) were determined using the multivariate Cox proportional hazard model. RESULTS: During the median follow-up period of 7.3 months, 278 (84%) patients showed disease progression, and 223 (67%) died from any cause. Multivariate analysis revealed that the high GRIm-score group was an independent and significant adverse prognostic factor of both OS and PFS (hazard ratio, 1.65 and 1.82, respectively; both p < 0.001) along with Eastern Cooperative Oncology Group Performance Status of ≥ 2 (both p < 0.001), presence of visceral metastasis (both p < 0.001), and hemoglobin of < 9.2 g/dL (p = 0.030 and p = 0.038). C-reactive protein of > 42 mg/L was a significant prognostic factor for OS (p = 0.001). CONCLUSION: The GRIm-score is an independent prognostic marker for survival outcomes in patients with platinum-refractory metastatic UC treated with pembrolizumab.

Teaching Hospitals and Textbook Outcomes After Major Urologic Cancer Surgery.

OBJECTIVE: To assess textbook outcomes by hospital teaching status following major surgery for urologic cancers. METHODS: We used 100% national Medicare Provider Analysis and Review files from 2017-2020 to assess rates of textbook outcomes in patients undergoing bladder (ie, radical cystectomy), kidney (ie, radical or partial nephrectomy), and prostate (ie, radical prostatectomy) surgery for genitourinary malignancies. The extent of integration of learners into each hospital's workforce-defined as major, minor, and non teaching hospitals-was the primary exposure. A textbook outcome, measured at the patient level, was defined as the absence of in-hospital mortality and mortality within 30days of surgery, no readmission 30days following discharge, no postoperative complication, and no prolonged length of stay. RESULTS: Textbook outcomes were achieved in 51% (8564/16,786) of patients after bladder cancer surgery, 70% (39,938/57,300) of patients after kidney cancer surgery, and 82% (50,408/61,385) of patients after prostate cancer surgery. After adjusting for patient- and hospital-level characteristics, teaching hospitals had higher rates of textbook outcomes in those undergoing bladder (50.7% vs 44.0%; P = .001), kidney (72.0% vs 69.7%; P = .02), and prostate (85.3% vs 81.0%; P <.001) surgery. This effect was attenuated, but not eliminated, by surgical volume in additional sensitivity analyses for bladder (OR: 1.20, 95% CI: 1.00-1.42; P = .04) and prostate (OR: 1.15, 95% CI: 1.00-1.32; P = .04) surgery. There were no significant differences in kidney cancer surgery outcomes after adjusting for hospital volume (OR: 1.03, 95% CI: 0.93-1.14; P = .6). CONCLUSION: Undergoing major cancer surgery at a teaching hospital was associated with an increased likelihood of achieving a textbook outcome. This effect was attenuated by volume but persisted for bladder and prostate surgery.

C-reactive Protein Is a Prognostic Factor for Survival in Metastatic Upper Tract Urothelial Carcinoma Patients Receiving Pembrolizumab.

BACKGROUND/AIM: The number of available treatment options for urothelial carcinoma has increased recently. Upper tract urothelial carcinoma (UTUC) is relatively rare compared with bladder cancer. There are few reports on the efficacy of immune checkpoint inhibitors (ICIs) for metastatic UTUC, and ICIs may occasionally show less efficacy and cause severe side effects. Therefore, it is important to predict the treatment response and change the treatment strategy as appropriate. We investigated the prognostic factors for treatment response in patients with metastatic UTUC treated with pembrolizumab at our hospital. PATIENTS AND METHODS: Patients who received pembrolizumab for UTUC between January 2018 and June 2023 were analyzed. Patients who presented with bladder cancer complications at initial diagnosis were excluded. The primary endpoints assessed were overall survival (OS) and progression-free survival (PFS). Statistical analyses were conducted using laboratory values obtained before and after pembrolizumab administration. The relationship between cancer and inflammation is important. Therefore, we analyzed this relationship using prognostic factors for urothelial carcinoma as previously reported. Specifically, pretreatment C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), and NLR/albumin values were examined. RESULTS: Forty-seven patients were analyzed. The median PFS was 66 days (24-107 days), and the median OS was 164 days (13-314 days). A CRP level <1 before the first cycle was a useful factor in the multivariate analysis for both OS and PFS [OS: p=0.004, hazard ratio (HR)=3.244, 95% confidence interval (CI)=1.464-7.104; PFS: p=0.003, HR=2.998, 95%CI=1.444-6.225]. CONCLUSION: CRP level is a prognostic factor for pembrolizumab treatment response in patients with UTUC.