Clinical genitourinary cancer最新文献

Background and objective: Shared decision-making for localized prostate cancer (PCa) requires understanding how baseline factors predict patient-reported outcomes (PROs) after treatment. Most prior predictive models are limited by small, single-region cohorts. We sought to develop and evaluate models predicting 12-month PROs using the large, multi-national Movember True North Global Registry (TNGR).

Methods: We identified 27,499 men with localized PCa across 15 countries (2016-2022). Patients were randomly split into training (n = 18,332) and validation (n = 9,167) cohorts. Multivariable linear regressions incorporated baseline PROs, demographics, country, primary treatment (active surveillance, radical prostatectomy, external-beam radiotherapy ± androgen-deprivation therapy, or brachytherapy), and tumor characteristics (grade, stage, percent positive biopsy cores, PSA). Outcomes were changes from baseline to 12 months across 5 EPIC-26 domains.

Results: Baseline function, treatment modality, and tumor features were associated with 12-month changes across domains. When applied to the validation cohort, model performance explained 15%, 14%, 19%, 32%, and 28% of variance in urinary incontinence, irritative urinary, bowel, sexual, and hormonal function, respectively.

Conclusions: In this first global analysis of functional outcomes after PCa treatment, predictive accuracy was modest, reflecting substantial regional and practice heterogeneity. These findings underscore both the limits of universal prediction models and the value of large-scale international data for benchmarking outcomes. Future TNGR work will focus on region-specific and locally calibrated models to support more personalized counseling and quality-improvement initiatives.

Introduction: Cisplatin-based chemotherapy (CBCT) is standard treatment for most men with metastatic testicular cancer (TC). The main objective was to evaluate changes in physical fitness and body composition from before to immediately after CBCT and 3 months after completion of CBCT.

Patients and materials: The assessments included cardiorespiratory fitness (peak oxygen uptake [VO₂ peak]), muscle strength (1 repetition maximum [1RM]) and muscular endurance in leg- and chest press, body composition (dual-energy X-ray absorptiometry), physical activity (PA) levels, and patient-reported outcomes (functional scales, global quality of life [QoL], mental health and fatigue). Twenty-eight patients were included, most with low-volume metastatic disease and all within the good prognosis risk group.

Results: From before the start of CBCT to immediately after the last CBCT cycle, there were significant reductions in VO₂ peak by 24% (P < .001), 1RM leg press by 8% (P = .004), 1RM chest press by 17% (P = .001), chest press endurance by 22% (P = .005), total lean body mass by 2.2 kg (P < .001), PA level, physical-, role-, cognitive- and social functioning, and QoL; and significant increases in total and physical fatigue and symptoms of depression. There was a good correlation between reductions in VO₂ peak and QoL during CBCT (r = 0.54, P = .016), whereas no correlation between reductions in VO₂ peak and PA levels. Twelve weeks after CBCT, all variables had returned to baseline values except for PA levels and physical functioning.

Conclusion: TC patients should be prepared for reductions in physical fitness and QoL during CBCT. The reduction in cardiovascular fitness is possibly independent of the PA level.

Background: Bone metastases occur in one third of patients with metastatic clear cell renal cell carcinoma (mccRCC) and are associated with poor prognosis. Optimal first-line treatment for this subgroup of patients remains undefined.

Methods: We conducted a multicenter retrospective study of patients with bone-metastatic (BM+) mccRCC treated with first-line immune checkpoint inhibitor (ICI)-based combinations between January 2015 and February 2024 across 8 French centers. The primary endpoint was time to next treatment (TTNT). Secondary endpoints included overall survival (OS), bone progression-free survival (bPFS), incidence of skeletal-related events (SREs) and changes in bone pain.

Results: A total of 124 patients were included; 55% received ICI-ICI and 45% an ICI plus a tyrosine kinase inhibitor (TKI). Median follow-up was 36.8 months. Median TTNT was 11.7 months (95% CI, 8.38-20.0), OS 28.8 months (95% CI, 23.7-40.2) and bPFS 11.7 months (95% CI, 7.69-21.7). Median TTNT was numerically longer with ICI-TKI compared to ICI-ICI (17.9 vs. 8.5 months; P = .40), with no significant difference in OS or bPFS between treatment groups. SREs occurred in 32% of patients. Bone progression was observed in 48%, with a concomitant SRE in 54% mostly involving preexisting lesions (78%). Bone pain improved in 45% of evaluable patients. No significant differences were observed between treatment groups for SRE incidence or bone pain improvement. Hypercalcemia was associated with shorter OS and bPFS, while bone-only disease correlated with improved OS. Use of bone-targeting agents (BTAs) was independently associated with longer bPFS.

Conclusion: ICI-CI and ICI-TKI combinations showed comparable outcomes in BM+ mccRCC. Bone progression and SREs remained frequent and often involved preexisting bone lesions. These findings support early integration of local treatments as well as BTAs, which were independently associated with longer bPFS.

Introduction: Enfortumab vedotin (EV)-based regimens have become standard treatments for advanced urothelial carcinoma (aUC). However, clinical trials excluded clinically significant peripheral neuropathy or uncontrolled diabetes mellitus. Therefore, we characterized real-world outcomes of patients with aUC and pre-existing peripheral neuropathy and/or diabetes mellitus receiving EV-based therapies.

Patients and methods: In the multicenter retrospective UNITE database, patients with documented baseline neuropathy and diabetes mellitus were identified. Observed response rate (ORR) and duration of response (DOR) were compared using Fisher's exact test. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. Multivariable Cox models were used to adjust for confounding variables, including treatment duration.

Results: Comparing 268 patients with baseline neuropathy to 586 patients without neuropathy, median PFS was 7.2 versus 6.3 months (HR 0.87 [0.73-1.04]; P = .11), and median OS 14.4 versus 13.0 months (HR 0.88 [0.73-1.07]; P = .21), Although discontinuation rate due to intolerance was significantly higher for patients with baseline neuropathy (26% vs. 18%; P = .008), these patients did not have shorter survival. Comparing 157 patients with baseline diabetes mellitus to 697 patients without diabetes mellitus, median PFS was 5.3 versus 6.7 months (HR 1.24 [1.01-1.52]; P = .04), and median OS 13.7 versus 13.3 months (HR 1.06 [0.84-1.34]; P = .62).

Conclusion: Patients with known baseline neuropathy and/or diabetes mellitus did not have worse survival outcomes receiving EV-based regimens. Patients with baseline neuropathy who discontinued EV early due to intolerance also did not exhibit worse survival. Our findings suggest despite these relevant underlying comorbidities, patients with aUC can derive benefit from EV-containing regimens, with very close monitoring.

Introduction: Belzutifan, a HIF-2α inhibitor, represents a new therapeutic option for patients with advanced clear-cell renal cell carcinoma (ccRCC); however, data regarding optimal postprogression treatment strategies is limited. With an expanding role of HIF-2α inhibitors, this study aimed to assess the activity of targeted therapies (TT) following belzutifan failure.

Methods: We conducted a multicenter retrospective study including patients with ccRCC treated with belzutifan-based regimens who subsequently received further TT. The primary endpoint were time to treatment failure (TTF) and objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), and overall survival (OS).

Results: Thirty-five patients were included. Most (79%) received vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) after belzutifan, primarily in the third-line setting or beyond. The most frequently used agents were cabozantinib (46%), axitinib (29%), and everolimus (14%), the latter representing a mechanistically distinct agent as a mammalian target of rapamycin (mTOR) inhibitor. The median TTF for subsequent TT was 6.13 months (mo) (95% CI, 3.44-11.28). ORR was 20% and a median PFS was 6.13 mo (95% CI, 5.02-12.2). The median OS was 11.28 mo (95% CI, 6.89-NR), with a 1-year survival rate of 49% (95% CI = 31-65).

Conclusions: Despite extensive prior treatment, patients experienced clinical benefit from TT, particularly VEGFR-TKIs, after progression on belzutifan. These findings support the feasibility of sequencing TT following belzutifan-based regimens in advanced ccRCC, and highlight the need to further define optimal therapeutic sequencing strategies.

Background: Despite the efficacy of Lutetium-177 (¹⁷⁷Lu)-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer (mCRPC), high discontinuation rates limit its therapeutic potential. This study aimed to characterize discontinuation reasons, timing, predictive factors, and survival impact in a real-world cohort.

Methods: We retrospectively analyzed 208 mCRPC patients treated with ¹⁷⁷Lu-PSMA-617 between 2017 and 2024. Discontinuation was defined as cessation before 6 cycles. Reasons were categorized as disease progression, serious adverse events, patient-related factors, physician decision, death, or miscellaneous. Early discontinuation was defined as < 3 cycles. Logistic regression and Cox models identified predictors of discontinuation and overall survival (OS).

Results: Median cycles received were 3 (IQR 2-5); 169 patients (81.2%) discontinued, with 92 (44.2%) early discontinuation. Disease progression (43.8%) and serious adverse events (21.9%) were leading causes. Multivariate analysis revealed baseline creatinine (OR 5.50, P = .050) and ALP (per 100 U/L; OR 1.12, P = .032) predicted overall discontinuation, while Gleason score (OR 2.11, P = .009), hemoglobin (OR 0.62, P < .001), and platelet counts (OR 0.54, P = .004) predicted early discontinuation. Median OS was 13 months overall, 11 months in discontinuers versus 22 months in completers (P < .001), and 5 vs. 20 months in early vs. nonearly groups (P < .001). Treatment discontinuation (HR 1.95, P = .001) and hemoglobin (HR 0.68, P < .001) independently predicted OS.

Conclusion: Over 80% of mCRPC patients discontinued ¹⁷⁷Lu-PSMA-617, driven by progression and toxicity, with early discontinuation linked to aggressive disease and poor hematologic reserve. Discontinuation independently worsens survival, emphasizing the need for careful selection and supportive interventions to improve adherence and outcomes.

Locally advanced or metastatic penile cancer (LA/mPC) is an aggressive and rare malignancy with limited treatment options. While promising, the role of Immune Checkpoint Blockade (ICB) in LA/mPC remains controversial. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of ICB in patients with LA/mPC. A literature search was conducted in PubMed, Embase, and Cochrane (up to June 2025). The analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines (CRD420251070583). Proportional outcomes were pooled using a random-effects proportional meta-analysis, and hazard ratios (HR) were pooled using a random-effects model. We used the available Kaplan-Meier curves to recreate time-to-event data from the studies considered. Heterogeneity between studies was evaluated using the I² metric and Cochran's Q test. A total of 12 cohorts (488 patients) were included in the analysis. The pooled Objective Response Rate in patients treated with ICB was 34.13% (95% CI, 20.62%-56.48%). Subgroup analysis demonstrated marked variability by treatment strategy, with an ORR of 60.7% for ICB plus chemotherapy versus 16.7% for ICB monotherapy (P < .01). At 12 months, pooled Progression-Free Survival (PFS) and Overall Survival (OS) rates were 62.64% (95% CI, 55.55%-70.63%) and 80.21% (95% CI, 74.11%-86.83%), respectively. The median PFS and OS were 5.7 months and 13.6 months, respectively. The pooled incidence of Immune-related Adverse Events was 40.36% (95% CI, 26.82%-60.74%) for any grade and 13.79% (95% CI, 7.67%-24.80%) for grade ≥ 3 events. ICB, particularly when combined with chemotherapy, shows signals of clinical activity in LA/mPC. However, due to high inter-study variability and the single-arm nature of the analysis, these findings are hypothesis-generating and require prospective, randomized, biomarker-driven validation.

Background: Immune checkpoint inhibitors (ICI) are commonly used in urothelial carcinoma. We sought to understand provider preferences for subsequent treatment of patients after prior ICI.

Materials and methods: We comprised a group of 11 expert genitourinary medical oncologists in the United States and created a survey regarding treatment sequencing. We present the final responses to this survey, using descriptive statistics.

Results: We received 78 responses (34%) from 227 genitourinary oncologists between May and August 2024; most were practicing for >5 years (62%) and were seeing >25 patients with metastatic urothelial carcinoma (mUC) yearly (72%). For patients with progression while receiving adjuvant ICI, 51% of respondents were somewhat/very likely to use enfortumab vedotin/pembrolizumab (EVP) as next therapy line. For patients with progression after prior ICI, 1/3 of respondents would consider first-line (1L) EVP irrespective of the interval from prior ICI completion. For ICI given in nonmuscle invasive bladder cancer and muscle-invasive bladder cancer, 43% and 45%, respectively would consider EVP > 6 months post-ICI completion. After progression on EVP, 77% were somewhat/very likely to give platinum-based chemotherapy, and most would not include combination or switch maintenance ICI. Similarly, 80% were somewhat/very likely to recommend non-ICI clinical trials in the second-line setting after EVP, and 87% were somewhat/very likely to offer erdafitinib for susceptible FGFR3 alterations.

Conclusion: Survey-based opinions can effectively capture treatment selection preferences for mUC and could inform future clinical trial design. Additional data, including the impact of residual toxicity from 1L EVP, are needed to better understand real-world treatment sequencing patterns.

Purpose: The aim of this study is to determine the incidence of prostate cancer (PC) and its trends according to the age, Gleason grade (GG) and stage.

Methods: Population-based study of PC cases diagnosed in Girona, Spain, from 2010 to 2021. Age at diagnosis, date and method of diagnosis, histology, Gleason score, and stage at diagnosis were collected. Poisson and negative binomial generalized linear models were used to estimate incidence trends and incidence rate ratios (IRRs), respectively.

Results: Five thousand three hundred nine cases were included, with a median age of 70 years (IQR:64-77). The age standardized rates according to GG ranged from 12.8 cases per 100,000 men-year (m-y) for GG 5 to 36.6 cases for GG 2 and from 19.9 to 52.6 cases per 100,000 m-y for stages IV and II, respectively. Overall, there was a decline between 2010 and 2014, with an annual percentage change (APC) of -6.1% (95% CI, -9.0, -3.1), followed by stabilisation (APC: -0.3% [95% CI, -2.1, 1.5]). Adjusted IRRs for GG 3, 4, and 5 were lower than GG 1 and IRRs for stages III and IV were lower than stage I; however, the IRR for stage II was higher (IRR = 1.53 [95% CI, 1.40, 1.67]).

Conclusions: Although the overall incidence of PC has remained stable since 2014, there has been an increase in cases with the worst prognosis. These cases usually involve elderly patients, who are the most vulnerable.