INTRODUCTION:It is unknown whether marital status affects years of life lost (YLL) in metastatic urothelial carcinoma of the urinary bladder (mUCUB), according to sex and race/ethnicity. METHODS:Within SEER database (2004-2021), unmarried and married mUCUB patients aged 40-80 years were identified. Age- and sex-matched controls were generated (Social Security Administration life tables and Monte Carlo simulation). Years of life lost (YLL) were quantified, relative to age- and sex-matched simulated population controls. RESULTS:In unmarried male mUCUB patients (n = 1,976), the distribution according to race/ethnicity was as follows: 1,546 Caucasians, 248 African Americans, 182 Hispanics. In unmarried female mUCUB patients (n = 998), the distribution according to race/ethnicity was as follows: 723 Caucasians, 161 African Americans, 114 Hispanics. In male mUCUB patients, unmarried status was more common in African Americans (OR 1.3, P < 0.05). YLL values in unmarried vs. married males relative to age- and sex- matched controls were 8.2 vs. 5.3 (Δ = 2.9) in Caucasians, 10.1 vs. 6.7 (Δ = 3.4) in African Americans and 8.2 vs. 7.3 (Δ = 0.9) in Hispanics. In Caucasian and African American mUCUB males, unmarried status independently predicted 1.2- fold higher CSM, but not in Hispanics. Conversely, unmarried status did not affect YLL values in females. CONCLUSION:In males mUCUB patients, African American race/ethnicity predisposes to unmarried status. Caucasian and African American unmarried mUCUB males exhibited higher YLL values than controls. In those two groups, unmarried status independently predicts higher CSM. Conversely, in females no meaningful differences in YLL were recorded according to marital status.
INTRODUCTION:The NIAGARA trial demonstrated improved event-free survival (EFS) with perioperative durvalumab plus gemcitabine-cisplatin (GC) vs. GC alone in muscle-invasive bladder cancer (MIBC). This analysis applied mixture cure models to explore whether this EFS benefit may reflect an increase in the proportion of patients achieving long-term event-free status, complementing standard hazard ratio analyses. METHODS:Reconstructed individual patient data (rIPD) were derived from published Kaplan-Meier curves. Parametric mixture cure models (Weibull, log-logistic, and log-normal) were fitted separately by treatment arm, with model selection based on the Akaike Information Criterion (AIC). Cure regression models decomposed treatment effects into cure and latency components. Sensitivity analyses assessed robustness to reconstruction uncertainty and follow-up duration. RESULTS:The rIPD reproduced the published trial results with reasonable concordance (hazard ratio 0.68 vs. reported 0.68). The log-normal model provided the best fit. The estimated cure fraction (π) was 41% (95% confidence interval [CI]: 32%-48%) for the control arm and 60% (95% CI: 55%-65%) for the durvalumab arm, yielding a model-based difference (Δπ) of +19 percentage points (pp) (95% CI: +10 to +29). Akaike weights favored a cure-effect-only model (71%) over a combined cure-plus-latency model (29%), with a latency-only model receiving negligible support (<1%). Perturbation sensitivity analyses indicated that these bootstrap intervals underestimate total uncertainty, with individual-run estimates spanning negative values at plausible reconstruction noise levels. CONCLUSIONS:In this exploratory analysis of reconstructed individual patient data, perioperative durvalumab was associated with an estimated +19 pp higher cure fraction (95% CI: +10 to +29); cure regression assigned an Akaike weight of 71% to a pure cure fraction mechanism vs. 29% to a combined cure-plus-latency mechanism. These estimates depend on the reconstructed dataset and on the assumption that the EFS curves have plateaued within the observed follow-up; perturbation sensitivity analyses indicated that at plausible reconstruction noise (SD ≥ 0.5 months) the range of individual-run estimates spans negative values.
Nectin‑4, a cell adhesion molecule and emerging therapeutic target in several malignancies, has not been fully characterized in renal cell carcinoma (RCC). This study aimed to define the clinical significance, biological function, and therapeutic implications of Nectin‑4 across RCC subtypes. Immunohistochemistry of 273 primary RCC samples revealed that the expression of Nectin‑4, although present in a minority of clear cell RCC (ccRCC) cases, was significantly enriched in nonclear cell RCC (nccRCC). Nectin‑4 positivity was correlated with adverse pathological features, including higher pT stage, tumor grade, and venous invasion. In ccRCC, the expression of Nectin‑4 was associated with inferior overall survival, consistent with the findings from a public dataset analysis. In vitro experiments demonstrated that Nectin‑4 overexpression enhanced the proliferation and invasion of multiple RCC cell lines, supporting a tumor‑promoting role. Transcriptomic analyses across TCGA‑KIRC, TCGA‑KIRP, JAVELIN Renal 101, and CheckMate‑025 cohorts showed that the high expression of NECTIN4 was strongly associated with epithelial-mesenchymal transition, inflammatory signaling, sarcomatoid features, and genomic dedifferentiation. Despite these aggressive biological features, the expression of NECTIN4 was not correlated with immune infiltration markers and did not predict the clinical benefit of immune checkpoint inhibitors. These findings suggest that Nectin‑4 is a marker of tumor aggressiveness and dedifferentiation, rather than an immunotherapy biomarker. Given its relatively high expression in nccRCC and its functional contribution to malignant behavior, Nectin‑4-directed antibody-drug conjugates may represent a promising therapeutic option for this underserved population and warrant further investigation.
Patient-reported outcome measures are increasingly used to assess symptoms, treatment tolerance, and quality of life (QoL) in oncology. Electronic patient-reported outcome measures (ePROM) offer advantages over paper questionnaires, but large-scale evidence using smartphone text messaging in clinical trials is limited. To evaluate the feasibility of collecting ePROM via smartphone text messages in a large-scale, multinational randomized controlled trial of patients receiving Bacillus Calmette-Guérin therapy for non-muscle-invasive bladder cancer. This methodological study was embedded in the North-REG Dwell Time study. During each instillation week, participants received a daily text message linking to a questionnaire assessing side effects. Four additional QoL questionnaires were distributed during the 1-year study period. Non-responders received 2 automated reminders. Patients were randomized into an intervention and control group that differed only in dwell time. All responses were transferred directly into a trial database. Feasibility was assessed by calculating overall response rates and separate response rates for daily side-effect and QoL questionnaires. Between February 2021 and November 2024, 242 participants were enrolled and 225 received at least one instillation. A total of 24,286 text messages were sent, corresponding to 15,485 initially activated questionnaires. The overall response rate was 95%. Response rates were 95% for daily side-effect questionnaires and 87% for QoL questionnaires. No significant differences were found between the intervention and control groups, regarding response rates. Smartphone text messaging is highly feasible for collecting ePROM in a multinational bladder cancer trial, yielding excellent response rates and enabling near real-time symptom monitoring with minimal recall bias.
OBJECTIVES:To evaluate whether exposure to glucagon-like peptide-1 receptor agonists (GLP-1) or sodium-glucose cotransporter 2 inhibitors (SGLT2) is associated with overall survival (OS) in adults with treated bladder cancer. SUBJECTS/PATIENTS AND METHODS:We conducted a retrospective cohort study using de-identified electronic health records from the TriNetX Global Collaborative Network (2013-2024). Adults with bladder cancer receiving surgery, chemotherapy, and/or radiotherapy were classified as GLP-1 receptor agonist- or SGLT2 inhibitor-exposed vs. nonexposed (mutual class exclusion). Treatment had to occur within ±3 months of the bladder cancer criterion for GLP-1 receptor agonist and within ±3 months for SGLT2 inhibitors. Exposed and nonexposed cohorts were propensity-score matched 1:1 on demographics, comorbidities, and concomitant medications. OS was assessed from day 1 through day 3650 after the index event. RESULTS:After matching, 5,294 GLP-1 receptor agonist users were compared with 5,294 nonusers, and 5,356 SGLT2 inhibitor users with 5,356 nonusers. Mortality was lower with GLP-1 receptor agonist exposure (934 vs. 1,855 deaths; hazard ratio for nonuse vs. use 1.915, 95% CI, 1.770-2.073; P < 0.001) and with SGLT2 inhibitor exposure (1,325 vs. 2,099 deaths; hazard ratio 1.232, 95% CI, 1.148-1.322; P < 0.001). In 6- and 12-month landmark sensitivity analyses the associations attenuated but remained statistically significant. CONCLUSION:In these large, propensity-matched, multicenter real-world cohorts of treated bladder cancer, GLP-1 receptor agonist and SGLT2 inhibitor exposure were each associated with improved OS. Limitations include residual confounding and limited granularity for tumor stage and treatment intent; prospective and mechanistic studies are needed to assess causality and clinical utility.
INTRODUCTION:Radical cystectomy with orthotopic urinary diversion is a standard treatment for muscle-invasive bladder cancer. However, the impact of different bowel segments used for neobladder reconstruction on postoperative quality of life and sexual function remains underexplored. This prospective randomized study compared the outcomes of orthotopic ileal neobladders (INB) and sigmoid neobladders following nerve-sparing, vas deferens-sparing, seminal vesicle-sparing, and partial prostate-sparing radical cystectomy. MATERIALS AND METHODS:Seventy-nine sexually active male patients with histopathologically confirmed T2 or high-grade T1 (T1G3) bladder cancer were randomized to INB (n = 38) or sigmoid neobladders (n = 41) reconstruction. All procedures were performed by a single urologist. Quality of life and sexual function were assessed using the European Organization for Research and Treatment of Cancer Quality-of-Life Core Questionnaire, version 3 and International Index of Erectile Function-15 (validated Hindi versions), respectively, preoperatively and at 1, 3, 6, 12, and 18 months postoperatively. Data were analyzed using SPSS version 23.0, and mean differences were calculated with 95% confidence intervals. RESULTS:Baseline demographic and pathological characteristics were comparable between groups. European Organization for Research and Treatment of Cancer Quality-of-Life Core Questionnaire, version 3 scores showed progressive improvement over time, with no significant difference in global health or overall functional recovery between INB and sigmoid neobladders groups at 18 months. However, International Index of Erectile Function-15 analysis revealed significantly better preservation of erectile function, orgasmic function, sexual desire, and intercourse satisfaction in the INB group, indicating superior early sexual rehabilitation. CONCLUSION:Both orthotopic neobladders provide comparable long-term quality of life outcomes. Nevertheless, the INB offers better postoperative sexual function recovery, supporting its preference in suitable male patients undergoing nerve-sparing radical cystectomy.
BACKGROUND:International Society of Uro-Pathology (ISUP) grade group 2 prostate cancer (GG2 PCa) with suspicion of extraprostatic extension (EPE) on preoperative multiparametric MRI (mpMRI) presents a paradox: an histologically favorable intermediate-risk tumor with aggressive imaging features. We aimed to characterize this population, and identify predictors of pathological upgrading, downstaging, and oncological outcomes after robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS:We analyzed data from 150 patients across 8 European centers with MRI-targeted biopsy-confirmed GG2 PCa and mpMRI-suspected EPE (icT3a), stratified by EPE score, who underwent RARP between 2019 and 2024. Primary endpoint was predictors of pathological upgrading (GG ≥ 3); secondary endpoints included downstaging (pT2), surgical margins, and biochemical recurrence (BCR)-free survival. RESULTS:Patients were divided by EPE score: low (1-2, n = 87) and high (3, n = 38). Pathological upgrading occurred in 36% (55/150), including 10% to GG 4-5. High EPE score was the only significant predictor. Conversely, 46% (69/150) were downstaged to pT2, with low EPE score as main predictor. Positive surgical margins were observed in 30% (45/150). At a median follow-up of 28 months (IQR 17-43), 5-year BCR-free survival was 67% (95% CI 53-85). Posterior/apical EPE on MRI and cT3a stage were linked to higher BCR risk. CONCLUSIONS:GG2 PCa with mpMRI-suspected EPE is heterogeneous, showing risks of both upgrading and organ-confined disease. EPE score was the main predictor of both. Despite imaging suspicion, RARP outcomes remained favorable.
BACKGROUND:Accurate detection of clinically significant prostate cancer (csPCa) is essential for treatment decisions. MRI-targeted biopsy improves accuracy but is limited by cost, availability, and inter-reader variability. Micro-ultrasound (microUS) is a high-resolution modality enabling real-time detection of suspicious lesions. OBJECTIVE:To compare the diagnostic accuracy of microUS-targeted biopsy plus systematic biopsy (microUS + SB) vs. MRI-targeted biopsy plus systematic biopsy (MRI + SB) using radical prostatectomy (RP) specimens as reference. METHODS:We retrospectively analyzed 142 patients undergoing perineal microUS-MRI fusion biopsy from January 2021 to July 2023 at Charité-Universitätsmedizin Berlin, followed by RP. Biopsy ISUP grades were compared with RP pathology per patient. CsCaP detection (ISUP ≥ 2) was evaluated with sensitivity, specificity, and AUC. Concordance was assessed using Wilcoxon signed-rank, Pearson Chi-Square, and McNemar-Bowker tests. RESULTS:MicroUS + SB was the only modality without significant deviation from RP ISUP grade (P = 0.065), whereas MRI + SB remained significantly different (P = 0.012). Sensitivity for csCaP was 73.3% for microUS + SB and 69.5% for MRI + SB, with similar positive predictive values (97.96% vs. 98.91%). AUCs were comparable (0.776 vs. 0.802). ISUP grading accuracy did not differ significantly (P = 0.127). No significant predictors of upgrading were identified, though a trend was seen for the number of positive microUS-targeted cores (P = 0.055). CONCLUSIONS:MicroUS + SB achieves comparable diagnostic accuracy to MRI + SB for csCaP. Its real-time imaging, cost-effectiveness, and accessibility make microUS a promising alternative to MRI. Prospective studies are warranted to confirm these findings.
BACKGROUND:Vessel invasion (VI) in transurethral resection of bladder tumor (TURBT) is associated with lymph node metastases and reduced survival. Separation of blood (BVI) and lymph (LVI) vessel invasion with immunohistochemistry (IHC) in cystectomy (RC) has indicated different prognosis and could guide treatment already at the time of TURBT. The prognostic impact of BVI and LVI at TURBT has not been elucidated. OBJECTIVE:To examine BVI and LVI separately in TURBT using IHC and investigate their value for predicting nodal metastases, extravesical disease, distant metastases and survival after RC. METHODS:We reviewed TURBT specimens from a retrospective, population-based series of 291 patients later treated with RC regarding VI on routine- stained sections (hematoxylin-eosin-saffron; VI-HES). One tumor block per case was stained using D2-40/CD31 antibodies for separate analysis of BVI and LVI. RESULTS:The frequency of LVI and BVI was 31% and 20%, and VI-HES 31%. BVI independently predicted extravesical disease at RC and distant metastases within 12 months. LVI and VI-HES predicted lymph node metastases. BVI showed reduced recurrence-free survival (RFS; hazard ratio (HR) 1.7, 95% confidence interval (CI) 1.0-2.7, P = 0.035) and disease-specific survival (DSS; HR 1.8, CI 1.1-2.9, P = 0.018) in multivariable analysis, whereas LVI was not significantly related to survival. VI-HES showed reduced DSS and marginal significance for reduced RFS. CONCLUSIONS:At TURBT, IHC improves detection of vessel invasion and differentiates BVI from LVI, enhancing risk stratification compared with VI-HES. Presence of BVI in TURBT specimens predicts distant metastases and reduced survival and should be incorporated in clinical decision-making.
INTRODUCTION:The criteria for active surveillance and focal therapy in Gleason score (GS) 3 + 4 disease remain unclear. We aimed to refine them by evaluating predictors of adverse pathology and low-volume disease at radical prostatectomy (RP). METHODS:We retrospectively analyzed 1,665 men with biopsy GS 3 + 4 disease who underwent RP. Associations of biochemical recurrence (>0.2 ng/ml) and three definitions of adverse pathology were evaluated using Cox models: (1) GS ≥4 + 3 or pT3a-4, (2) GS ≥4 + 3 or pT3b-4, and (3) GS ≥4 + 4 or pT3a-4. The definition with the highest C-index was selected as the primary endpoint. Preoperative clinicopathological and MRI predictors of the selected adverse pathology were identified using multivariable logistic regression. With the same predictors, tumor diameter and volume at RP were assessed. The low-risk criteria were defined as a ≤ 20% predicted risk of the selected adverse pathology. RESULTS:Definition 2 yielded the highest C-index (0.76; 95% CI, 0.71-0.81). Independent predictors were age, Black race, PSA, cT stage, maximum involvement of biopsy core (%), and MRI-detected extracapsular extension or seminal vesicle invasion. They were consistently associated with larger tumor diameter and volume, except for age and race. The low-risk criteria were defined as PSA ≤5 ng/ml, cT1 stage, absence of extracapsular extension or seminal vesicle invasion, and cancer involvement ≤30% of any core. The limitation was surgical selection bias. CONCLUSIONS:Four preoperative predictors, supported by pathologically confirmed low-volume disease, provide a practical framework to refine selection for active surveillance and focal therapy in GS 3 + 4 disease. External prospective validation is warranted.
Many patients who receive prostate magnetic resonance imaging are classified as Patient Imaging Reporting and Data Systems level 3 (PI-RADS 3), which is inconclusive for cancer. An important question is whether PI-RADS 3 patents should receive a biopsy. Prostate biopsy has a 4.6% chance of complications including a 1.3% chance of a hospital or emergency room visit. I critically examine the literature on the standard endpoint for PI-RADS 3 decision-making, namely clinically significant prostate cancer (csPCa) determined on biopsy. Some methods for estimating the probability of csPCa are statistically flawed. Importantly, even if there were no methodological flaws, these estimates have limited information for decision-making because the benefit of detecting csPCa on biopsy is not well established. Therefore, PI-RADS 3 patients should consider events after biopsy. The prostate testing for cancer and treatment trial of patients with localized prostate cancer found similar probabilities of prostate cancer death among patients randomized to active monitoring, prostatectomy, and radiotherapy. Adding perspective, based on calculations from the results of this trial, the probability of prostate cancer death is much smaller than the probability of death from other causes, particularly in older patients. Therefore, for PI-RADS 3 patients who would choose active monitoring if diagnosed with csPCa on biopsy, a reasonable decision is no biopsy with active monitoring.
Objectives To understand the unmet needs of bladder cancer survivors in the acute recovery after cystectomy and how remote monitoring may improve their care. These results are part of user-centered design studies on a remote monitoring recovery aid. Methods We invited bladder cancer survivors who underwent a radical cystectomy and their support persons from bladder cancer survivorship groups. We conducted semi-structured interviews regarding participants’ experiences during recovery from cystectomy, their perspectives regarding unmet needs, and the resources they used during the perioperative period, emphasizing the 2 weeks following hospital discharge. Transcripts were coded using a deductive/inductive approach. Coded excerpts were summarized to develop themes and subthemes. Findings were refined as needed by consensus to accurately capture participants’ experiences. Results A total of 20 bladder cancer survivors and 5 primary support persons were included. Patient participants were on average 3 years from their cystectomy. Barriers to acute recovery were categorized into system- and patient-level challenges, including difficulty connecting with knowledgeable providers and with information, as well as mental/emotional and physical hurdles. Three key facilitators to patients’ acute recovery following cystectomy included identifying indicators of physical progress, facilitating access to provider recommendations, and implementing the survivor perspective into recovery support. Conclusions This study classified barriers and facilitators to cystectomy recovery. The majority of participants expressed interest in remote monitoring programs. Opportunities exist for stakeholders to improve the acute recovery experience for cystectomy patients through mobile interventions delivered via smartphones and wearable devices.
INTRODUCTION:Deferred cytoreductive nephrectomy (dCN) is a selective strategy for managing metastatic renal cell carcinoma (mRCC), in the era of immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI), particularly for patients who achieve favorable responses to initial systemic therapy. This study aims to describe the clinical outcomes of dCN following first-line systemic treatment within a sequential management approach. METHODS:This multi-institutional retrospective study included 50 patients with clear cell mRCC who underwent dCN after first-line therapy. Patients were categorized according to treatment regimen (TKI monotherapy or ICI-based combinations). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Prognostic factors were evaluated with Cox proportional hazards regression. A P-value < 0.05 was considered statistically significant. RESULTS:Median follow-up was 19 months (range 1-174 months). First-line therapy included ICI + ICI in 24%, ICI + TKI in 46%, and TKI alone in 30% of patients. The overall response rate was 64%, and the disease control rate was 84%. Median time from systemic therapy initiation to cytoreductive nephrectomy was 5.6 months. Median PFS was 36 months, 12-, 36-, and 60-month PFS rates of 77%, 49%, and 40%, respectively. Longer PFS occurred in patients with a Karnofsky performance status (KPS) >80% (51 vs. 14 months; P = 0.037) and complete response (P = 0.0021). Median OS reached 91 months. Limitations included a retrospective design and a modest sample size. CONCLUSIONS:dCN may offer durable benefit in well-selected patients achieving disease control and good performance status after systemic therapy. The optimal timing remains uncertain and warrants validation in larger prospective trials.
INTRODUCTION:Estimated glucose disposal rate (eGDR) is a validated surrogate marker of insulin sensitivity derived from clinical metabolic parameters. This study investigated the association between eGDR and prostate cancer (CaP) risk in the U.S. general population. MATERIAL AND METHODS:We analyzed data from male 22,874 participants in the National Health and Nutrition Examination Survey (NHANES) 1999 to 2018. eGDR was calculated using waist circumference, hemoglobin A1c, and hypertension status. CaP status was determined from self-reported physician diagnoses. Multivariable logistic regression, restricted cubic spline analysis, and receiver operating characteristic (ROC) curve analysis were performed to evaluate associations. RESULTS:Among study participants, 686 men had CaP. Patients with CaP demonstrated significantly lower eGDR levels compared to controls (5.99 vs. 7.71 mg/kg/min, P < 0.001). Multivariable logistic regression revealed that each unit increase in eGDR was associated with an 11.6% reduction in CaP risk (OR: 0.884, 95% CI: 0.818-0.956, P = 0.002). Quartile analysis demonstrated a robust dose-response relationship, with the highest quartile showing a 55.7% risk reduction (OR: 0.443, 95% CI: 0.234-0.838, P = 0.012). Restricted cubic spline analysis confirmed a predominantly linear inverse association. ROC analysis showed eGDR achieved superior discriminative performance compared to other metabolic parameters. CONCLUSIONS:Higher eGDR levels are significantly associated with reduced CaP risk. These findings support eGDR as a potential biomarker for CaP risk assessment.
Background Perioperative mortality is usually reported as percentages, although the same risk can also be expressed as natural frequencies (e.g., 1-in-N). Presenting both formats may provide complementary ways of communicating perioperative risk in clinical settings. Objective To compare 30- and 90-day mortality across major urologic cancer surgeries when expressed as percentages and natural frequencies, and to provide descriptive benchmarks for perioperative risk communication. Methods We conducted a literature-based review of national, multinational, and large-scale cohort datasets reporting perioperative mortality after radical nephrectomy (RN), partial nephrectomy (PN), radical nephroureterectomy (RNU), radical cystectomy (RC), and radical prostatectomy (RP), alongside a retrospective real-world cohort from the AGEHA database. Results Across all procedures, mortality risk ranged from 0.02% to 2.70% at 30 days and from 0.07% to 5.57% at 90 days, corresponding to natural frequencies from 1-in-5,577 to 1-in-37 patients. Radical cystectomy showed the highest perioperative mortality (30-day 1.83%, 1-in-55; 90-day 3.83%, 1-in-26), whereas radical prostatectomy showed the lowest (30-day 0.12%, 1-in-820; 90-day 0.21%, 1-in-482). The 90/30-day mortality ratio, presented as a descriptive indicator of delayed postoperative risk, varied across procedures from 1.04 in RN to 2.56 in RNU. Residual heterogeneity and possible overlap between datasets remain limitations. Conclusions Percentages and natural frequencies provide mathematically equivalent but complementary ways of presenting postoperative mortality. Reporting both formats alongside international benchmark estimates may support clearer risk communication and contextual interpretation in urologic oncology.
PURPOSE:To evaluate the risk of suicide among patients with testicular cancer, with particular emphasis on the associations with disease stage and timing from diagnosis. METHODS:The Surveillance, Epidemiology, and End Results database was analyzed to identify patients diagnosed with testicular cancer (2000-2021). Sociodemographic and oncologic factors were compared between those who were alive at last follow-up and those who died of suicide. Standardized mortality ratios (SMR) were calculated to assess the risk of suicide in patients with testicular cancer compared to that of an age-adjusted gender-matched US population, stratified by disease stage and time from diagnosis (<1, 1-5, and 5-10 years). RESULTS:Among 46,395 patients with testicular cancer, 125 (0.27%) died by suicide. Variables associated with increased risk of suicide included relationship status (separated, divorced, or widowed) and race. The SMR for suicide for patients with testicular cancer were significantly elevated compared to an age-adjusted gender-matched US general population (1.31; 95% confidence interval [CI]: 1.29, 1.35). Suicide SMR were significant across all disease stages and increased with advancing disease stage: localized (SMR: 1.07), regional (SMR: 1.48), and distant (SMR: 2.29). Suicide risk was greatest within the first year after diagnosis (SMR: 2.21; 95% CI: 2.10, 2.32) and persisted at 1 to 5 years (SMR: 1.24; 95% CI: 1.19, 1.29) and 5 to 10 years (SMR: 1.08; 95% CI: 1.03, 1.14) after diagnosis. CONCLUSION:Patients with testicular cancer face a significantly elevated risk of suicide, particularly within the first year following diagnosis, and remain at a persistently higher risk of suicide long after their diagnosis. These findings underscore the need for early targeted psychosocial screening and mental health support to optimize survivorship.
PURPOSES:To evaluate first-line metastatic renal cell carcinoma regimens using restricted mean survival time (RMST), which directly conveys absolute survival benefit, integrated with toxicity and cost. MATERIALS AND METHODS:Four pivotal phase 3 randomized trials comparing immune-based combinations were analyzed. Overall survival (OS) and progression-free survival (PFS) were reconstructed from published data, and absolute benefit from the control was expressed as the difference in RMST (dRMST). Drug cost, grade ≥3 adverse events (AEs; symptomatic and any), and high-dose corticosteroid (HDS) use were normalized per RMST month gained. Correlations between hazard ratio (HR) and dRMST were assessed. Principal component analysis (PCA) using incremental RMST, total incremental cost, and symptomatic grade ≥3 AEs was performed to explore multidimensional trade-offs. RESULTS:OS dRMST gains were greatest with nivolumab-cabozantinib (4.15 months), followed by lenvatinib-pembrolizumab (3.53), nivolumab-ipilimumab (2.75), and pembrolizumab-axitinib (2.68). PFS gains were 10.07, 6.49, 4.39, and 1.44 months, respectively. dRMST strongly correlated with (1 - HR) for PFS (R² = 0.988, p = 0.006) and showed a positive trend for OS (R² = 0.890, p = 0.056). OS cost per month gained ranged from $52,207 (nivolumab-ipilimumab) to $293,168 (lenvatinib-pembrolizumab), whereas PFS cost per month gained was relatively consistent ($99,701-$111,721). Symptomatic grade ≥3 AEs per OS month gained were lowest with nivolumab-cabozantinib (<1%) and highest with lenvatinib-pembrolizumab (6%). PCA demonstrated distinct multidimensional positioning among regimens, with differing alignment of 3 factors between OS and PFS. CONCLUSIONS:Integrated RMST-based analyses reveal clinically relevant trade-offs across regimens and distinct multidimensional profiles that may inform comparative treatment interpretation.
PURPOSE:Modulation of autophagy in cancer treatment has attracted considerable interest, as it can contribute to cell death. Several studies have shown that inhibition of casein kinase 1α (CK1α) induces autophagy-mediated cell death in various cancer cell lines. As the role of CK1α in autophagy regulation and cell death in prostate cancer (CaP) cell lines remains unclear, this study aimed to investigate it. MATERIALS AND METHODS:Three human CaP cell lines, LNCaP, PC3, and DU145, were used in this study. Real-time PCR was conducted to determine the basal mRNA expression of CK1α and autophagy markers, including ULK1, WIPI1, LC3B, and p62, in the CaP cell lines. The MTT assay was used to measure the cytotoxic effect of the CK1 inhibitor D4476 (0-500 µM) in LNCaP and PC3 cell lines, both alone and after pretreatment with the autophagy inhibitor wortmannin (1 µM), for 48 hours. To investigate the effect of CK1α inhibition on the expression of autophagy-related genes, D4476 at doses of 62.5 and 31.25 µM for the LNCaP cell line and at doses of 31.25 and 15.62 µM for the PC3 cell line was added to the culture medium, both alone and after pretreatment with wortmannin (1 µM), for 48 hours. The mRNA levels of autophagy markers were then quantified by real-time PCR. RESULTS:Our results showed that, at the basal level compared to the LNCaP cell line, the PC3 and DU145 cell lines upregulated CK1α mRNA expression while downregulating mRNA levels of autophagy markers. We also found that CK1α inhibition reduced the viability of LNCaP and PC3 cell lines in a dose-dependent manner, accompanied by increased expression of autophagy-related genes in the LNCaP cell line and their downregulation in the PC3 cell line. Furthermore, our data showed that pretreatment with wortmannin differentially modulated the effects of D4476, potentiating them in PC3 cells while having no effect in LNCaP cells. CONCLUSIONS:Our findings demonstrate that CK1α differentially regulates autophagy in CaP cell lines in a cell type-dependent manner. These results suggest that CK1α inhibition promotes pro-death autophagy in LNCaP cells while suppressing pro-survival autophagy in PC3 cells, highlighting CK1α as a potential therapeutic target in CaP management.
Background Concordance of NECTIN-4 gene and protein expression and clinic-pathologic associations in matched bladder cancer (BC) triplets, defined as histological specimens from transurethral resection of the bladder (TUR-B), radical cystectomy (RC), and lymphadenectomy (LA) from the same patient, remains unknown. With Enfortumab Vedotin (EV) potentially moving into earlier treatment settings, understanding expression of NECTIN-4 and other targets in archival tissue samples is important. This study characterized protein expression of NECTIN-4 and gene expression of NECTIN4, TACSTD2, ERBB2, PD-L1 and PD1 in matched BC triplet specimens and correlated findings with survival endpoints. Methods This retrospective study analyzed NECTIN-4 protein expression and gene expression of 6 target genes using immunohistochemistry and quantitative real-time polymerase chain reaction in matched TUR-B, RC, and LA tissue samples from 27 patients with BC. NECTIN-4 was validated in 3 independent BC cohorts. Protein and gene expression were correlated with clinic-pathologic characteristics. Prognostic associations with survival were analyzed using Kaplan-Meier estimates, log-rank tests and Cox proportional hazard models. Results Median NECTIN-4 protein expression differed significantly across tissues types with highest levels in TUR-B, lower levels in RC, and intermediate levels in LA specimens Quantitative analysis confirmed significant differences in H-scores across specimens. Expression of NECTIN-4, TACSTD2, PD-L1 and ERBB2 varied significantly across triplets. NECTIN-4 protein expression was not associated with overall or progression-free survival, whereas NECTIN-4 gene expression showed significant but contradictory survival associations in different BC cohorts. Conclusion NECTIN-4 expression differs by tissue type, limiting prognostic value and supporting site-specific biomarker assessment in BC.
Background: Radical cystectomy with urinary diversion is the standard treatment for muscle-invasive bladder cancer. When bowel segments are used for diversion, patients are at risk for metabolic complications, particularly acidosis and electrolyte imbalances. GLP-1 receptor agonists (GLP-1 RAs) have shown renal-protective and metabolic benefits in diabetic patients. This study evaluates whether GLP-1 RA use is associated with reduced metabolic complications following radical cystectomy. Methods: A retrospective cohort study using the TriNetX US Collaborative Network was conducted. Adults (>= 18 years) who underwent radical cystectomy between 2005 and 2024 were included. Patients were stratified by GLP-1 RA exposure and matched for demographics and comorbidities. Outcomes included metabolic acidosis, potassium abnormalities, hypocalcemia, other electrolyte/acid-base disorders, and acute kidney failure occurring within 2-years of radical cystectomy. Results: After matching, 896 patients (448 per cohort) were included. GLP-1 RA use was associated with lower rates of acidosis (relative risk [RR] 1.6, 14.5% vs. 24.1%, p = 0.001), potassium abnormalities (RR 1.6, 16.8% vs. 26.7%, p = 0.005), hypocalcemia (RR 2.5, 2.4% vs. 6.0%, p = 0.009), other electrolyte/acid-base disorders (RR 1.6, 22.9% vs. 36.3%, p = 0.002), and acute kidney failure (RR 1.4, 19.8% vs. 28.0%, p = 0.04). On Cox proportional hazards modeling, GLP-1 RA use was associated with reduced incidence of acidosis (Hazard ratio (HR) 0.65, p = 0.0025), potassium abnormalities (HR 0.63, p = 0.0004), hypocalcemia (HR 0.40, p = 0.013), other electrolyte/acid-base disorders (HR 0.59, p < 0.0001), and acute kidney failure (HR 0.54, p < 0.0001). Kaplan-Meier curves showed improved event-free survival in the GLP-1 RA cohort for each of these outcomes (p for all < 0.05). Conclusion: GLP-1 RA use was associated with fewer metabolic and electrolyte complications post-cystectomy. These findings warrant further investigation into their potential protective role in mitigating these disorders.
