Lower urinary tract symptoms in elderly men: Considerations for prostate cancer testing.

PURPOSE: Both lower urinary tract symptoms (LUTS) and prostate cancer (PCa) are common in elderly men. While LUTS are generally due to a benign etiology, they may provoke an evaluation with prostate-specific antigen (PSA), which can lead to a cascade of further testing and possible overdiagnosis in patients with competing risks. There is limited patient and provider understanding of the relationship between LUTS and PCa risk, and a lack of clarity in how to evaluate these men to balance appropriate diagnosis of aggressive PCa with avoidance of overdiagnosis. METHODS: A literature review was performed using keywords to query the electronic database PubMed. All articles published before November 2023 were screened by title and abstract for articles relevant to our subject. RESULTS: Epidemiological studies suggest that LUTS and PCa are largely independent in elderly men. The best available tools to assess PCa risk include PSA permutations, novel biomarkers, and imaging, but there are limitations in older men based on lack of validation in the elderly and unclear applicability of traditional definitions of "clinically significant" disease. We present a three-tiered approach to evaluating these patients. CONCLUSION: Elderly men commonly have LUTS as well as a high likelihood of indolent PCa. A systematic and shared decision-making-based approach can help to balance objectives of appropriate detection of phenotypically dangerous disease and avoidance of over-testing and overdiagnosis.

Consistent predictive ability of prostate-specific antigen density prediction model for clinically significant prostate cancer across age strata.

BACKGROUND: Prebiopsy prostate-specific antigen density (PSAD) is a well-known predictor of clinically significant prostate cancer (csPCa). Since prostate-specific antigen (PSA) and prostate volume (PV) increase normally with aging, PSAD thresholds may vary. The purpose of the study was to determine if PSAD was predictive of csPCa in different age strata. METHODS: We retrospectively reviewed our institutional database for patients who underwent multiparametric magnetic resonance imaging (MRI) between January 2016 and December 2021. We included patients who had post-MRI prostate biopsies. Based on age, we divided our cohort into four subgroups (groups 1-4): <55, 55-64, 65-74, and ≥75 years old. PSAD accuracy was estimated by the area under the curve (AUC) as a predictive model for differentiating csPCa between the groups. CsPCa was defined as a Gleason Grade Group 2 or higher. Three different PSAD thresholds (0.1, 0.15, and 0.2) were tested across the groups for sensitivity, specificity, and positive predictive value (PPV) and negative predictive value (NPV). Chi-square and analysis of variance tests were used for bivariate analysis. All analys were completed using R 4.3 (R Core Team, 2023). RESULTS: Among 1913 patients, 883 (46.1%) had prostate biopsies. In groups 1, 2, 3, and 4, there were 62 (7%), 321 (36.4%), 404 (45.8%), and 96 (10.9%) patients, respectively. Median PSA was 5.6 (interquartile range 3.4-8.1), 6.2 (4.8-9), 6.8 (5.1-9.7), and 9 (5.6-13), respectively (p < 0.01). Median PV was 42.3 (30-62), 51 (36-77), 55.5 (38-85.9), and 59.3 (42-110) mL, respectively (p < 0.01). No difference was observed in median PSAD between age groups 1-4 (0.1 [0.07-0.16], 0.11 [0.08-0.18], 0.1 [0.07-0.19], and 0.1 [0.07-0.2]), respectively (p = 0.393). CsPCa was diagnosed in 241 (27.3%) patients, of which 10 (16.1%), 65 (20.2%), 121 (30%), and 45 (46.7%) were in groups 1-4, respectively (p < 0.001). For groups 1-4, the PSAD AUC for predicting csPCa was 0.75, 0.68, 0.71, and 0.74. While testing PSAD threshold of 0.15 across the different age groups (1-4), the PPV vs. NPV was 39.1 vs. 93.2, 33.6 vs. 87, 50.9 vs. 80.8, and 66.1 vs. 64.7, respectively. CONCLUSIONS: PSAD prediction model was found to be similar among different age groups. In young patients, PSAD had a high NPV but low PPV. With increasing age, the opposite trend was observed, likely due to higher disease prevalence. While PSAD thresholds may be less useful in older patients to rule out higher-grade prostate cancer, the clinical consequences of these diagnoses require a case-by-case evaluation.

Characterizing the Genomic Landscape of the Micropapillary Subtype of Urothelial Carcinoma of the Bladder Harboring Activating Extracellular Mutations of ERBB2.

The micropapillary subtype of urothelial carcinoma (MPUC) of the bladder is a very aggressive histological variant of urothelial bladder cancer (UBC). A high frequency of MPUC contains activating mutations in the extracellular domain (ECD) of ERBB2. We sought to further characterize ERBB2 ECD-mutated MPUC to identify additional genomic alterations that have been associated with tumor progression and therapeutic response. In total, 5,485 cases of archived formalin-fixed, paraffin-embedded UBC underwent comprehensive genomic profiling to identify ERBB2 ECD-mutated MPUC and evaluate the frequencies of genomic co-alterations. We identified 219 cases of UBC with ERBB2 ECD mutations (74% S310F and 26% S310Y), of which 63 (28.8%) were MPUC. Genomic analysis revealed that TERT, TP53, and ARID1A were the most common co-altered genes in ERBB2-mutant MPUC (82.5%, 58.7%, and 39.7%, respectively) and did not differ from ERBB2-mutant non-MPUC (86.5%, 51.9%, and 35.3%). The main differences between ERBB2 ECD-mutated MPUC compared with non-MPUC were KMT2D, RB1, and MTAP alterations. KMT2D and RB1 are tumor-suppressor genes. KMT2D frequency was significantly decreased in ERBB2 ECD-mutated MPUC (6.3%) in contrast to non-MPUC (27.6%; P < .001). RB1 mutations were more frequent in ERBB2 ECD-mutated MPUC (33.3%) than in non-MPUC (17.3%; P = .012). Finally, MTAP loss, an emerging biomarker for new synthetic lethality-based anticancer drugs, was less frequent in ERBB2 ECD-mutated MPUC (11.1%) than in non-MPUC (26.9%; P = .018). Characterizing the genomic landscape of MPUC may not only improve our fundamental knowledge about this aggressive morphological variant of UBC but also has the potential to identify possible prognostic and predictive biomarkers that may drive tumor progression and dictate treatment response to therapeutic approaches.

Outcomes of upper tract urothelial carcinoma with isolated lymph node involvement following surgical resection: implications for multi-modal management.

BACKGROUND: There are limited data on the oncologic outcomes of upper tract urothelial carcinoma with isolated lymph node (LN) involvement (pN+ M0) following surgical resection. We examined pN+ M0 UTUC in a large, nationwide oncology dataset to characterize its natural history, describe trends in utilization of perioperative chemotherapy, and identify clinicopathologic features associated with survival. METHODS: We identified 794 patients aged 18-89 years who underwent radical nephroureterectomy with lymph node dissection for pN+ M0 UTUC from 2006 to 2013 in the National Cancer Database. The associations of clinicopathologic features with overall survival (OS) were evaluated using Cox regression models, and a simplified risk score was created. RESULTS: Median follow-up among survivors was 39.5 months, during which time 555 (70%) patients died. Over the study period, neoadjuvant chemotherapy utilization increased from 6.7 to 14.2% (p = 0.002), while adjuvant chemotherapy utilization remained stable (42.7 to 44.3%; p = 0.86). One-, 5-, and 8-year OS rates were 63.7%, 24.2%, and 18.7%, respectively. On multivariable analysis, older age, larger tumor size, higher pT stage, positive surgical margins, number of positive LNs, and non-receipt of adjuvant chemotherapy were independently associated with worse OS. A simplified risk score consisting of age, tumor size, pT stage, number of positive LNs, and margin status was created with predicted 5-year OS ranging from 12 to 44%. CONCLUSIONS: In this large, contemporary cohort, pN+ M0 UTUC was associated with a 5-year OS of only 24%. Clinicopathologic predictors of survival after surgical resection may improve risk-stratification, counseling, and selection of patients for multimodal management.

Targeted imaging of urothelium carcinoma in human bladders by an ICG pHLIP peptide ex vivo.

Bladder cancer is the fifth most common in incidence and one of the most expensive cancers to treat. Early detection greatly improves the chances of survival and bladder preservation. The pH low insertion peptide (pHLIP) conjugated with a near-infrared fluorescent dye [indocyanine green (ICG)] targets low extracellular pH, allowing visualization of malignant lesions in human bladder carcinoma ex vivo. Cystectomy specimens obtained after radical surgery were immediately irrigated with nonbuffered saline and instilled with a solution of the ICG pHLIP construct, incubated, and rinsed. Bladders were subsequently opened and imaged, the fluorescent spots were marked, and a standard pathological analysis was carried out to establish the correlation between ICG pHLIP imaging and white light pathological assessment. Accurate targeting of bladder lesions was achieved with a sensitivity of 97%. Specificity is 100%, but reduced to 80% if targeting of necrotic tissue from previous transurethral resections or chemotherapy are considered as false positives. The ICG pHLIP imaging agent marked high-grade urothelial carcinomas, both muscle invasive and nonmuscle invasive. Carcinoma in situ was accurately diagnosed in 11 cases, whereas only four cases were seen using white light, so imaging with the ICG pHLIP peptide offers improved early diagnosis of bladder cancers and may also enable new treatment alternatives.

The role of lymph node dissection in the management of renal cell carcinoma: a systematic review and meta-analysis.

Our objective was to evaluate the role of retroperitoneal lymph node dissection (LND) in non-metastatic (M0) and metastatic (M1) renal cell carcinoma (RCC). We searched Medline, EMBASE, Web of Science and Scopus from database inception to 29 August 2017 for studies of patients who underwent partial or radical nephrectomy for M0 or M1 RCC. Two investigators independently selected studies for inclusion. Risk of bias was assessed using the Newcastle-Ottawa scale, Cochrane Collaboration tool and National Heart, Lung and Blood Institute Quality Assessment Tool. Random effects meta-analysis was performed for all-cause-mortality. The GRADE approach was used to characterize quality of evidence. A total of 51 unique studies were included in the qualitative systematic review. Risk of bias was low in 41/51 (80%) studies. LND was not associated with all-cause mortality in either M0 (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.92-1.12; I2 = 0%; four studies), M1 (HR 1.04, 95% CI 0.83-1.29; I2 = 0%; two studies), or pooled M0 and M1 settings (HR 1.00, 95% CI 0.92-1.09; I2 = 0%; seven studies), with no statistically significant differences according to M stage subgroups (P = 0.50). In the three studies that examined M0 subgroups with a high risk of nodal metastasis, LND was not associated with improved oncological outcomes. Studies on the association of extent of LND with survival reported inconsistent results. Meanwhile, a small proportion of patients with pN1M0 disease demonstrate durable long-term oncological control after surgery, with 10-year cancer-specific survival of 21-31%. Nodal involvement is independently associated with adverse prognosis in both M0 and M1 settings. GRADE quality of evidence was moderate or low for the outcomes examined. Although LND yields independent prognostic information, the existing literature does not support a therapeutic benefit to LND in either M0 or M1 RCC. High-risk M0 patient groups warrant further study, as a subset of patients with isolated nodal metastases experience long-term survival after surgical resection.

Effectiveness and safety of computed tomography-guided radiofrequency ablation of renal cancer: a 14-year single institution experience in 203 patients.

OBJECTIVES: To define effectiveness and safety of CT-guided radiofrequency ablation (RFA) of renal tumours and prognostic indicators for treatment success. METHODS: Patients with a single treatment of a solitary, biopsy-proven renal tumour with intent to cure over a 14-year period were included (n = 203). Probability of residual disease over time, complication rates and all-cause mortality were assessed in relation to multiple variables. RESULTS: Mean tumour size was 2.5 cm (range 1.0-6.0). Mean follow-up was 34.1 months (range 1-131). There was an increase in likelihood of residual disease for tumours ≥3.5 cm (P < 0.05), clear cell subtype of renal cell carcinoma (P ≤ 0.005) and maximum treatment temperature ≤70 °C (P < 0.05). There was a decrease in likelihood of residual disease for exophytic tumours (P = 0.01) and no difference based on age, gender, tumour location or type of radio freqency (RF) electrode used. Major complications occurred in 3.9 %. Median post-treatment survival was 7 years for patients with tumours <4 cm, and 5-year overall survival was 80 %. Probability of minor complication increased with tumour size (P = 0.03), as did all-cause mortality (P = 0.005). CONCLUSIONS: CT-guided RFA is safe and effective for early-stage renal cancer, particularly for exophytic tumours measuring <3.5 cm. Overall 5-year survival with tumours <4 cm is comparable to partial nephrectomy. KEY POINTS: • Prognostic indicators for success of CT-guided RFA of renal tumours are reported. • Tumour size ≥3.5 cm confers an increased risk for residual tumour. • Clear cell renal cell carcinoma subtype confers increased risk for residual tumour. • Tmax <70 °C within the ablation zone confers increased risk for residual tumour. • Exophytic tumours have a lower probability of residual disease.

Investigating the association between blue light cystoscopy utilization and social determinants of health.

INTRODUCTION: Blue light cystoscopy (BLC) improves bladder cancer (BCa) detection. No studies have evaluated socioeconomic inequity in the utilization of BLC. METHODS: An institutional bladder tumor (TURBT) database (2016-2023) was retrospectively reviewed and BLC and white light cystoscopy (WLC) recipients were compared. Demographic and insurance data were collected. Socioeconomic Status (SES) was determined using a validated national and Rhode Island Area Deprivation Index (ADI). RESULTS: 2122 Rhode Island patients underwent TURBT and 32.23% had BLC. BLC recipients were younger (mean age 71.5 vs 73.8 years, p < 0.001), more likely married (69.6% vs 57.2%, p < 0.001), more likely English speakers (93.3% vs 91.9%, p = 0.015), and more likely to have private insurance (34.2% vs 27%, p = 0.001). BLC recipients had less socioeconomic disadvantage (p < 0.001): lower mean National (36.2 vs 38.7) and State (4.8 vs 5.2) ADI. CONCLUSION: SES is associated with BLC utilization, which may negatively influence BCa outcomes.

The Interplay Between Adult-Onset Hypogonadism and Prostate Cancer: A Literature Review.

The interplay between endogenous testosterone (Te) and prostate cancer (PCa) has long been recognized, with androgen deprivation therapy (ADT) being a cornerstone of advanced and metastatic PCa management. However, the association between Te levels and PCa risk remains complex and not fully understood. This review delves into the complex relationship between adult-onset hypogonadism (AOH) and PCa, shedding light on the complexities surrounding PCa risk and disease aggressiveness. Despite the significant prevalence of PCa among men, particularly as they age, and the emergence of AOH as a prevalent health concern, data regarding their association remains heterogeneous and inconsistently documented. While some studies suggest a potential correlation between low Te levels and decreased PCa detection rates, others indicate a higher risk of aggressive pathological features, primarily observed in prostatectomy cohorts. It's noteworthy that there's evidence indicating hypogonadal men might face an increased risk of reclassification during active surveillance (AS) of low-risk disease. This is supported by the observation of elevated rates of disease upgrading in historical cohorts of low-risk prostatectomies. These contradictory findings are poorly reflected in treatment guidelines. Further research is imperative to comprehensively understand the clinical and associative correlations between AOH and PCa risk and biology, thereby informing more effective management strategies in the future.

Investigation of Disparity of Urologic Fellowship Match Rates by Gender and US Versus International Medical Graduates Over the Past Decade.

OBJECTIVE: To investigate the influence of postgraduate medical education (US vs international) and gender on applicant matching for postgraduate training across different urologic sub-specialties. METHODS: Match statistics of 5 societies that participated in the AUA fellowship match between 2010 and 2024 were retrospectively reviewed. Societies included: Endourology Society (EUS), Society for Urological Oncology (SUO), American Society of Andrology (ASA), Society of Genitourinary Reconstructive Surgeons (GURS), and Society of Pediatric Urology (SPU). Candidates were classified based on gender (male/female) and their postgraduate medical education: local graduates from the United States or Canada (US/Ca) and international medical graduates (IMGs). The match odds were analyzed using the Chi-square test, while trends were assessed through the Mann-Kendall test. RESULTS: Overall, 2439 applicants applied for 1627 programs from 2010 to 2024, comprising 1998 males (81.8%), 399 females (16.4%), and 42 undisclosed (1.7%). There were 1486 US/Ca graduates (60.8%) and 953 IMGs (39.2%). Around 1471 (60.6%) applicants were matched with a program, compared to 958 (39.4%) unmatched. The likelihood of US/Ca graduates matching (83.8%) was significantly higher than IMGs (23.3%), OR= 17.5, 95% CI: (14.3, 21.5), P <.001. IMGs had the highest match rate with GURS (33.8%, 47/118) and the lowest with SPU (7%, 1/14). Female applicants had a significantly higher chance of matching 324/399 (81.2%) than male applicants 1139/1998 (57%), OR= 3.26, 95% CI: (2.5, 4.3), P <.001. US/Ca-to-IMGs ratios and the male-to-female ratios were stable throughout the match years. CONCLUSION: Compared to IMGs, U.S./Ca graduates had remarkably higher matching rates. Matching outcomes were also significantly better for female applicants. Further assessment of international involvement and diversity in urological subspecialty roles is warranted.

Assessment of mechanical bowel preparation prior to nephrectomy in the minimally invasive surgery era: insights from a national database analysis in the United States.

Purpose: This study was performed to evaluate the association between mechanical bowel preparation (MBP) and perioperative outcomes following nephrectomy in the minimally invasive surgery (MIS) era. Methods: All partial and radical nephrectomies between 2019 and 2021 from the National Surgical Quality Improvement Program database were evaluated. Thirty-day perioperative outcomes were compared between groups where MBP was performed vs. not, in both the MIS and open surgery (OS) cohorts. A propensity score matching technique was utilized within MIS cases to control for covariates. The chi-square and t tests were used to determine significance. Results: A total of 11,869 cases met the inclusion criteria and were included in the analysis. Of these, 8,204 (69.1%; comprising 65.3% robotic and 34.7% laparoscopic) underwent MIS, while 3,655 (30.9%) underwent OS. The rate of MBP was higher in the MIS group (16.0% vs. 10.0%, p < 0.001). Within the MIS group, MBP was associated with reduced rates of postoperative ileus (0.9% vs. 1.9%, p = 0.02), while other complications were comparable. Propensity score matching showed no association between MBP and postoperative ileus. However, a lower rate of 30-day readmission in the MBP group became statistically significant (4.4% vs. 6.4%, p = 0.01). Conversely, patients in the MBP group also demonstrated higher rates of pneumonia (1.29% vs. 0.46%, p = 0.002) and pulmonary embolism (0.6% vs. 0%, p < 0.001) after matching. Conclusion: MBP practice prior to nephrectomy is infrequent in both OS and MIS cases, with minor differences in perioperative outcomes for patients undergoing MIS. Routine MBP should continue to be excluded from the standard of care for nephrectomy in the MIS era.

Optimising postoperative care: Same-day discharge after transurethral resection of the prostate.

INTRODUCTION: This study aims to assess the feasibility and safety of same-day discharge after transurethral resection of the prostate. MATERIALS AND METHODS: Five years of records were retrospectively analysed. Length of stay categorised patients into Groups 1 (same-day discharge) and 2 (standard-length discharge). Logistic regression analysis was performed, controlling for clinicodemographic factors. Student's t-test compared continuous bladder irrigation and catheter dwell times. RESULTS: A total of 459 patients were identified between 2016 and 2021, 280 in Group 1 and 179 in Group 2, with median ages of 71.0 (interquartile range 36-92) and 72.0 (interquartile range 47-101) years (p = 0.067), respectively. Same-day discharge rates notably increased post-2018 (p = 0.025). Median prostate tissue resected in Group 2 was 7.1g (3.4-12.4g) and in Group 1 was 4.9g (2.4-10.2g; p = 0.034). While continuous bladder irrigation >1 hour was significantly lower in Group 1 than Group 2 (96.8% versus 27.4%; p = 0.0001), catheter dwell times were comparable (70.1 and 70.8 hours, respectively). Control-adjusted results showed a 40% reduction in emergency department representation odds for Group 1 compared with Group 2 (odds ratio = 0.60; 95% confidence interval = 0.37-0.99; p = 0.04). Length of stay was not significantly associated with hospital readmissions (p = 0.11). Continuous bladder irrigation for <1 hour in Group 1 was associated with a reduced emergency department representation (odds ratio = 0.43; 95% confidence interval = 0.197-0.980) but not readmission (odds ratio = 0.413; 95% confidence interval = 0.166-1.104). CONCLUSIONS: Same-day discharge post-transurethral resection of the prostate may be a viable and safe option for carefully selected patients.

Analysis of a large single-center experience with robot-assisted pyeloplasty.

OBJECTIVES: To report a single-center experience with robot-assisted pyeloplasty. METHODS: Medical records of 100 consecutive robot-assisted pyeloplasty cases carried out between May 2004 and August 2010 were retrospectively reviewed, and major perioperative parameters were recorded. Patients underwent functional (renal scan) and/or anatomical (ultrasound or computerized tomoghraphy) imaging at 6 months. RESULTS: The mean patient age was 39.8 years. A total of 12 patients underwent prior attempts at repair. Ureteral stents were placed in all patients except one, and closed-suction drains were placed in 59 patients. There were two intraoperative complications and two postoperative complications requiring surgical intervention. One patient with a complex prior surgical history developed a urine leak that was managed with prolonged drainage. A total of 42 patients were discharged on postoperative day 1, and 44 were discharged on postoperative day 2. Mean length of follow up was 22.8 months. The operative success rate was 96%. CONCLUSIONS: The majority of patients undergoing robot-assisted pyeloplasty can expect a short hospitalization with minimal morbidity. The operative success rate is high, even in patients with prior attempts at repair. Complication rates including urine leaks are quite low, and routine placement of a closed-suction drain is likely to be unnecessary.

Evolution of the HIF targeted therapy in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, affecting hundreds of thousands of people worldwide and can affect people of any age. The pathogenesis of ccRCC is most commonly due to biallelic loss of the tumor suppressor gene VHL. VHL is the recognition subunit of an E3-ubiquitin-ligase-complex essential for degradation of the hypoxia-inducible factors (HIF) 1α and 2α. Dysfunctional degradation of HIF results in overaccumulation, which is particularly concerning with the HIF2α subunit. This leads to nuclear translocation, dimerization, and transactivation of numerous HIF-regulated genes responsible for cell survival and proliferation in ccRCC. FDA-approved therapies for RCC have primarily focused on targeting downstream effectors of HIF, then incorporated immunotherapeutics, and now, novel approaches are moving back to HIF with a focus on interfering with upstream targets. This review summarizes the role of HIF in the pathogenesis of ccRCC, novel HIF2α-focused therapeutic approaches, and opportunities for ccRCC treatment.

Clinical features of patients with MTAP-deleted bladder cancer.

Advanced urothelial carcinoma continues to have a dismal prognosis despite several new therapies in the last 5 years. FGFR2 and FGFR3 mutations and fusions, PD-L1 expression, tumor mutational burden, and microsatellite instability are established predictive biomarkers in advanced urothelial carcinoma. Novel biomarkers can optimize the sequencing of available treatments and improve outcomes. We describe herein the clinical and pathologic features of patients with an emerging subtype of bladder cancer characterized by deletion of the gene MTAP encoding the enzyme S-Methyl-5'-thioadenosine phosphatase, a potential biomarker of response to pemetrexed. We performed a retrospective analysis of 61 patients with advanced urothelial carcinoma for whom demographics, pathologic specimens, next generation sequencing, and clinical outcomes were available. We compared the frequency of histology variants, upper tract location, pathogenic gene variants, tumor response, progression free survival (PFS) and overall survival (OS) between patients with tumors harboring MTAP deletion (MTAP-del) and wild type tumors (MTAP-WT). A propensity score matching of 5 covariates (age, gender, presence of variant histology, prior surgery, and prior non-muscle invasive bladder cancer) was calculated to compensate for disparity when comparing survival in these subgroups. Non-supervised clustering analysis of differentially expressed genes between MTAP-del and MTAP-WT urothelial carcinomas was performed. MTAP-del occurred in 19 patients (31%). Tumors with MTAP-del were characterized by higher prevalence of squamous differentiation (47.4 vs 11.9%), bone metastases (52.6 vs 23.5%) and lower frequency of upper urinary tract location (5.2% vs 26.1%). Pathway gene set enrichment analysis showed that among the genes upregulated in the MTAP-del cohort, at least 5 were linked to keratinization (FOXN1, KRT33A/B, KRT84, RPTN) possibly contributing to the higher prevalence of squamous differentiation. Alterations in the PIK3 and MAPK pathways were more frequent when MTAP was deleted. There was a trend to inferior response to chemotherapy among MTAP-del tumors, but no difference in the response to immune checkpoint inhibitors or enfortumab. Median progression free survival after first line therapy (PFS1) was 5.5 months for patients with MTAP-WT and 4.5 months for patients with MTAP-del (HR = 1.30; 95% CI, 0.64-2.63; P = 0.471). There was no difference in the time from metastatic diagnosis to death (P = 0.6346). Median OS from diagnosis of localized or de novo metastatic disease was 16 months (range 1.5-60, IQR 8-26) for patients with MTAP-del and 24.5 months (range 3-156, IQR 16-48) for patients with MTAP-WT (P = 0.0218), suggesting that time to progression to metastatic disease is shorter in MTAP-del patients. Covariates did not impact significantly overall survival on propensity score matching. In conclusion, MTAP -del occurs in approximately 30% of patients with advanced urothelial carcinoma and defines a subgroup of patients with aggressive features, such as squamous differentiation, frequent bone metastases, poor response to chemotherapy, and shorter time to progression to metastatic disease.

Prostate cancer in the elderly: frequency of advanced disease at presentation and disease-specific mortality.

BACKGROUND: The objectives of this study were to determine the frequency of metastatic (M1) prostate cancer (PC) at presentation in different age groups, to examine the association of age with PC-specific mortality, and to calculate the relative contribution of different age groups to the pool of M1 cases and PC deaths. METHODS: Records from 464,918 patients who were diagnosed with PC from 1998 to 2007 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were categorized according to age into groups ages <50 years, 50 to 54 years, 55 to 59 years, 60 to 64 years, 65 to 69 years, 70 to 74 years, 75 to 79 years, 80 to 84 years, 85 to 89 years, and ≥ 90 years. The cumulative incidence of death from PC was computed using the Gray method. RESULTS: The frequency of M1 PC at presentation was 3% for the group aged <75 years, 5% for the group ages 75 to 79 years, 8% for the group ages 80 to 84 years, 13% for the group ages 85 to 89 years, and 17% for the group aged ≥ 90 years. The 5-year cumulative incidence of death from PC was 3% to 4% for all patients with PC in any category aged <75 years, 7% for patients ages 75 to 79 years, 13% for patients ages 80 to 84 years, 20% for patients ages 85 to 89 years, and 30% for patients aged ≥ 90 years. Although patients aged ≥ 75 years at PC diagnosis represented just over a quarter (26%) of all PC cases, they contributed almost half (48%) of all M1 cases and more than half (53%) of all PC deaths. CONCLUSIONS: Compared with younger patients (aged <75 years), older patients were more likely to present with very advanced disease, had a greater risk of death from PC despite higher death rates from competing causes, and contributed more than half of all PC deaths. Awareness of this issue may improve future outcomes for elderly patients with PC.

Neoadjuvant gemcitabine and cisplatin chemotherapy for locally advanced urothelial cancer of the bladder.

BACKGROUND: The purpose of this study was to investigate the effect of neoadjuvant chemotherapy with gemcitabine and cisplatin (GC) on pathologic down-staging of patients with locally advanced urothelial cancer (UC) of the bladder. METHODS: This was a retrospective cohort study of patients treated with radical cystectomy (RC) for clinical stage cT2-T4, N any, M0 bladder UC at Strong Memorial Hospital from 1999 to 2009. The primary exposure variable was use of neoadjuvant chemotherapy (GC vs none). The primary outcome was stage pT0 at RC. Secondary outcomes included other down-staging end points in the bladder (

Identifying additional lymph nodes in radical cystectomy lymphadenectomy specimens.

Lymph node count has prognostic implications in bladder cancer patients who are treated with radical cystectomy. Lymph nodes that are too small to identify grossly can easily be missed, potentially leading to missed nodal metastases and inaccurate nodal counts, resulting in inaccurate prognoses. We investigated whether there is a benefit to submitting the entire lymph node packet for histological examination to identify additional lymph nodes. We prospectively assessed 61 pelvic lymphadenectomy specimens in 14 consecutive patients undergoing radical cystectomy. The specimens were placed in Carnoy's solution overnight, then analyzed for lymph nodes. The residual tissue was entirely submitted to assess for additional lymph nodes. In 61 specimens, we identified 391 lymph nodes, ranging from 4-44 nodes per patient. We identified 238 (61%) lymph nodes with standard techniques and 153 (39%) lymph nodes in submitted residual tissue. The number of additional lymph nodes found in the residual tissue ranged from 0 to 26 (0-75%) per patient. These lymph nodes ranged in size from 0.05 to 1 cm. All additional lymph nodes were negative for metastatic disease. Submitting the entire specimen for histological examination allowed for identification of more lymph nodes in radical cystectomy pelvic lymphadenectomy specimens. However, as none of the additional lymph nodes contained metastatic disease, it is unclear if there is a clinical benefit in evaluating lymph nodes that are neither visible nor palpable in lymphadenectomy specimens.

Prostate-specific antigen testing in older men in the USA: data from the behavioral risk factor surveillance system.

OBJECTIVE: To examine the frequency of PSA testing in men aged ≥75 years before and after the 2008 US Preventive Services Task Force (USPSTF) recommendation to stop prostate-specific antigen (PSA) screening at age 75. MATERIALS AND METHODS: Data were obtained from the Behavioral Risk Factor Surveillance System (BRFSS) surveys completed in 2006, 2008 and 2010. Men aged ≥ 76 years at the time of survey and without a prostate cancer diagnosis were included in the study. The percentage of men who had a PSA test in the year before the survey was computed separately for survey years 2006, 2008 and 2010. RESULTS: The estimated percentages of men with a PSA test in the year before the survey were 60% (95% CI: 58-62%), based on 9033 respondents interviewed in 2006, 63% (95% CI: 62-65%), based on 12,063 respondents interviewed in 2008, and 60% (95% CI: 59-61%), based on 14,782 respondents interviewed in 2010. CONCLUSION: No substantial reduction in the frequency of PSA testing was observed in the BRFSS 2010 survey data compared with the earlier years, suggesting that the USPSTF 2008 recommendation had no major impact on the frequency of PSA testing in older men in the USA.