Adjuvant immune checkpoint inhibitors for urothelial carcinoma: systematic review and Meta-analysis.

PURPOSE: To compare disease-free survival (DFS), overall survival (OS), and adverse events (AEs) among muscle-invasive urothelial carcinoma (MIUC) patients receiving adjuvant immune checkpoint inhibitors (ICIs) versus placebo/observation following radical surgery. METHODS: This was a systematic review/meta-analysis of all published phase 3 randomized controlled trials. MEDLINE, EMBASE, and Cochrane were searched from inception until April 4, 2024. Pooled hazard ratios (HR) and relative risks (RR), plus confidence intervals (CI), were generated using frequentist random-effects modeling. RESULTS: Three trials were identified: IMvigor010, CheckMate 274, and AMBASSADOR. In the overall cohort, adjuvant ICIs significantly improved DFS by 23% (HR = 0.77, 95% CI = 0.65-0.90). No DFS benefit was observed in patients with upper tract disease (HR = 1.19, 95% CI = 0.86-1.64). The highest magnitude of DFS benefit was observed among patients who had received prior neoadjuvant chemotherapy (HR = 0.69) and pathologic node-positive disease (HR = 0.75). A similar DFS benefit was observed irrespective of tumor PD-L1 status. Pooled OS demonstrated a 13% non-significant benefit (HR = 0.87, 95% CI = 0.75-1.01). Grade ≥ 3 immune-mediated AEs occurred in 8.6% and 2.1% of ICI and placebo/observation patients, respectively (RR = 4.35, 95% CI = 1.02-18.5). AEs leading to treatment discontinuation occurred in 14.3% and 0.9% of patients, respectively. CONCLUSION: Adjuvant ICIs confer a DFS benefit following radical surgery for MIUC, particularly among node-positive patients and those who received prior neoadjuvant chemotherapy. The lack of benefit for upper tract disease suggests that alternate adjuvant approaches, including chemotherapy, should be considered for these patients. Tumor PD-L1 status is not a predictive biomarker, highlighting the need for biomarkers in this setting.

BioPrev-C - development and validation of a contemporary prostate cancer risk calculator.

Objectives: To develop a novel biopsy prostate cancer (PCa) prevention calculator (BioPrev-C) using data from a prospective cohort all undergoing mpMRI targeted and transperineal template saturation biopsy. Materials and methods: Data of all men who underwent prostate biopsy in our academic tertiary care center between 11/2016 and 10/2019 was prospectively collected. We developed a clinical prediction model for the detection of high-grade PCa (Gleason score ≥7) based on a multivariable logistic regression model incorporating age, PSA, prostate volume, digital rectal examination, family history, previous negative biopsy, 5-alpha-reductase inhibitor use and MRI PI-RADS score. BioPrev-C performance was externally validated in another prospective Swiss cohort and compared with two other PCa risk-calculators (SWOP-RC and PBCG-RC). Results: Of 391 men in the development cohort, 157 (40.2%) were diagnosed with high-grade PCa. Validation of the BioPrev C revealed good discrimination with an area under the curve for high-grade PCa of 0.88 (95% Confidence Interval 0.82-0.93), which was higher compared to the other two risk calculators (0.71 for PBCG and 0.84 for SWOP). The BioPrev-C revealed good calibration in the low-risk range (0 - 0.25) and moderate overestimation in the intermediate risk range (0.25 - 0.75). The PBCG-RC showed good calibration and the SWOP-RC constant underestimation of high-grade PCa over the whole prediction range. Decision curve analyses revealed a clinical net benefit for the BioPrev-C at a clinical meaningful threshold probability range (≥4%), whereas PBCG and SWOP calculators only showed clinical net benefit above a 30% threshold probability. Conclusion: BiopPrev-C is a novel contemporary risk calculator for the prediction of high-grade PCa. External validation of the BioPrev-C revealed relevant clinical benefit, which was superior compared to other well-known risk calculators. The BioPrev-C has the potential to significantly and safely reduce the number of men who should undergo a prostate biopsy.

Prognostic value of pretreatment inflammatory markers in localised prostate cancer before radical prostatectomy.

PURPOSE: There is growing evidence of an association between inflammatory processes and cancer development and progression. In different solid tumor entities, a pronounced inflammatory response is associated with worse oncological outcome. In this study, we aim to evaluate the prognostic role of clinically established pretreatment inflammatory markers in patients with localised prostate cancer (PCa) before radical prostatectomy (RP). METHODS: A total of 641 men met our inclusion criteria and were followed prospectively for a median of 2.85 years. Univariable logistic and Cox regression analysis were performed to analyse associations between preoperative inflammatory markers and tumor characteristics, and biochemical recurrence free survival (BRFS). RESULTS: Median age at RP was 64 years. Gleason Score (GS) 7a (263, 41%) was the most prevalent histology, whereas high-risk PCa (≥ GS 8) was present in 156 (24%) patients. Lympho-nodal metastasis and positive surgical margin (PSM) were detected in 69 (11%) and 180 (28%) patients, respectively. No statistically relevant association could be shown between pretreatment inflammatory markers with worse pathological features like higher tumor stage or grade, nodal positive disease or PSM (for all p > 0.05). Additionally, pretreatment inflammatory markers were not associated with a shorter BRFS (p > 0.05). Known risk factors (tumor grade, tumor stage, nodal positivity and positive surgical margins) were all associated with a shorter BRFS (for all p < 0.0001). CONCLUSION: In this large prospective cohort, preoperative inflammatory markers were not associated with worse outcome.

Do Swiss urologists and Swiss internists screen themselves and their relatives for prostate cancer? A questionnaire study.

PURPOSE: Prostate-specific antigen (PSA) screening for men at risk of prostate cancer is controversial. The current recommendation is to raise awareness of prostate cancer and offer PSA screening in accordance with shared decision- making. Whether the possibility of a PSA screen is discussed with the patient depends on the treating physician, but data on physicians' attitudes towards PSA screening are scarce. This study aimed to examine internists' and urologists' personal PSA screening activity as an indicator of their attitude towards PSA screening. MATERIALS AND METHODS: Members of the Swiss Society of Urology and the Swiss Society of General Internal Medicine were asked in 08/2020 to anonymously complete an online survey about personal PSA screening behaviour for themselves, their fathers, brothers and partners. Categorical and continuous variables were compared by chi-squared tests and t-tests, respectively. RESULTS: In total, 190/295 (response rate: 64%) urologists and 893/7400 (response rate: 12%) internists participated in the survey. Of the participants, 297/1083 (27.4%) were female. Male urologists >50 years of age screened themselves more often than male internists >50 years of age (89% vs 70%, p <0.05). Furthermore, urologists reported recommending screening statistically significantly more often than internists to their brother, father or partner regardless of their sex (men: 38.1% vs 18.5%; p <0.05; women: 81.8% vs 32.2%; p <0.05).   CONCLUSIONS: Most participating male physicians >50 years of age have screened themselves for prostate cancer. Furthermore, PSA screening of relatives was significantly associated with the urology specialty. The reasons physicians screen themselves substantially more often than the public and why male and female urologists as well as male internists perform PSA screening more frequently in their private environment than female internists should be further examined.

Limited Value of Bladder Wash Cytology During Follow-Up of Patients With Non-muscle Invasive Bladder Cancer.

Aims We aimed to assess the performance of bladder wash cytology (BWC) in daily clinical practice in a pure follow-up cohort of patients previously diagnosed with non-muscle invasive bladder cancer (NMIBC). Materials and methods We analyzed 2064 BWCs derived from 314 patients followed for NMIBC (2003-2016). Follow-up investigations were performed using cystoscopy (CS) in combination with BWC. Patients with suspicious CS and/or positive BWC underwent bladder biopsy or transurethral resection. BWC was considered positive if malignant or suspicious cells were reported. Sensitivity (Sn) and specificity (Sp) were calculated for the entire cohort and separately for low-grade (LG) and high-grade (HG) tumors, and carcinoma in situ (CIS) subgroups. Results A total of 95 recurrences were detected, of which only three were detected by BWC alone. Overall, Sn and Sp of BWC were 17.9% and 99.5%, respectively. For LG disease, these numbers were 14.0% and 100%, and for HG disease, these were 22.2% and 99.1%, respectively. For patients with CIS at initial diagnosis, Sn and Sp were 11.0% and 71.4%, respectively. For isolated primary CIS, Sn was 50.0%, and Sp was 98.2%. Conclusion Routine use of BWC in the follow-up for NMIBC is of limited value even in HG tumors. In the presence of isolated primary CIS, adjunct BWC might be justified.

Validating the total cancer location density metric for stratifying patients with low-risk localized prostate cancer at higher risk of grade group reclassification while on active surveillance.

PURPOSE: To validate a previously proposed prognostic metric, Total Cancer Location (TCLo) density, in a contemporary cohort of men with grade group (GG) 1 prostate cancer (PCa) on active surveillance (AS). METHODS: We evaluated 123 patients who entered AS with maximum GG1 PCa at diagnostic and/or confirmatory biopsy. TCLo was defined as the total number of PCa locations identified on both biopsy sessions. TCLo density was calculated as TCLo / prostate volume [ml]. Primary endpoint was progression-free survival (PFS), defined as time from confirmatory biopsy to grade group reclassification (GGR) on repeat biopsy or prostatectomy. Optimal cut-point for TCLo density was predefined in a previously reported cohort and applied to this contemporary cohort. Kaplan-Meier and multivariable Cox regression analysis were used to estimate the association of predictors with PFS. RESULTS: During median follow-up of 7.8 years, (IQR 7.3-8.2) 34 men had GGR. Using previously defined cut-points, PFS at 5-years was 60% (95% CI: 44%-81%) vs. 89% (95% CI: 83%-96%) in men with high (≥0.06 ml-1) vs. low (<0.06 ml-1) TCLo density, and 63% (95% CI: 48%-82%) vs. 90% (95% CI: 83%-96%) in men with high (≥3) vs. low (≤2) TCLo (log-rank test: P < 0.0001, respectively). Adjusting for age, prostate volume, percent of positive cores and PSA, both higher TCLo density (HR [per 0.01 ml-1 increase]: 1.18, 95% CI: 1.05-1.33, P = 0.005) and TCLo (HR: 1.69, 95% CI: 1.20-2.38, P = 0.002) were associated with shorter PFS. CONCLUSION: The previously suggested prognostic value of TCLo density was confirmed in this validation cohort. TCLo alone performed similarly well. Patients with high TCLo density (≥0.06 ml-1) or TCLo (>2) were at greater risk of GGR while on AS. With external validation, these metric may help guide risk-adapted surveillance protocols.

Is Regular Radiographic Upper Urinary Tract Imaging for Surveillance of Non-Muscle Invasive Bladder Cancer Justified?

Patients with non-muscle invasive (NMI) urothelial bladder cancer (BC) are at increased risk for the development of a secondary upper-urinary-tract urothelial carcinoma (UTUC). We aimed to assess the usefulness of routine upper-tract imaging surveillance during NMIBC follow-up in a patient cohort of a tertiary academic center. All routine upper-tract-imaging scans using computerized tomography urography (CTU) between 2003 and 2016 were assessed for UTUC detection. A total of 315 patients were analyzed. Initial tumor stage was Ta in 207 patients (65.7%), T1 in 98 patients (31.1%) and pure CIS in 10 patients (3.2%). A total of 149 (47.3%) presented with low-grade (LG), and 166 (52.7%) with high-grade (HG) disease. Median follow-up was 48 months (IQR: 55). Four patients (1.2%) were diagnosed with UTUC during follow-up. All four patients presented with initial Ta HG BC. Two of the patients (50%) were diagnosed by routine upper tract imaging. The other two patients were diagnosed after development of symptoms. The 5- and 10-year UTUC-free survival was 98.5% (standard error (SE) 0.9) and 97.6% (SE 1.3), respectively. UTUCs were detected exclusively in patients with initial HG disease, indicating that upper-tract surveillance might only be necessary in these patients.

Modified immunoscore improves the prediction of progression-free survival in patients with non-muscle-invasive bladder cancer: A digital pathology study.

Tumour-infiltrating lymphocytes (TIL), known to be of prognostic value in various solid tumours, have been in the focus of research in the last years. TIL are often quantified via IMMUNOSCORE ® (IS), a scoring system based on TIL cell densities. Recent studies were able to replicate these findings for muscle-invasive bladder cancer (MIBC), however data regarding non-muscle-invasive bladder cancer (NMIBC) are scarce. This study aimed to evaluate the value of a modified Immunoscore (mIS) as a predictive marker for NMIBC prognosis using tissue-micro-arrays (TMAs). We analysed two TMAs containing 316 samples from 158 patients with NMIBC, stained for CD3, CD8, CD45RO and FOXP3. Stained TIL were captured by digital pathology, cumulated, averaged, and reported as density (stained cells per mm²). The mIS was then constructed based on density of all four immune-cell types. Clinical, pathological and follow-up data were collected retrospectively. Univariable and multivariable cox regression analysis was performed to assess the potential value of mIS as a predictor for progression free survival (PFS) and recurrence-free-survival (RFS). Patients within "European Organisation for Research and Treatment of Cancer" (EORTC) risk groups were further substratified in high mIS and low mIS subgroups. Finally log-rank test was used to compare the different survival curves. The median age in our cohort was 68 years (Interquartile Range (IQR): 60 - 76), and 117 (74%) patients were male. A total of 26 patients (16.5%) were classified as EORTC low risk, 45 (28.5%) as intermediate risk and 87 (55.1%) as high risk. Patients in the EORTC high risk group with low mIS showed a shorter PFS in comparison to high mIS (HR 2.9, CI 0.79 - 11.0, p=0.082). In contrast, no predictive potential regarding PFS was observed in intermediate or low risk groups. Furthermore, mIS was not able to predict RFS in any EORTC risk group. mIS could be utilized to predict prognosis more accurately in high-risk patients with NMIBC by identifying those with higher or lower risk of progression. Therefore, mIS could be used to allocate these highrisk patients to more streamlined follow-up or more aggressive treatment strategies.

Modified Immunoscore Improves Prediction of Survival Outcomes in Patients Undergoing Radical Cystectomy for Bladder Cancer-A Retrospective Digital Pathology Study.

To evaluate the prognostic value of a modified Immunoscore (mIS) in a cohort of bladder cancer (BC) patients undergoing radical cystectomy (RC), two tissue microarrays of 159 BC patients were immunohistochemically stained for CD3/CD8/FOXP3 and CD45RO to detect Tumor-Infiltrating Lymphocytes (TIL). To predict progression free survival (PFS) and cancer specific survival (CSS), a predictive model cumulatively incorporating all four components was constructed and labeled as mIS. Patients were stratified into two risk groups; "high mIS/favorable risk" and "low mIS/unfavorable risk". Kaplan-Meier analysis was used to test mIS within each American Joint Committee on Cancer (AJCC) stage group for BC. In a univariable cox regression analysis all single components used for mIS, showed a significant association with CSS. Patients with high mIS (all components) in the AJCC stage IIIa group additionally showed a significantly longer PFS (Hazard Ratio (HR): 2.7; p = 0.008) and CSS (HR: 3.5; p = 0.006) as compared to patients with low mIS. mIS is of prognostic value in BC patients undergoing RC and was able to stratify patients within AJCC stage IIIa and might thus serve as a prognostic marker to guide risk-adapted treatment or follow-up strategies after RC.

Long-Term Oncological Efficacy of Retroperitoneoscopic Radical Nephrectomy of Localized Renal Cell Cancer pT1-3 (≤12 cm).

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Uptake of re-resection in T1 bladder cancer: An interrupted population-based time series analysis among different groups of surgeons.

INTRODUCTION: A second transurethral resection of the bladder tumor (TURBT) within 2 - 6 weeks after initial TURBT is thought to have diagnostic, therapeutic, and prognostic benefits in T1 bladder cancer (BC). However, little is known about the real-world uptake of this guideline-endorsed intervention. We aimed (1) to measure re-resection rates over time, (2) to investigate if a guideline revision (April 2008) explicitly endorsing re-resection within 2 - 6 weeks in all T1 BC patients led to an increase in re-resection rates, and (3) to investigate the uptake among different groups of surgeons. METHODOLOGY: Province-wide BC pathology reports (January 2001 to December 2015; Ontario, Canada) were linked with health administrative data to (1) identify primary cases of T1 BC and to (2) ascertain whether these patients received re-resection. The resulting patients were then aggregated into quarterly time series and investigated by descriptive analysis, interventional autoregressive moving average (ARIMA) modeling, and Poisson regression analysis. RESULTS: A cohort of 7,373 patients was aggregated into a time series. We observed a linear increase in re-resection rates from 8.4% in 2001 to 28.3% in 2015. An actual effect of the guideline revision in April 2008 on re-resection rates could not be detected (P = 0.41). However, we observed a rather heterogeneous uptake behavior among different groups of surgeons. Specifically, female surgeons, more junior surgeons, high-volume surgeons, Canadian graduates, and surgeons without an academic affiliation were all independently more likely to re-resect their patients (all P-values < 0.05 in adjusted analysis). CONCLUSIONS: Re-resection rates in primary T1 BC increased between 2001 and 2015 in the province of Ontario regardless of the guideline revision in April 2008. Our study demonstrates that the uptake of this guideline-endorsed intervention varies among different groups of surgeons and therefore warrants further research to identify barriers to change that can be addressed by tailored interventions.

Detection of recurrences using serum miR-371a-3p during active surveillance in men with stage I testicular germ cell tumours.

BACKGROUND: MiR-371a-3p predicts the presence of a macroscopic non-teratomatous germ cell tumour (GCT). We hypothesised that miR-371a-3p can also detect recurrence during active surveillance (AS) of stage I GCT. METHODS: We prospectively collected serum samples of 33 men. Relative expression of serum miR-371a-3p levels was determined at each follow-up visit using real-time quantitative reverse transcription-polymerase chain reaction. RESULTS: Recurrence was detected using standard follow-up investigations in 10/33 patients (30%) after a median of 7 months. Directly after orchiectomy, miR-371a-3p levels were not elevated in any of the 15 patients with available post-orchiectomy samples. However, all ten recurring patients exhibited increasing miR-371a-3p levels during follow-up, while miR-371a-3p levels remained non-elevated in all but one patient without recurrence. MiR-371a-3p detected recurrences at a median of 2 months (range 0-5) earlier than standard follow-up investigations. CONCLUSIONS: MiR-371a-3p levels immediately post orchiectomy are not predictive for recurrences and unfortunately cannot support decision-making for AS vs. adjuvant treatment. However, miR-371a-3p detects recurrences reliably and earlier than standard follow-up investigations. If this can be confirmed in larger cohorts, monitoring miR-371a-3p could replace surveillance imaging in seminomatous GCT and reduce the amount of imaging in non-seminomatous GCT. Earlier detection of disease recurrence may also reduce the overall treatment burden.

Tumor Stent for Chronic Ureteral Obstruction: Which Are Predictors of Stent Failure?

Purpose: To identify predictors of UROSOFT® tumor stent failure. According to the manufacturer, this reinforced ureteral stent has a maximal dwell time of 6 months. Nonetheless, stent failure may reduce this maximal dwell time. Methods: All patients undergoing first-time UROSOFT tumor stent insertion in our institution between 2010 and 2018 were considered for this retrospective analysis. Primary endpoint was stent failure and defined as premature stent exchange or percutaneous nephrostomy insertion. The local ethics committee approved the study protocol (study ID: BASEC 2020-00175). Results: In total, 182 patients were available for analysis. Median age was 68 years. Causes for tumor stent placement were extrinsic ureteral obstruction in 144 patients (79%) and intrinsic obstruction in 38 patients (21%). Tumor stent failure-free survival estimates at 1, 2, 3, 4, and 5 months were 89%, 83%, 76%, 65%, and 52%, respectively. Patients with stent failure had significantly higher grade of hydronephrosis, higher urinary culture bacterial growth, higher serum white blood cell count, higher C-reactive protein, and lower estimated glomerular filtration rate at the time of reintervention, compared with patients who underwent regular stent exchange. Of all baseline and perioperative parameters, we found bilateral insertion, intrinsic ureteral obstruction, and urinary tract infection (UTI) at time of tumor stent insertion to be significant and independent predictors of stent failure (all p < 0.05). Conclusion: Despite a theoretical maximal dwell time of 6 months, ∼50% of all cases are subject to premature stent failure. Predictors of stent failure are bilateral insertion, intrinsic ureteral obstruction, and UTI at the time of tumor stent insertion. Preoperative antibiotic therapy may impact on stent failure rate.

Factors Associated with Re-Resection in T1 Bladder Cancer: Identifying Patients Who Do Not Receive Guideline-Concordant Care at the Population Level.

PURPOSE: Prior research has shown that concordance with the guideline-endorsed recommendation to re-resect patients diagnosed with primary T1 bladder cancer (BC) is suboptimal. Therefore, the aim of this population-based study was to identify factors associated with re-resection in T1 BC. MATERIALS AND METHODS: We linked province-wide BC pathology reports (January 2001 to December 2015) with health administrative data sources to derive an incident cohort of patients diagnosed with T1 BC in the province of Ontario, Canada. Re-resection was ascertained by a billing claim for transurethral resection within 2 to 8 weeks after the initial resection, accounting for system-related wait times. Multivariable logistic regression analysis accounting for the clustered nature of the data was used to identify various patient-level and surgeon-level factors associated with re-resection. P values <0.05 were considered statistically significant (2-sided). RESULTS: We identified 7,373 patients who fulfilled the inclusion criteria. Overall, 1,678 patients (23%) underwent re-resection. Patients with a more aggressive tumor profile and individuals without sufficiently sampled muscularis propria as well as younger, healthier and socioeconomically advantaged patients were more likely to receive re-resection (all p <0.05). In addition, more senior, lower volume and male surgeons were less likely to perform re-resection for their patients (all p <0.05). CONCLUSIONS: Only a minority of all patients received re-resection within 2 to 8 weeks after initial resection. To improve the access to care for potentially underserved patients, we suggest specific knowledge translation/exchange interventions that also include equity aspects besides further promotion of evidence-based instead of eminence-based medicine.

Oncological benefit of re-resection for T1 bladder cancer: a comparative effectiveness study.

OBJECTIVES: To quantify the real-world survival benefit of re-resection vs no re-resection in patients diagnosed with T1 bladder cancer (BC) at the population level. PATIENTS AND METHODS: Retrospective population-wide observational cohort study based on pathology reports linked to health administrative data. We identified patients who were diagnosed with T1 BC in the province of Ontario (01/2001-12/2015) and used billing claims to ascertain whether they received re-resection within 2-10 weeks. The time-dependent effect of re-resection on survival outcomes was modelled by Cox proportional hazards regression (unadjusted and adjusted for numerous assumed patient- and surgeon-level confounding variables). Effect measures were presented as hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We identified 7666 patients of which 2162 (28.7%) underwent re-resection after a median (interquartile range) time of 45 (35-56) days. Patients who received re-resection were less likely to die from any causes (HR 0.68, 95% CI 0.63-0.74, P < 0.001) and from BC (HR 0.66, 95% CI 0.57-0.76, P < 0.001) during any time of follow-up. After adjusting for all assumed confounding variables, re-resection was still significantly associated with a lower overall mortality (HR 0.88, 95% CI 0.81-0.95, P < 0.001), while the association with cancer-specific survival marginally lost its statistical significance (HR 0.87, 95% CI 0.75-1.02, P = 0.08). CONCLUSIONS: A second transurethral resection within 2-6 weeks after the initial resection (i.e. re-resection) is recommended for patients diagnosed with primary T1 BC as prior studies suggest therapeutic, diagnostic, and prognostic benefits. However, results on survival endpoints are sparse, conflicting, and often affected by various biases. To the best of our knowledge, the present population-wide study represents the largest cohort of patients diagnosed with T1 BC and provides real-world evidence supporting the utilisation of re-resection in this group of patients.

En Bloc Resection of Bladder Tumor-Is It the Way Forward?

Transurethral resection of bladder tumors (TURBT) represents the cornerstone in diagnosis and treatment of bladder cancer but recurrence is observed in up to 80% and over- or understaging with TURBT is common. A more recent development to overcome these limitations represents en-bloc resection of bladder tumors (ERBT) which offers several advantages over TURBT. In this report, we briefly review studies assessing outcomes of bladder cancer patients undergoing ERBT. Most randomized and non-randomized trial demonstrate improvement in clinical outcomes for ERBT over TURBT, however more pathological and translational studies are warranted.

Assessment of Diagnostic Yield of Cystoscopy and Computed Tomographic Urography for Urinary Tract Cancers in Patients Evaluated for Microhematuria: A Systematic Review and Meta-analysis.

Importance: Microhematuria (MH) is a common finding that often leads to further evaluation for urinary tract cancers. There is ongoing debate about the extent to which patients with MH should be evaluated for cancer. Objective: To assess the diagnostic yield for detection of urinary tract cancers, specifically bladder cancer, upper tract urothelial carcinoma (UTUC), and kidney cell carcinoma, among patients evaluated for MH using cystoscopy and computed tomographic (CT) urography. Data Sources: MEDLINE, Scopus, and Embase were systematically searched for eligible studies published between January 1, 2009, and December 31, 2019. Study Selection: Original prospective and retrospective studies reporting the prevalence of cancer among patients evaluated for MH were eligible. Two authors independently screened the titles and abstracts to select studies that met the eligibility criteria and reached consensus about which studies to include. Among 5802 records identified, 5802 articles were screened using titles and abstracts. After exclusions, 55 full-text articles were assessed for eligibility, with 39 studies selected for systematic review. Data Extraction and Synthesis: This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Studies were quantitatively synthesized using a random-intercept logistic regression model. Main Outcomes and Measures: The primary outcome was diagnostic yield, defined as the proportion of patients with a diagnosis of urinary tract cancer (bladder cancer, UTUC, or kidney cell carcinoma) after presentation with MH. Studies were stratified by the percentage of cystoscopy and CT urography use and by high-risk cohorts. The diagnostic yields of CT urography and cystoscopy were calculated for each cancer type. Results: A total of 30 studies comprising 24 366 patients evaluated for MH were included in the meta-analysis. The pooled diagnostic yield among all patients was 2.00% (95% CI, 1.30%-3.09%) for bladder cancer, 0.02% (95% CI, 0.0%-0.15%) for UTUC, and 0.18% (95% CI, 0.09%-0.36%) for kidney cell carcinoma. Stratification of studies that used cystoscopy and/or CT urography for 95% or more of the cohort produced diagnostic yields of 2.74% (95% CI, 1.81%-4.12%) for bladder cancer, 0.09% (95% CI, 0.01%-0.75%) for UTUC, and 0.10% (95% CI, 0.04%-0.23%) for kidney cell carcinoma. In high-risk cohorts, the diagnostic yields increased to 4.61% (95% CI, 2.34%-8.90%) for bladder cancer and 0.45% (95% CI, 0.22%-0.95%) for UTUC. Conclusions and Relevance: This study's findings suggest that, given the low diagnostic yield of CT urography and the associated risks and costs, limiting its use to high-risk patients older than 50 years is warranted. Risk stratification, as recommended by the recent American Urology Association guidelines on MH, may be a better approach to tailor further evaluation.