The Dearth of Representation in FDA Approved Drug Trials.

The generalizability of data derived from randomized controlled trials is of paramount importance given their utility in the Food & Drug Administration (FDA) drug approval process. An essential part of this process is the inclusion of reliably reported gender, race and ethnicity data in trials that lead to FDA drug approval. Despite previous mandates by the FDA and Clinicaltrials.gov, gender and race-specific data remains under reported. We reviewed 100 most recently approved FDA medications, and abstracted the clinical trial data from Clinicaltrials.gov that supported their approval. We then compared these FDA approved trials to non-FDA approved trials from the same year and of similar size. We found that 40% of the FDA trials were missing race/ethnicity information, while 24% of these trials did not include gender information. We demonstrate that there remains a significant amount of missing gender and racial/ethnic data in trials that lead to FDA-approved medications.

The role of surgery for locally advanced urothelial cancers.

PURPOSE OF REVIEW: Extirpative surgery can play an important role in the management strategies for locally advanced urothelial carcinoma. The current review is intended to relay current information reported in the literature over the past 12 months regarding the usage of surgical resection in advanced urothelial cancers of the bladder and upper tracts, document operative outcomes, and oncologic efficacy. RECENT FINDINGS: Multimodal therapy is key to long-term overall survival for advanced urothelial carcinoma. Radical cystectomy with bilateral pelvic lymph node dissection can be performed after an observable response to chemotherapy or immunotherapy for cT4 or cN2 and higher node-positive disease of the bladder. Moreover, radical cystectomy after trimodal therapy similarly yields durable local response. For upper tract disease, nephroureterectomy with regional lymphadenectomy is the primary surgical modality used often in conjunction with perioperative cisplatin-based chemotherapy. SUMMARY: Surgical resection as a monotherapy is not curative in patients with locally advanced urothelial carcinoma. However, its use in combination with systemic agents can potentiate durable long-term survival in a subset of patients. Future studies investigating patient-reported outcomes among those receiving consolidative surgery for locally advanced disease are warranted to guide clinical recommendations.

RNA sequencing in a penile cancer cohort: an investigation of biomarkers of cisplatin resistance and potential therapeutic drug targets.

OBJECTIVE: Chemoresistance in distant micrometastatic lesions may account for diminished durable response rates in advanced penile cancer. However, there are limited studies on new therapeutic targets and the identification of biomarkers that predict chemotherapy response in this population. Thus, we examine the expression of candidate biomarkers of cisplatin resistance, ERCC1 and E2F1, and perform next-generation sequencing on the cancer transcriptome in a penile cancer cohort. MATERIALS AND METHODS: In this retrospective cohort study, we identified 71 patients treated for penile squamous cell carcinoma between 2009 and 2019. Immunohistochemistry staining for ERCC1 and E2F1 was performed. H-scores were measured for patient specimens obtained from adjacent normal skin, primary tumor and metastatic lymph node specimens and correlated with RNA expression data obtained through next-generation sequencing. RESULTS: Of the 71 patients identified, 51 and 8 had available surgical specimens for immunohistochemistry and RNA sequencing, respectively. Median H-scores for ERCC1 in adjacent normal skin, primary and metastatic tumors were 17.04, 3.15, and 7.9 respectively compared to E2F1 (43.95, 15.54, 7.9). The median H-score for E2F1 was higher in poorly differentiated primary tumors (24.86) compared to well (7.62) and moderately differentiated (9.55, p = 0.055). Next generation sequencing showed no difference in RNA expression of E2F1 nor ERCC1 between primary tumors and metastatic lesions however did demonstrate elevated RNA expression of genes such as MMP1, and MMP10 in primary tumors compared to adjacent normal skin. CONCLUSION: We identify potential drug targets for metastatic penile cancer through next-generation RNA sequencing.

Access and Representation: A Narrative Review of the Disparities in Access to Clinical Trials and Precision Oncology in Black men with Prostate Cancer.

OBJECTIVE: To provide commentary on the disparities in access to clinical trials and precision oncology specific to Black men with Prostate Cancer (PCa) in the United States and lend a general framework to aid in closing these gaps. MATERIALS AND METHODS: The ideas, commentaries and data presented in this narrative review were synthesized by utilizing qualitative and quantitative studies, reviews, and randomized control trials performed between 2010 and 2021. We searched PubMed using the key words "Medicaid", "Medicare", "clinical trials", "African Americans", "Black", "underrepresentation", "access", "Prostate Cancer", "minority recruitment", "racial disparities", "disparity", "genomics", "biomarkers", "diagnostic" "prognostic", "validation", "precision medicine", and "precision oncology" to identify important themes, trends and data described in the current review. Keywords were used alone and combination with both "AND" and "OR" terms. RESULTS: Black men with prostate cancer (PCa) in the United States have earlier onset of disease, present with more advanced stages, and worse prostate cancer-specific survival than their White counterparts. Potential causative factors vary from disparities in health care access to differences in tumor immunobiology and genomics along with disparate screening rates, management patterns and underrepresentation in clinical and translational research such as clinical trials and precision oncology. CONCLUSION: To avoid increasing the racial disparity in PCa outcomes for Black men, we must increase inclusion of Black men into precision oncology and clinical trials, using multilevel change. Underrepresentation in clinical and translational research may potentiate poorly validated risk calculators and biomarkers, leading to poor treatment decisions in high-risk populations. Relevant actions include funding to include minority-serving institutions as recruitment sites, and inclusion of evidence based recruitment methods in funded research to increase Black representation in clinical trials and translational research.

The association between sarcopenia and bladder cancer-specific mortality and all-cause mortality after radical cystectomy: A systematic review and meta-analysis.

Objective: To compare cancer-specific mortality (CSM) and all-cause mortality (ACM) between patients with and without sarcopenia who underwent radical cystectomy for bladder cancer. Materials and methods: We performed a systematic review and meta-analysis of original articles published from October 2010 to March 2019 evaluating the effect of sarcopenia on CSM and ACM. We extracted hazard ratios (HRs) and 95% confidence intervals (CIs) for CSM and ACM from the included studies. Heterogeneity amongst studies was measured using the Q-statistic and the I 2 index. Meta-analysis was performed using a random-effects model if heterogeneity was high and fixed-effects models if heterogeneity was low. Results: We identified 145 publications, of which five were included in the meta-analysis. These five studies represented 1447 patients of which 453 were classified as sarcopenic and 534 were non-sarcopenic. CSM and ACM were increased in sarcopenic vs non-sarcopenic patients (HR 1.64, 95% CI 1.30-2.08, P < 0.01 and HR 1.41, 95% CI 1.22-1.62, P < 0.01, respectively). Conclusions: Sarcopenia is significantly associated with increased CSM and ACM in bladder cancer. Identifying patients with sarcopenia will augment preoperative counselling and planning. Further studies are required to evaluate targeted interventions in patients with sarcopenia to improve clinical outcomes. Abbreviations: ACM: all-cause mortality; ASA: American Association of Anesthesiologists; BMI: body mass index; CCI: Charlson Comorbidity Index; CSM: cancer-specific mortality; CSS: cancer-specific survival; ECOG: Eastern Cooperative Oncology Group; HR: hazard ratio; NAC: neoadjuvant chemotherapy; NIH: National Institutes of Health; OS: overall survival; RC: radical cystectomy; RCT: randomised controlled trial; SMI: Skeletal Muscle Index.

National Trends and Impact of Regionalization of Radical Cystectomy on Survival Outcomes in Patients with Muscle Invasive Bladder Cancer.

OBJECTIVE: To evaluate national trends and the effect of surgical volume on perioperative mortality and overall survival (OS)in patients undergoing radical cystectomy (RC) for muscle invasive bladder cancer (MIBC). METHODS: We investigated the National Cancer Database to identify patients with localized MIBC (cT2a-T4, M0) who underwent RC from 2004 to 2014. Demographics, 30- and 90-day mortality rates, as well as OS were analyzed. Hospitals were stratified into low-, medium-, and high-volume centers according to median number of RCs performed per year. Multivariate logistic regression models were fitted to identify independent predictors of perioperative mortality. Kaplan-Meier survival curves were generated to evaluate OS. Cox proportional hazard modeling was performed to identify independent predictors of OS. RESULTS: A total of 24,763 patients with localized MIBC who underwent RC from 2004 to 2014 were included in the study. Overall, most (70.85%) RCs occurred at low-volume hospitals, whereas only 15.83% were performed at high-volume hospitals. Thirty-day mortality rates were 2.87%, 2.19%, and 1.83% (P < .01); and 90-day mortality rates were 8.25%, 6.9%, and 5.9% (P < .01) at low-, medium-, and high-volume hospitals, respectively. Multivariate analyses identified RC volume as an independent predictor of 30- and 90-day mortality. RC in high-volume hospitals was associated with a 35% risk reduction in 30-day mortality (odds ratio 0.65, 95% confidence interval [CI] 0.49-0.85; P < .01), and a 26% risk reduction in 90-day mortality (0.74, 95% CI, 0.63-0.87; P < .01). CONCLUSIONS: Treatment at high-volume centers offers improved outcomes and OS benefit. However, in the United States, only 16% of RCs are performed in high-volume hospitals.

Impact of Retained Ureteral Stents on Long-Term Renal Function.

INTRODUCTION: The current literature does not provide any data regarding the rate of chronic kidney disease associated with retained ureteral stents. Thus, we determined the rates of major morbidities such as chronic kidney disease and severe urinary tract infection caused by retained stents. METHODS: We retrospectively reviewed all records of patients at our institution who underwent ureteral stent placement and ureteral stent removal between January 2003 and October 2016. Of these patients 34 were diagnosed with a retained ureteral stent defined as a stent in place for more than 6 months. We selected 120 patients with a nonretained stent during this time frame to serve as a control group. Our primary end point was the rate of chronic kidney disease after ureteral stent removal. RESULTS: Median duration of ureteral stent in situ was 13.7 months (range 6.4 to 146.1) in the retained group vs 32 days (range 2 days to 5.1 months) in the control group. Of the retained group 9 patients (26.47%) with normal renal function before stent placement were diagnosed with chronic kidney disease after stent removal vs 4 (3.33%) in the control group (OR 8.64, 95% CI 2.05-41.9, p = 0.0009). CONCLUSIONS: Patient counseling and measures to ensure compliance with followup are of paramount importance after stent placement as patients with a retained ureteral stent are at risk for chronic kidney disease despite removal of the retained stent.

Candida glabrata: A Unique Cause of Necrotizing Urethritis.

Necrotizing urethritis is a rare malady with only one other case reported in the literature found to be due to an infectious cause. We report a case of necrotizing urethritis caused by Candida glabrata and review all relevant literature to date. The patient is a 56-year-old man with a past medical history significant for poorly controlled insulin-dependent type 2 diabetes mellitus and incomplete bladder emptying who presented to the University Medical Center with perineal pain, fever, and urinary retention. Cross-sectional imaging showed emphysematous changes in the bulb of the corpus spongiosum. After admission, his fever and leukocytosis persisted, and his physical exam worsened with intravenous antibiotics alone. Subsequently, the patient underwent cystourethroscopy with incision and debridement of the corpus spongiosum. Postoperatively, he improved clinically and his spongiosum wound and urine grew Candida glabrata. To our knowledge, we report the first case of necrotizing urethritis caused by Candida glabrata.

Renal medullary carcinoma with an ophthalmic metastasis.

Renal medullary carcinoma (RMC) is a rare, aggressive primary renal malignancy that classically occurs in adolescent males with sickle cell trait and universally presents with metastatic disease at presentation. We report a case of medullary carcinoma in a young man with likely ophthalmic metastasis. We also review relevant literature available to date. The patient is a 20-year-old African-American male with a past medical history significant to for sickle cell trait who presented to the University Medical Center with cough and the right eye pain for 1 month as well as painless gross hematuria for 1 week. A chest and abdominal computed tomography showed a 7 cm hypodense right renal mass with bilateral hilar adenopathy, and multiple bilateral pulmonary nodules. A renal biopsy was performed and showed RMC. Ophthalmic exam revealed the right retinal hemorrhage concerning for a metastatic lesion. Palliative chemotherapy was offered to the patient, however, he and his family chose to enroll in hospice care considering his poor prognosis. He subsequently passed away 33 days after presentation. To our knowledge, there is only one other case of ophthalmic metastasis in a patient with metastatic RMC. Thus, we present this case to contribute to current literature regarding orbital metastasis in this largely fatal disease.

Association of prostate volume with incidence and aggressiveness of prostate cancer.

OBJECTIVE: The aim of this study was to investigate the possible correlation between prostate volume and aggressiveness and incidence of prostate cancer (PCa). PATIENTS AND METHODS: A chart review of a cohort of 448 consecutive prostate biopsy-naive men was performed. These men underwent at least a 12-core biopsy at our institution due to increased prostate-specific antigen serum levels (>4 ng/mL) and/or suspicious findings on digital rectal examination during the period between 2008 and 2013. Transrectal ultrasound was used to determine the prostate volume. RESULTS: The positive biopsy rate was 66% for patients with a prostate volume of ≤35 cc and 40% for patients with a prostate volume of ≥65 cc (P<0.001). Of the 110 patients testing positive on biopsy with a volume of ≤35 cc, 10 patients (9.1%) had a Gleason score of ≥8. Of the 27 patients testing positive on biopsy with a volume of ≥65 cc, only 1 patient (3.7%) had a Gleason score of ≥8. CONCLUSION: These results suggest that there may be an association between prostate volume and the incidence and aggressiveness of PCa. The larger the prostate, the lower the positive biopsy rate for PCa and the lower the Gleason score.

A 55-Year-Old Man with Stage IV Squamous Cell Carcinoma of the Right Groin after External Beam Radiation for Testicular Cancer.

Treating testicular cancer with adjuvant radiation has been associated with a number of second malignancies affecting the genitourinary tract and retroperitoneal structures; however, there have been few reported cases of cutaneous second malignancies. We report the case of a man who developed stage IV squamous cell carcinoma (SCC) of a condyloma after orchiectomy and adjuvant radiation for testicular cancer. We also review relevant literature available to date. A 55-year-old Caucasian man presented to the hospital with a large growth at the right groin which had grown into his right thigh preventing ambulation. His past medical history was significant for right testicular cancer of unknown pathology treated with orchiectomy and adjuvant radiation twenty years ago. Punch biopsy of the lesion revealed superficially invasive squamous cell carcinoma. He underwent excision of the growth with subsequent Cisplatin, radiation boost, and Paclitaxel regimens. Despite an aggressive treatment regimen and an initial good response, the patient's cancer progressed requiring palliative care. It is unclear whether or not therapeutic radiation in this case promoted the conversion of the patient's condyloma to a malignant lesion. Further studies are required at this time to clarify the clinical implications of these findings.