Oncolytic adenoviral therapy plus pembrolizumab in BCG-unresponsive non-muscle-invasive bladder cancer: the phase 2 CORE-001 trial.

Cretostimogene grenadenorepvec is a serotype-5 oncolytic adenovirus designed to selectively replicate in cancer cells with retinoblastoma pathway alterations, previously tested as monotherapy in bacillus Calmette-Guérin (BCG)-experienced non-muscle-invasive bladder cancer. In this phase 2 study, we assessed the potential synergistic efficacy between intravesical cretostimogene and systemic pembrolizumab in patients with BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ (CIS). Thirty-five patients were treated with intravesical cretostimogene with systemic pembrolizumab. Induction cretostimogene was administered weekly for 6 weeks followed by three weekly maintenance infusions at months 3, 6, 9, 12 and 18 in patients maintaining complete response (CR). Patients with persistent CIS/high-grade Ta at the 3-month assessment were eligible for re-induction. Pembrolizumab was administered for up to 24 months. The primary endpoint was CR at 12 months as assessed by cystoscopy, urine cytology, cross-sectional imaging and mandatory bladder mapping biopsies. Secondary endpoints included CR at any time, duration of response, progression-free survival and safety. The CR rate in the intention-to-treat population at 12 months was 57.1% (20 out of 35, 95% confidence interval (CI) 40.7-73.5%), meeting the primary endpoint. A total of 29 out of 35 patients (82.9%, 95% CI 70.4-95.3%) derived a CR at 3 months. With a median follow-up of 26.5 months, the median duration of response has not been reached (95% CI 15.7 to not reached). The CR rate at 24 months was 51.4% (18 out of 35) (95% CI 34.9-68.0%). No patient progressed to muscle-invasive bladder cancer in this trial. Adverse events attributed to cretostimogene were low grade, self-limiting and predominantly limited to bladder-related symptoms. A total of 5 out of 35 patients (14.3%) developed grade 3 treatment-related adverse effects. There was no evidence of overlapping or synergistic toxicities. Combination intravesical cretostimogene and systemic pembrolizumab demonstrated enduring efficacy. With a toxicity profile similar to its monotherapy components, this combination may shift the benefit-to-risk ratio for patients with BCG-unresponsive CIS. ClinicalTrials.gov Identifier: NCT04387461 .

A rare case of inflammatory myofibroblastic tumor of the bladder with local invasion of the cervix and right ovary.

Inflammatory myofibroblastic tumors (IMT) are rare spindle cell neoplasms derived from mesenchymal cells. Primary genitourinary IMTs share morphological and molecular features with various malignant spindle cell sarcomas, which introduces a diagnostic challenge. We present the case of a 50-year-old female who was referred for evaluation of hematuria and nonspecific urinary symptoms and was found to have a mass originating from the urinary bladder that involved the cervix and right ovary. Transurethral resection of bladder tumor (TURBT) and immunohistochemical analysis revealed an IMT. To our knowledge, this is the first documented case of primary genitourinary IMT with cervical and ovarian involvement.

Adenocarcinoma of the Rete Testis: A Case Report.

Adenocarcinoma of the rete testis is an extremely rare and aggressive tumor that carries a poor prognosis. Successful long-term treatment for such tumors remains elusive as more cases are discovered worldwide. Treatment typically involves radical orchiectomy, retroperitoneal pelvic lymph node dissection, adjuvant chemotherapy, and/or continued surveillance. Here we describe the case of a 42-year-old male with a history of low testosterone who presented with a localized adenocarcinoma of the left rete testis. He was treated with radical orchiectomy and continued surveillance alone due to a lack of evidence of metastasis on follow-up imaging. History, prognosis, diagnostics, and treatment guidelines, as well as the most significant recent cases since the last rete testis adenocarcinoma literature meta-analysis, are discussed.

Renal Schwannoma: A Rare Case Report and Literature Review.

Schwannomas originating in the kidney are extremely rare with very few cases documented in the literature. It is difficult to distinguish them from other common renal masses based on clinical symptoms and imaging characteristics alone, as both are non-specific for this pathology. Thus, the final diagnosis of schwannoma is typically made only after surgical resection and histologic examination. We present the case of a 66-year-old female who was initially evaluated for flank pain and referred to us after a renal mass was found on CT imaging. A partial nephrectomy was performed, and subsequent pathological examination confirmed the diagnosis of renal schwannoma.

Urologic Manifestations and Hydronephrosis as Initial Presentation of Erdheim-Chester Disease: A Rare Form of Non-Langerhans Histiocytosis.

Erdheim-Chester disease (ECD) is a rare non-Langerhans histiocytosis that is classified as a malignancy of myeloid progenitor cells, with only 1,000 confirmed cases in the literature so far. It often manifests as a multi-system disorder with an initial presentation predominantly in the long bones, central nervous system (CNS), and retroperitoneal space, sometimes causing urologic symptoms as a result. ECD often presents indolently and in a spectrum of different ways, making it challenging to identify and treat. We report a case of a 63-year-old female with ECD that first presented with abdominal pain and acute renal injury due to ECD-related retroperitoneal fibrosis. We also explore the literature at large around ECD, its diagnosis, pathophysiology, and advances in treatments.

Occult Nodal Metastases in Patients Down-Staged to Nonmuscle Invasive Disease Following Neoadjuvant Chemotherapy.

OBJECTIVES: To evaluate the risk of occult nodal metastasis in patients with muscle invasive bladder cancer who exhibit a complete or partial clinical response to neoadjuvant chemotherapy (NAC) and assess a potential role for "bladder sparing" management given that the gold standard treatment, radical cystectomy (RC), is associated with high morbidity. METHODS: We queried the National Cancer Database for bladder cancer from 2004 to 2013 including patients with cT2-4aN0M0 bladder cancer who underwent multiagent NAC followed by RC and pelvic lymphadenectomy and excluding patients with nonurothelial predominant histology and those undergoing partial cystectomy. Student's t test was used to evaluate patients' demographics, presence of co-morbid conditions, and pathologic findings, notably the presence of lymphovascular invasion and variant histology. RESULTS: We identified 17,917 patients who underwent RC. Of these, 14.9% (n = 2673) received NAC before RC. About 13.1% and 14.5% of patients had complete (ypT0) and partial (ypTa, Tis, and T1) pathologic response, respectively. These 14.7% of cT2, 9.0% of cT3, and 6.9% of cT4 patients exhibited pT0 status on final pathology. And 4.9% of complete and 5.4% of partial responders demonstrated occult nodal metastases. Age, sex, ethnicity, the presence of co-morbidities, LVI, and variant histology were not significantly associated with occult nodal metastasis. CONCLUSION: While bladder preservation may be a viable option in patients who are carefully selected and closely followed after NAC, patients undergoing NAC may be at risk of occult disease outside of the bladder despite an otherwise clinical complete response diagnosed with cross-sectional imaging, cystoscopy, TURBT, and cytology.

National Practice Patterns and Overall Survival After Adjuvant Radiotherapy Following Radical Cystectomy for Urothelial Bladder Cancer in the USA, 2004-2013.

BACKGROUND: Adjuvant radiation therapy (ART) after radical cystectomy (RC) for urothelial bladder cancer (UBC) may play a role in the management of muscle-invasive BC, particularly in patients with locally advanced disease and adverse pathologic features (pT3/4 or positive surgical margins [PSMs]). Evidence regarding the effect of ART on overall survival (OS) is lacking. OBJECTIVE: To evaluate national practice patterns for the use of ART and assess its impact on OS for patients with adverse pathologic features (APF) after RC. DESIGN, SETTING, AND PARTICIPANTS: Using the National Cancer Data Base, we analyzed all UBC cases with APF after RC from 2004 to 2013. Patients were divided into ART and no-ART groups. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Relationships with oncological outcomes were analyzed using multivariable Cox regression and log-rank analyses. RESULTS AND LIMITATIONS: Use of ART decreased during the study period from 3.1% in 2004 to 1.7% in 2013 (p=0.03). ART was administered in 1.4%, 4.0% and 5.2% of patients with pT3 UBC, pT4 UBC, and PSMs (any pT stage), respectively. The rate of ART was significantly higher among younger ages, female sex, low-volume hospitals, nonacademic community care centers, higher stages, PSMs, perioperative chemotherapy, and lymph node-positive disease. Predictors of ART receipt were PSMs (odds ratio [OR] 3.4; p<0.0001), pT4 (OR 2.6; p=0.02), community based centers (OR 2.1; p<0.0001), and female sex (OR 1.8; p<0.0001). Risk factors for worse OS included age, higher tumor stage and comorbidities, PSMs, positive nodes, and suboptimal lymph node dissection (<10 nodes removed; all p<0.001). ART was not independently associated with better OS in the full cohort (p=0.54). However, subgroup analyses suggested an OS benefit for patients with PSMs (hazard ratio 0.73; p=0.047). Limitations include the retrospective design and limited details regarding cancer-specific survival. CONCLUSIONS: Use of ART for APF following RC is not common in the USA and the rate of ART has been decreasing over time. ART may have an OS benefit after RC for patients with PSMs. PATIENT SUMMARY: In this report we looked at the outcomes for patients with locally advanced bladder cancer receiving adjuvant radiation therapy following cystectomy in a large US population. We found that adding radiation therapy after removing the bladder cancer may have some survival benefits for patients with positive surgical margins.

Assessing the Impact of Time to Cystectomy for Variant Histology of Urothelial Bladder Cancer.

OBJECTIVE: To determine if the timing of radical cystectomy for variant histology of urothelial carcinoma has an impact on survival. Variant histology has been associated with aberrant behavior compared to pure urothelial carcinoma, however the timing of surgery for these patients has not been studied. MATERIALS AND METHODS: We identified 363 patients with cT2-T4N0M0 urothelial carcinoma who underwent radical cystectomy without perioperative intravesical and/or systemic therapy from 2003 to 2014. Clinicopathologic data were compared between pure urothelial carcinoma and variant histology. The time from diagnosis to radical cystectomy was analyzed as a continuous variable and dichotomized at 4-, 8-, and 12-weeks to determine impact on oncologic outcomes. RESULTS: Patients with variant histology, when compared to those with pure urothelial carcinoma, were more likely to present with extravesical disease (P <.01), be upstaged (P <.01), have lymphovascular invasion (P <.01) and have lymph node metastasis at radical cystectomy (P = .02). The median days to radical cystectomy did not differ between pure urothelial and variant histology. On multivariable analysis controlling for age, comorbidities, tumor stage, lymph node status, lymphovascular invasion, and surgical margins, every month in delay was associated with a worse overall survival for variants (HR = 1.36, P = .003). At an 8-week delay or longer, those with variant histology had a statistically worse survival (P = .03). CONCLUSION: For patients with variant histology, delays in surgery were associated with an increased risk of death.

Socioeconomic and insurance status are independent prognostic indicators of higher disease stage and worse prognosis in bladder cancer.

OBJECTIVES: Bladder cancer is the fourth most common cancer among males and poses a significant financial burden, yet there are no large-scale studies focused on the correlation between socioeconomic (SES) and insurance status and bladder cancer outcomes. The objective of this study was to determine the effect of SES and insurance type on outcomes in bladder cancer. MATERIALS AND METHODS: A population-based search was performed using the National Cancer Institute's Surveillance, Epidemiology, and End Results 18 database. Patients aged 18 or older and diagnosed with bladder cancer between 2011 and 2015 were identified. Data on patient demographics, SES features, insurance status, tumor characteristics, and survival were collected. A county-level SES measure was created in a method consistent with prior literature. Primary outcomes were overall survival (OS) and disease-specific survival (DSS). RESULTS: A total of 91,308 patients were identified. Factors predictive of having muscle invasive disease included having Medicaid insurance, having no insurance, and being in the lowest SES quartile (all P < 0.001). Having Medicaid or no insurance was predictive of having node positive or metastatic disease (P < 0.001). Independent of T stage, patients in the lowest and second lowest SES quartiles had worse OS (P = 0.004 and P = 0.022, respectively) and DSS (P < 0.001 for both). Patients with Medicaid or no insurance had worse OS and DSS (P < 0.001 for all). CONCLUSIONS: Lower SES status, Medicaid insurance, and having no insurance were all predictive of having higher tumor stage. Independent of tumor stage, being of lower SES, having Medicaid insurance, and having no insurance predicted worse OS and DSS.

Correction to: Enhanced Endoscopy in Bladder Cancer.

Author Siamak Daneshmand would like to note that this article published in Current Urology Reports inadvertently did not disclose financial information that could possibly be a conflict of interest.

Testicular Mesothelioma: An Analysis of Epidemiology, Patient Outcomes, and Prognostic Factors.

OBJECTIVES: To characterize demographic features, clinical characteristics, and oncologic outcomes of mesothelioma of the testis. METHODS: A population based search was performed using the National Cancer Institute's SEER 18 database. Patients diagnosed with malignant mesothelioma of the male genital organs from 1973 to 2015 were identified. Data on patient age, race, tumor laterality, histologic subtype, tumor extent, tumor size, tumor grade, treatment, cause of death, and survival months was collected. Primary outcomes were overall survival (OS) and disease-specific survival (DSS). RESULTS: A total of 113 patients with testicular mesothelioma were identified. The 5-year OS and DSS for all patients was 49% and 58%, and the 10-year OS and DSS was 33% and 45%, respectively. Biphasic mesotheliomas were associated with worse OS compared to general mesotheliomas and epithelioid subtypes (P = .043 and P = .039, respectively). Median survival time was not reached in patients with T1 disease while OS was 1.7 years and DSS was 1.8 years for patients with T4 disease (OS P = .002, DSS P <.001). Tumors greater than or equal to 4 cm were associated with worse OS and DSS (OS P = .025, DSS P = .047). CONCLUSION: This rare malignancy has significant mortality, with poor survival associated with biphasic subtypes, higher disease stage, and a critical tumor size cutoff of 4 cm.

Assessing trends in urinary diversion after radical cystectomy for bladder cancer in the United States.

OBJECTIVES: We assessed recent trends in both urinary diversion after radical cystectomy for bladder cancer in the United States and patient- and hospital-related characteristics. We also identified variables associated with undergoing continent diversion. MATERIALS AND METHODS: We queried the National Cancer Database and identified 27,170 patients who underwent radical cystectomy with urinary diversion from 2004 to 2013. Patient demographics, socioeconomic variables, and hospital-related factors were compared between incontinent and continent diversion and trended over time. Multivariable logistic regression was used to identify variables associated with undergoing continent diversion. RESULTS: Overall, 23,224 (85.5%) and 3,946 (14.5%) patients underwent incontinent and continent diversion, respectively. Continent diversion declined from 17.2% in 2004 to 2006 to 12.1% in 2010 to 2013 (P < 0.01). When analyzing high-volume facilities, those performing ≥75% minimally invasive radical cystectomy had fewer continent diversions (10.2%) compared to centers with higher rate of open approach (19.7%), P < 0.01. Higher income, facility located in the West, academic programs, high-volume facilities, and patients traveling >60 miles for care were significantly associated with undergoing continent diversion. Rate of continent diversion has declined in most patient- and hospital-related subgroups. Compared to 2004 to 2006, patients in 2010 to 2013 were more likely to be older, have more comorbidities, and be operated on at a high-volume academic facility. CONCLUSION: The rate of continent diversion has declined to 12.1% in the United States. Hospital volume and type, patient income, distance traveled for care, and geography are significantly associated with undergoing continent diversion. Even among high-volume and academic centers, the rate of continent diversion is declining.

Enhanced Endoscopy in Bladder Cancer.

PURPOSE OF REVIEW: Endoscopy coupled with targeted resections represents a cornerstone in the diagnosis, staging, and treatment of patients with bladder cancer. Direct visualization can be challenging and imprecise due to patient-, tumor-, and surgeon-specific factors. We will review contemporary endoscopic technologies and techniques used to improve our ability to safely identify and resect malignant lesions in patients with bladder cancer. RECENT FINDINGS: Enhanced endoscopic imaging technology may improve detection rates for bladder cancer throughout the upper and lower urinary tract, which may lead to improvements in recurrence and progression rates for non-muscle invasive bladder cancer (NMIBC). New techniques including narrow-band imaging (NBI), photodynamic diagnosis (PDD), Storz Professional Image Enhancement System (SPIES), optical coherence tomography (OCT), and others have shown benefit and may further improve our ability to detect and stage bladder tumors. Enhanced endoscopy technologies have already demonstrated value in improving the sensitivity of bladder cancer detection and early results suggest they may improve short- and long-term oncologic outcomes.

Indications, evolving technique, and early outcomes with robotic retroperitoneal lymph node dissection.

PURPOSE OF REVIEW: Examine and discuss indications, technique, and outcomes for robotic retroperitoneal lymph node dissection (RPLND) for testicular cancer. RECENT FINDINGS: Open RPLND has been the longstanding standard of care for both primary and post chemotherapy RPLND. Recently, robotic RPLND has been an attractive option with the intent of reducing the morbidity associated with open surgery while providing identical oncologic efficacy. Naysayers of robotic RPLND suggest it is often inappropriately used as a staging procedure and consequently can compromise oncologic efficacy. SUMMARY: Robotic RPLND is being evaluated as a therapeutic equivalent to open RPLND. On the basis of limited published data with modest follow-up from experienced centers, robotic RPLND appears to provide effective staging and therapeutic data mirroring that of open surgery.

Perioperative and long-term outcomes after radical cystectomy in hemodialysis patients.

PURPOSE: Patients on hemodialysis have an increased risk of developing advanced stage bladder cancer. They also have a significant risk of noncancer-related mortality. Radical cystectomy (RC) is the standard of care for nonmetastatic muscle-invasive bladder cancer, however little is known regarding outcomes in this population. MATERIALS AND METHODS: The United States Renal Disease System database was used to identify all patients on hemodialysis who underwent RC for bladder cancer in the United States between 1984 and 2013. A total of 985 patients were identified for analysis. Perioperative outcomes were evaluated. Competing risks analysis was used to estimate overall and cancer-specific mortality along with factors associated with death. RESULTS: Median hospital length of stay was 10 days and 43.1% of patients experienced a complication. Mortality within 30 days was 9.3%. Overall mortality at 1, 3, and 5 years was 51.7%, 77.3%, and 87.9%, respectively. Cancer-specific mortality at 1, 3, and 5 years was 12.3%, 18.4%, and 19.7%, respectively. Age, diabetes, and cerebrovascular disease were independently associated with overall mortality, while performance of urinary diversion was associated with a protective effect. Active smoking was the sole risk factor for cancer-specific mortality. CONCLUSIONS: RC in dialysis patients is associated with significant morbidity and mortality, with less than 15% overall survival at 5 years. Older patients, and those with a history of diabetes or cerebrovascular disease, are at an increased risk of mortality.

Continent Cutaneous Diversion.

Techniques in continent cutaneous urinary diversion (CCUD) have evolved significantly over the last 30 years resulting in several well-established procedures. CCUD is well suited for patients in whom the urethra cannot be used for orthotopic diversion due to preexisting incontinence, radiation damage, or malignancy. Reservoirs are constructed with adherence to basic principles of continent urinary diversion, including the use of detubularized bowel in a spherical conformation for pouch creation with either ileum or the right colon. The article reviews the history, patient selection, preoperative evaluation, surgical technique, and outcomes of CCUD.

Incidence, Risk Factors, and Outcomes for Rectal Injury During Radical Prostatectomy: A Population-based Study.

BACKGROUND: Rectal injury (RI) is a rare but potentially serious complication of radical prostatectomy (RP). Current evidence is limited owing to relatively small cohorts from select, tertiary referral centers. OBJECTIVE: To evaluate the incidence of and potential risk factors for RI during radical RP at a population level in the USA. DESIGN, SETTINGS, AND PARTICIPANTS: Using the National Inpatient Sample database (2003-2012), we identified patients with prostate cancer who underwent RP. Survey-weighted cohorts were created based on the diagnosis and repair of RI during initial hospitalization. Data included demographics, hospital characteristics, surgical details, complications, and perioperative outcomes. Multivariable logistic regression was used to identify risk factors for RI. RESULTS AND LIMITATIONS: Of 614 294 men who underwent RP, there were 2900 (0.5%) RIs, with a 26% decline from 2003-2006 to 2009-2012 (p<0.01). Patients with RI were slightly older (62.0 vs 61.2 yr; p<0.01) and more commonly of African ancestry (0.8% vs 0.4% Caucasians; p<0.01). RI was more common among patients with benign prostatic hyperplasia (BPH), metastatic disease, and low body mass index (BMI; p<0.05). The RI incidence was higher for open (0.6%) compared to laparoscopic (0.4%) and robotic RP (0.2%; p<0.01). RI was more common at rural (0.8% vs 0.5% urban), nonteaching (0.6% vs 0.4% teaching), and low-volume hospitals (0.6% vs 0.3% high-volume; p<0.01). Complication rates (28% vs 11%; p<0.01) and length of stay (4.8 vs 2.3 d; p<0.01) were greater in the RI group. Multivariable analysis identified African ancestry, BPH, and metastatic cancer as predictors of RI, while robotic approach, high-volume hospital, and obesity reduced the risk (p<0.05). CONCLUSIONS: RI during RP is a rare complication, but is more common among men with African ancestry and for procedures carried out using an open surgical technique or in low-volume hospitals, and among those with low BMI, BPH, or metastatic disease. PATIENT SUMMARY: In a large US population, we found that rectal injury (RI) is a rare complication of radical prostatectomy, and that the risk of RI can increase according to patient- and hospital-specific characteristics.

Impact of Perioperative Infection on Cancer Specific Survival after Nephrectomy for Renal Cell Carcinoma.

PURPOSE: Several case reports have documented rare spontaneous cancer regression following systemic infections. Immune related targeted therapies are now available for many cancers, including renal cell carcinoma. We hypothesized that perioperative infection after nephrectomy for renal cell carcinoma may impact long-term cancer specific survival. MATERIALS AND METHODS: We performed a retrospective cohort study using SEER (Surveillance, Epidemiology and End Results)-Medicare claims data from 2004 to 2011. ICD-9 and CPT codes were used to identify patients older than 65 years who underwent radical or partial nephrectomy for renal cell carcinoma. Patients hospitalized for infection within 30 days of surgery were identified. Study exclusion criteria included death within 90 days of surgery, immunodeficiency and metastatic disease at diagnosis. Kaplan-Meier curves were used to evaluate cancer specific survival between infection vs no infection groups. A Cox proportional hazards model was created to assess survival while controlling for age, gender, race, Elixhauser index, tumor grade, tumor size, histological subtype, AJCC (American Joint Committee on Cancer) stage, systemic therapy and geographic region. RESULTS: Of 8,967 patients 493 (5.5%) were hospitalized for infection after nephrectomy. Median age was 74 years (IQR 69-79), the mean ± SD Elixhauser index was 4.9 ± 7.4 and median followup was 42 months (IQR 22-67). Following nephrectomy univariable Cox regression showed a nonsignificant improvement in cancer specific survival in patients with a serious infection requiring hospitalization (HR 0.84, 95% CI 0.69-1.00, p = 0.054). Cox multivariable regression revealed significant improvement in cancer specific survival for the same population (HR 0.75, 95% CI 0.57-0.99, p = 0.04). This effect was primarily due to patients with larger (7 cm or greater) tumors (HR 0.67, 95% CI 0.44-0.99, p = 0.049). No impact was observed among patients with smaller (less than 7 cm) tumors (HR 0.82, 95% CI 0.57-1.19, p = 0.3). CONCLUSIONS: In patients with T2 (7 cm or greater) renal cell carcinoma who undergo nephrectomy perioperative infection may improve cancer specific survival.