Protocol for Phase I Study of Pembrolizumab in Combination with Bacillus Calmette-Guérin for Patients with High-Risk Non-Muscle Invasive Bladder Cancer

INTRODUCTION: The initial treatment for high-risk non-muscle invasive bladder cancer (NMIBC) is endoscopic resection of the tumour followed by BCG therapy. In those who develop recurrence, the standard treatment is radical cystectomy. Despite the advancement in surgical technique and postoperative care, the degree of morbidity associated with radical cystectomy remains high, therefore less invasive treatment modalities are desirable. Therapies targeting the programmed death (PD) pathway have shown promise in urothelial carcinoma. We undertook the current study to determine the safety and efficacy of administering pembrolizumab (a monoclonal antibody targeting the interaction between PD-1 and its ligand) in combination with BCG in high-risk NMIBC. METHODS: This is a single-centre phase I safety and efficacy study of pembrolizumab used in combination with intravesicular BCG treatment for subjects with pathologically documented high-risk NMIBC despite having received two courses of induction therapy or BCG treatment followed by maintenance BCG. Fifteen subjects will be enrolled, patients will receive treatment with 200 mg of pembrolizumab every 21 days, starting 2 weeks from the initial endoscopic resection and continuing for 6 weeks after the final dose of BCG. The primary objective is to determine the safety of administering pembrolizumab at a fixed dose of 200 mg every 3 weeks in conjunction with intravesicular BCG treatment in patients with high-risk NMIBC who have failed previous treatment. Secondary objectives are to determine the 19 weeks and the 3, 12 and 24 months post-treatment completion complete response rate with combined pembrolizumab and intravesicular BCG therapy in the aforementioned patients. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Review Board of the Henry Ford Hospital. The results of this study will be published in a peer-reviewed journal and presented at a scientific conference. TRIAL REGISTRATION NUMBER: NCT02324582

Pseudosarcomatous myofibroblastic proliferations of the genitourinary tract are genetically different from nodular fasciitis and lack USP6, ROS1 and ETV6 gene rearrangements

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145266/1/his13526_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145266/2/his13526.pd

Pyeloduodenal fistula complicating neoadjuvant chemotherapy in a patient diagnosed with muscle invasive bladder cancer.

A 72-year old male presented with muscle invasive bladder cancer was counseled on the standard of care neoadjuvant chemotherapy and he started treatment. He then presented with anemia, blood in the stool and gas in the right renal pelvis and was diagnosed with Pyeloduodenal fistula. The fistula was treated with clipping by gastroenterology and the bladder tumor treated with robotic partial cystectomy

Phase I Trial of Safety of Combining BCG with Pembrolizumab in Patients with High Grade Superficial Bladder Cancer Unresponsive to Previous Intravesical Therapy

Background: Bacille Calmette-Guerin (BCG) is the most effective agent in the treatment of high grade superficial bladder cancer (HGSBC); however, not all patients respond to BCG, and recurrent disease is associated with a poor prognosis. The blockade of immune checkpoints of the pathway involving programmed death 1 (PD1) has been shown recently to be effective in cancer therapy. We started the first trial in the United States to combine an anti-PD1 drug (pembrolizumab) with BCG therapy in patients with HGSBC. Methods: The primary objective of the study was to determine the safety of administering a 200 mg fixed dose of pembrolizumab in conjunction with intravesical BCG treatment in HGSBC patients who have failed two courses of induction therapy or one course of BCG induction therapy followed by maintenance therapy. Patients included had to have pathologically documented HGSBC (Ta, T1) at time of restaging, or have pathologically documented high grade CIS of the bladder at time of initial resection for recurrent/persistent bladder cancer. Subjects were treated with six cycles (21 day cycle) of pembrolizumab treatment combined with six consecutive weeks of concurrent BCG installation beginning with cycle 3 of pembrolizumab. The first three subjects were to be treated at a dose of 100 mg pembrolizumab to ensure safety for the combination. If no safety issues were to happen, dosing was to be escalated to 200 mg every three weeks. Our secondary objective was to determine the 19 week and the three, twelve, and twenty-four month post-treatment completion complete response rate. The first patient received cycle 1 of pembrolizumab treatment in July of 2015. As of the date of writing this letter, five patients have completed treatment on this trial. The trial is soon to open a second site at Henry Ford Health System in addition to Southern Illinois University with the goal of full enrollment to be achieved in the next 6 months

Acute scrotum in setting of acute pancreatitis.

Acute scrotum is a urologic emergency with many aetiologies. Acute scrotum in setting of acute pancreatitis is a rare occurrence and results from an effusion of pancreatic juices into the inguinal canal along a retroperitoneal tract. Knowledge regarding the existence of this obscure condition is essential for its diagnosis. It is thus important for medical professionals, particularly internists, surgical trainees and emergency physicians, to be aware of the condition and the options for its management

The Effect of Targeted Therapy for Genitourinary Malignancies on Sexual Function and Fertility.

PURPOSE OF REVIEW: Targeted therapy for genitourinary cancer is being used at an increasing rate. These medications show great survival benefit but are relatively lacking in long-term adverse effect data. With increasing survivability, measures to improve quality of life must be considered for GU cancer and a large proponent of this is sexual function. RECENT FINDINGS: mTOR inhibitors have shown an effect on testosterone levels and may have a link to abnormal semen parameters. Tyrosine kinase inhibitors (TKIs) have shown no adverse sexual outcomes in the literature. There are laboratory links to tyrosine kinases having a beneficial effect on erectile and sexual function. Possible sexual side effects must be discussed with patients receiving a diagnosis of cancer. Further research is required to determine the exact mechanisms and outcomes of sexual function with new and emerging targeted therapy

Ileus and small bowel obstruction after radical cystectomy for bladder cancer: Analysis from the Nationwide Inpatient Sample.

PURPOSE: To investigate prevalence and predictors of postoperative small bowel obstruction (SBO) and ileus in a large cohort of bladder cancer (BCa) patients treated with radical cystectomy (RC). METHODS: All patients within the Nationwide Inpatient Sample who underwent RC for BCa between 2006 and 2012 were identified. First, prevalence of SBO and ileus was analyzed. Second, predictors of these bowel-related complications were identified using multivariable regression analyses. Third, the association between SBO, ileus, and length of stay was evaluated using logistic regression models adjusted for clustering. Prolonged length of stay was defined as hospital stay above mean stay of the population (\u3e10 days). Fourth, the effect of SBO and ileus on mean inpatient cost of healthcare was examined. RESULTS: Of overall 41,498 patients, 1071 (2.6%) experienced SBO, and 11,155 (26.9%) experienced ileus. Predictors of ileus included age, male gender, black race, hospital characteristics, anemia, chronic pulmonary disease, drug abuse, hypothyroidism, fluid and electrolyte disorders, and neurological disorders (all p \u3c 0.05) Predictors of SBO included male gender, Asian/Pacific islander race, hospital characteristics, congestive heart failure, fluid and electrolyte disorders, and psychosis (all p \u3c 0.05). . Postoperative SBO (odds ratio (OR) 19.587; 95% confidence interval (CI):15.869-24.167) and ileus (OR 5.646; 95% CI:5.336-5.974) were associated with prolonged length of stay (all p \u3c 0.001).Median cost of hospital stay was $56.315 for patients who developed SBO,$32,472 for patients who developed ileus, and $24,600 for patients after cystectomy without ileus or SBO. CONCLUSIONS: Significant prevalence of bowel-related complications in patients after RC was observed. These complications are strongly associated with prolonged length of stay and higher healthcare cost. Increasing awareness of SBO and ileus, identification of patients at risk prior to surgery, and implementation of protective strategies are strongly indicated in cystectomy patients.