Westerman, Mary E.

TPS909 Background: BCG-Exposed NMIBC (a high grade recurrence within 24 months of prior BCG, but not meeting “unresponsive” criteria) is a large patient population with a critical need for more effective treatment strategies that prevent the development of BCG unresponsive disease/progression. The current standard of care is re-treatment with BCG alone, but only ~50% of patients derive clinical benefit. While intravesical gemcitabine (with or without docetaxel) is sometimes used, multiple retrospective studies have found that GemDoce is no better than re-treatment with BCG alone for patients with BCG-exposed NMIBC. A chemoimmunotherapy strategy of intravesical Gemcitabine with BCG (GemBCG) combines the two most effective, inexpensive, and commonly used treatments for NMIBC. Based on compelling biologic rationale and preclinical data, a phase I/II (n=52) trial was initiated of GemBCG in BCG-exposed NMIBC (NCT04179162). GemBCG has minimal side effects (3.8% [2/52] with Grade 3 TRAEs (no grade 4/5 seen) with similar side effects and tolerability to BCG alone. GemBCG has a outstanding early efficacy signal (6-month complete response of 97% [28/29] in patients with CIS, compared to ~50% 6-month complete response w/ BCG alone for BCG exposed CIS). GemBCG has promising preliminary longer term efficacy (18-month HG-RFS of 76% compared to ~45-55% reported with BCG alone, GemDoce, and recombinant BCG in BCG exposed NMIBC). Correlative studies support the hypothesis that the addition of gemcitabine to BCG can favorably modulate the tumor immune microenvironment. Methods: Based on the above rationale, we initiated the “GAIN” trial (A032303/ NCT07000084), a prospective, multicenter, open-label phase III study for patients with BCG-exposed NMIBC randomized to either: re-treatment with BCG only (Arm A, SOC) or Gemcitabine + BCG (GemBCG, Arm B). BCG-exposed NMIBC is defined as a high grade NMIBC (Ta, T1, Tis/CIS) that has recurred within 24 months of prior BCG, but NOT otherwise currently meeting BCG unresponsive NMIBC. The primary objective is to compare high grade recurrence-free survival (HG-RFS) between the two treatment arms. Notable aspects of the trial include: (1) the reduced burden on investigators and research teams due to the NCI’s new streamlined data initiative, (2) liberal inclusion/exclusion criteria and pragmatic design to improve generalizability of results, and (3) Cystoscopic biopsies/TURBT at week 13/month 3 for all participants (both CIS and “papillary only”) for multiple reasons including to allow for earlier detection of BCG unresponsive disease for patient safety, increased rigor of the trial, and objectively evaluate urinary biomarkers/urinary tumor DNA. Clinical trial information: NCT04179162 .

PURPOSE To compare patient-reported and clinical outcomes between radical cystectomy (RC) and bladder-sparing therapy (BST) in patients with recurrent high-grade non–muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS This pragmatic, prospective observational cohort study was designed with patients, who selected and prioritized outcomes. Eligible adults were candidates for both RC or BST, had previous induction Bacillus Calmette-Guérin (BCG), and received their last treatment within 12 months. The primary outcome was the EORTC-QLQ-C30 physical function scale at 12 months. Secondary outcomes included other EORTC-QLQ-C30 scales, depression, anxiety, bladder cancer–specific quality of life (QOL), financial burden, and cancer-specific outcomes. Targeted maximum likelihood estimation (TMLE) was used to calculate average treatment effect (ATE) estimates between arms. Inverse probability weighted risk ratios (wRR) were calculated using quasi-Poisson regression. RESULTS Of 570 participants (mean age 71.4 years; 21% female), 371 selected BST and 199 selected RC. Physical function was significantly worse in the RC arm at 3 months; by 9 months, there was no difference between arms, and at 12 months, physical function did not differ (ATE, 0.9; 95% CI, –0.6 to 2.4; P = .22). RC was associated with better emotional function, generic health-related QOL, and financial burden, and lower depression and anxiety, while BST was associated with better bowel and sexual health. Cancer-specific survival was 99% for BST versus 96% for RC (wRR, 0.99; 95% CI, 0.97 to 1.01). RC was associated with a higher risk of adverse events and serious adverse events, including a 90-day mortality rate of 2.5%. CONCLUSION Most patient-prioritized outcomes were similar or better among participants who chose RC compared with BST. These findings support the continued role of RC in managing recurrent high-grade NMIBC.

Purpose The medical student performance evaluation (MSPE) summarizes a residency applicant’s academic performance. Despite attempts to improve standardized clerkship grading, concerns regarding grade inflation and variability at United States medical schools persist. This study’s aim was to describe current patterns of clerkship grading and applicant performance data provided in the MSPE. Method The authors evaluated Electronic Residency Application Service data submitted to a single institution for the 2016–2017 Match cycle. Clerkship grading characteristics regarding grading tiers, school rank, location, and size were obtained. Data regarding methods for summative comparisons such as key word utilization were also extracted. Descriptive statistics were generated, and generalized linear modeling was performed. Results Data were available for 137/140 (98%) MD-granting U.S. medical schools. Pass/fail grading was most commonly used during the preclinical years (47.4%). A 4-tier system was most common for clerkship grading (31%); however, 19 different grading schemes were identified. A median of 34% of students received the highest clerkship grade (range, 5%–97%). Students attending a top 20 medical school were more likely to receive the highest grade compared with those attending lower-rated schools (40% vs 32%, P < .001). Seventy-three percent of schools ranked students, most commonly using descriptive adjectives. Thirty-two different adjectives were used. Conclusions There is significant institutional variation in clinical grading practices and MSPE data. For core clerkships where most students received the highest grade, the ability to distinguish between applicants diminishes. A standardized approach to reporting clinical performance may allow for better comparison of residency applicants.

Abstract Background: We report the first case of instillation of alteplase, a tissue plasminogen activator, to dissolve occlusive upper urinary tract blood clot. Case Presentation: A 67-year-old Caucasian man with a solitary kidney became dialysis dependent because of upper urinary tract clot obstruction after ureteral stent placement for obstructing ureterolithiasis. After failure of more conservative measures, 10 mg of alteplase was instilled through nephrostomy tube daily for 2 consecutive days 30 minutes before manual irrigation with physiologic saline. After alteplase instillation, the occlusive blood clot dissolved with rapid improvement in urinary output and creatinine. Conclusions: Alteplase instillation through nephrostomy tube is a viable option to dissolve obstructing upper urinary tract blood clots.

Objectives To evaluate the prognostic significance of urinary collecting system invasion ( UCSI ) in a large series of patients with clear‐cell renal cell carcinoma ( RCC ). Materials and Methods Patients with clear‐cell RCC treated with nephrectomy between 2001 and 2010 were reviewed from a prospectively maintained registry. One urological pathologist re‐reviewed all slides. Cancer‐specific survival was estimated using the Kaplan–Meier method, and associations of UCSI with death from RCC were evaluated using Cox models. Results Of the 859 patients with clear‐cell RCC , 58 (6.8%) had UCSI . At last follow‐up, 310 patients had died from RCC at a median of 1.8 years after surgery. The median follow‐up for patients alive at last follow‐up was 8.2 years. The estimated cancer‐specific survival at 10 years after surgery for patients with UCSI was 17%, compared with 60% for patients without UCSI ( P < 0.001). In a multivariable model, UCSI remained independently associated with an increased risk of death from RCC (hazard ratio 1.5; P = 0.018). Further, among patients with pT 3 RCC , those with USCI had survival outcomes similar to those of patients with pT 4 RCC. Conclusions Collecting system invasion is associated with poor prognosis among patients with clear‐cell RCC . If validated, consideration should be given to including UCSI in future staging systems.

ABSTRACT Introduction High submuscular ectopic placement of inflatable penile prosthesis (IPP) reservoirs via the inguinal canal has been popularized as an alternative to the retropubic (orthotopic) location, particularly among men with prior pelvic surgery. Published results suggest minimal complications and high patient satisfaction. However, in our practice, we identified several patients presenting for IPP revision after high submuscular placement who were found to have reservoirs within the peritoneal cavity. Aim Given the potential for complications, we performed a cadaveric study to define the anatomic location of reservoirs placed using this technique. Methods We utilized 10 fresh male cadavers without embalming. Bilateral ectopic reservoir placement (10 AMS Conceal [Boston Scientific, Marlborough, MA] and 10 Coloplast Cloverleaf [Coloplast Corp, Humlebaek, Denmark]) was performed using the high submuscular technique via a penoscrotal incision. Strict adherence to published reports detailing the technique was emphasized to assure reliability of findings. Main Outcome Measures Anatomic dissection was performed to identify reservoir location within the abdominal wall layers. Results Twenty IPP reservoirs were placed without difficulty or concern for inadvertent malpositioning. Sixteen reservoirs (80%) were found anterior to the transversalis fascia, including 7 (35%) deep to the rectus muscle and 9 (45%) deep to the external oblique fascia and lateral to the rectus muscle belly. Two reservoirs (10%) were identified in the retroperitoneal space, while 1 (5%) was preperitoneal (deep to transversalis fascia) and 1 (5%) was intraperitoneal. Conclusion Placement of IPP reservoirs using the high submuscular technique results in variable anatomic locations, including within or immediately superficial to the peritoneal cavity. Given the lack of immediate recognition and risk of delayed complications with suboptimal reservoir placement, further studies are mandated to assess the long-term safety of the technique.