Treatment of Low-grade Intermediate-risk Nonmuscle-invasive Bladder Cancer With UGN-102 ± Transurethral Resection of Bladder Tumor Compared to Transurethral Resection of Bladder Tumor Monotherapy: A Randomized, Controlled, Phase 3 Trial (ATLAS).

PURPOSE: Low-grade intermediate-risk nonmuscle-invasive bladder cancer is a chronic illness commonly treated by repetitive transurethral resection of bladder tumor. We compared the efficacy and safety of intravesical chemoablation with UGN-102 (a reverse thermal gel containing mitomycin), with or without subsequent transurethral resection of bladder tumor, to transurethral resection of bladder tumor alone in patients with low-grade intermediate-risk nonmuscle-invasive bladder cancer. MATERIALS AND METHODS: This prospective, randomized, phase 3 trial recruited patients with new or recurrent low-grade intermediate-risk nonmuscle-invasive bladder cancer to receive initial treatment with either UGN-102 once weekly for 6 weeks or transurethral resection of bladder tumor. Patients were followed quarterly by endoscopy, cytology, and for-cause biopsy. The primary end point was disease-free survival. All patients were followed for adverse events. RESULTS: Trial enrollment was halted by the sponsor to pursue an alternative development strategy after 282 of a planned 632 patients were randomized to UGN-102 ± subsequent transurethral resection of bladder tumor (n=142) or transurethral resection of bladder tumor monotherapy (n=140), rendering the trial underpowered to perform hypothesis testing. Patients were predominantly male and ≥65 years of age. Tumor-free complete response 3 months after initial treatment was achieved by 92 patients (65%) who received UGN-102 and 89 patients (64%) treated by transurethral resection of bladder tumor. The estimated probability of disease-free survival 15 months after randomization was 72% for UGN-102 ± transurethral resection of bladder tumor and 50% for transurethral resection of bladder tumor (hazard ratio 0.45). The most common adverse events (incidence ≥10%) in the UGN-102 group were dysuria, micturition urgency, nocturia, and pollakiuria. CONCLUSIONS: Primary, nonsurgical chemoablation with UGN-102 for the management of low-grade intermediate-risk nonmuscle-invasive bladder cancer offers a potential therapeutic alternative to immediate transurethral resection of bladder tumor monotherapy and warrants further investigation.

Surgical Anatomy and Dissection of the Hypogastric Plexus in Nerve-Sparing Radical Hysterectomy.

Radical hysterectomy is a central surgical procedure in gynecological oncology. A nerve-sparing approach is essential to minimize complications from iatrogenic injury to the pelvic nerves, resulting in postoperative urinary, anorectal, and sexual dysfunction. The hypogastric plexus (HP), a complex network of sympathetic and parasympathetic nerves, plays a critical role in pelvic autonomic innervation. This article offers a comprehensive overview of the surgical anatomy of the HP and provides a step-by-step description of HP dissection, with a particular emphasis on preserving the bladder nerve branches of the inferior HP. A thorough understanding and mastery of the anatomical and surgical nuances of HP dissection are crucial for optimizing outcomes in nerve-sparing gynecologic-oncological procedures.

A Randomized Phase II/III Study of Naptumomab Estafenatox + IFNα versus IFNα in Renal Cell Carcinoma: Final Analysis with Baseline Biomarker Subgroup and Trend Analysis.

PURPOSE: To prospectively determine the efficacy of naptumomab estafenatox (Nap) + IFNα versus IFN in metastatic renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: In a randomized, open-label, multicenter, phase II/III study, 513 patients with RCC received Nap (15 µg/kg i. v. in three cycles of four once-daily injections) + IFN (9 MU s.c. three times weekly), or the same regimen of IFN monotherapy. The primary endpoint was overall survival (OS). RESULTS: This phase II/III study did not meet its primary endpoint. Median OS/PFS for Nap + IFN patients was 17.1/5.8 months versus 17.5/5.8 months for the patients receiving IFN alone (P = 0.56; HR, 1.08/P = 0.41; HR, 0.92). Post hoc exploratory subgroup and trend analysis revealed that the baseline plasma concentrations of anti-SEA/E-120 (anti-Nap antibodies) for drug exposure and IL6 for immune status could be used as predictive biomarkers. A subgroup of patients (SG; n = 130) having concentrations below median of anti-SEA/E-120 and IL6 benefitted greatly from the addition of Nap. In SG, median OS/PFS for the patients treated with Nap + IFN was 63.3/13.7 months versus 31.1/5.8 months for the patients receiving IFN alone (P = 0.02; HR, 0.59/P = 0.02; HR, 0.62). Addition of Nap to IFN showed predicted and transient immune related AEs and the treatment had an acceptable safety profile. CONCLUSIONS: The study did not meet its primary endpoint. Nap + IFN has an acceptable safety profile, and results from post hoc subgroup analyses showed that the treatment might improve OS/PFS in a baseline biomarker-defined RCC patient subgroup. The results warrant further studies with Nap in this subgroup. Clin Cancer Res; 22(13); 3172-81. ©2016 AACR.