Implementing a Multimodal Prehabilitation Program to Radical Cystectomy in a Comprehensive Cancer Center: A Pilot Study to Assess Feasibility and Outcomes.

BACKGROUND: Radical cystectomy(RC) often leads to postoperative morbidity and complications. We conducted a pilot study on the effectiveness of multimodal prehabilitation, a preoperative conditioning method shown to be effective for colorectal surgery, in bladder cancer patients soon to undergo RC. We assessed patients' adherence to the prehabilitation regimen and changes in their physical condition. METHODS: Thirty-two bladder cancer patients at Memorial Sloan Kettering from February to August 2015 scheduled for RC were included in a standardized prehabilitation program. The 2-week program consisted of general physical exercises for the major muscle groups used for everyday activities, and sufficient protein intake. Patients received a program journal to document physical and nutritional achievements. Patients were physically tested using handgrip strength and bio-impedance at 2 weeks pre-surgery, day of surgery, and 6 weeks post-surgery. Additionally, a six-minute walk test (6MWT) 2 weeks before and 6 weeks after surgery were measured. RESULTS: Adherence to the exercises and nutritional recommendations respectively, was 62% (95% confidence interval [CI] 42-78%) for the exercise component and 81% (95% CI 62-93) for the nutritional component. The 6MWT results, showing physical capacity, significantly improved from baseline to 6-week follow-up, with an increase of 9.2% (95% CI 0.3-20.99; p=0.03). The handgrip strength, a proxy for nutritional status, improved 6.8% (95% CI 1.4-14.4; p=0.001) from baseline to admission, and maintained until 6-week follow-up (p=0.7). CONCLUSION: In a United States comprehensive cancer center, implementing a multimodal prehabilitation program is feasible in clinical practice and maintained. or even improved, physical functioning post-surgery compared to baseline.

Is restaging transurethral resection necessary in patients with non-muscle invasive bladder cancer and limited lamina propria invasion?

OBJECTIVES: To evaluate the influence of lamina propria invasion type at initial transurethral resection (TUR) on restaging pathology. MATERIALS AND METHODS: We reviewed prospectively maintained records of all patients with a high-grade pT1 nonmuscle invasive bladder cancer who underwent both initial and restaging TUR within 6 weeks at our center between 2001 and 2016. The pathology of second TUR specimens was analyzed with regard to the characteristics of lamina propria invasion found at initial resection. RESULTS: We included 198 patients, with a median age of 70 years (interquartile range: 63-79). Muscle was present in the initial TUR specimen in 107 patients (54%). Pathology restaging was pT0 in 73 patients (37%), pTis in 44 (22%), pTa in 27 (14%), pT1 in 50 (25%), and pT2 in 4 (2%). Eighty-seven patients (44%) had tumors with minimal lamina propria invasion at initial TUR: 53 specimens (27%) had focal invasion (few malignant cells in the lamina propria); 15 specimens (7.6%) had superficial invasion (invasion of the lamina propria to the level of the muscularis mucosae [T1a]); and 19 specimens (10%) had multifocal superficial invasion (multiple areas of T1a). Of the patients with minimal lamina propria invasion, residual disease was found in 54 patients (62%). However, none of those patients had T2 disease. CONCLUSIONS: A significant number of patients with T1 tumors have residual disease at restaging TUR as do patients with minimal lamina propria invasion. The extent of T1 invasion does not eliminate the need for repeat TUR.

Single Arm Phase I/II Study of Everolimus and Intravesical Gemcitabine in Patients with Primary or Secondary Carcinoma In Situ of the Bladder who failed Bacillus Calmette Guerin (NCT01259063).

Background: Standard treatment for BCG-refractory urothelial cancer is radical cystectomy. Identification of active agents is clearly warranted. Objective: To determine a safe dose of oral everolimus in combination with standard intravesical gemcitabine and to evaluate the efficacy of this combination. Methods: Patients with carcinoma in situ refractory to intravesical bacillus Calmette-Guérin and refusing cystectomy were eligible. Patients in the phase I part of the trial received one of three dose levels of oral everolimus. Patients also received a fixed dose of intravesical gemcitabine. Maintenance everolimus was given for 12 months in patients achieving a complete response confirmed by cystoscopy and cytology. Patients in phase II received continuous everolimus administered at 10 mg daily with intravesical gemcitabine followed by everolimus maintenance for 12 months of total therapy. The enrollment goal for the phase II was 33 patients. Results: 14 patients were enrolled in phase I of the trial. 23 patients were enrolled in phase II of the trial and 19 were evaluable for primary and secondary endpoints. Four patients withdrew consent prior to treatment initiation. Of the 19 patients evaluable for response, 3 (16%, 95% confidence interval [CI] 3% - 40%) were disease free at 1 yr. The probability of RFS was 20% (95% CI 5% - 42%) at 12 months. Ten patients out of 19 had grade 3 or greater toxicity events. Seven withdrew consent or were taken off study. Conclusions: Many patients withdrew, and enrollment was halted. Continuous oral everolimus plus intravesical gemcitabine was not well tolerated in this patient population where the threshold for tolerability is low.