The first highlighted study concerns the use of intravesical nadofaragene firadenovec gene therapy for the treatment of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) published by Boorjian et al. This was a Phase III, single-arm, multi-center study of this recombinant adenovirus delivering alfa-2b cDNA into the bladder epithelium. Overall, 157 patients were enrolled into two cohorts based on whether carcinoma in situ (CIS) was present. At 3 months, the CIS cohort (comprising 103 patients) had a complete response rate of 53% with a duration of complete response of 9.7 months. Patients without CIS had a somewhat higher complete response rate (73%) and a longer duration of response (12.4 months).
As expected, response rates declined over time though, overall, 31% of patients were free from high-grade recurrence at 12 months. Over a 30-month follow-up, patients without CIS have somewhat higher rates of high-grade recurrence-free survival. Dr. Herrel concluded that Adstiladrin® is efficacious with a convenient dosing schedule and acceptable safety.
The second study that Dr. Herrel highlighted is a multi-institutional assessment of sequential intravesical gemcitabine and docetaxel and docetaxel for NMIBC.
Following this induction regime, patients were offered once monthly maintenance dosing if they remained recurrence-free.
The authors included 276 patients who had a median of 1 prior course of BCG and 38% of whom met the definition for BCG-unresponsive disease. These patients were followed for a median of 23 months following treatment. Notably, 9 patients were unable to tolerate the full course. However, of those who did, bladder recurrence-free survival was 60% at 1 year and 46% at 2 years. High-grade recurrence-free survival was somewhat higher at 65% and 52% at 1 and 2 years, respectively. Notably, among patients with BCG unresponsive disease, 2-year high-grade recurrence-free survival in patients with any CIS and those with high-grade papillary lesions without CIS was 50% and 58%, respectively. From these data, Dr. Herrel concluded that gemcitabine/docetaxel is effective as rescue therapy following BCG for NMIBC with low rates of progression at 2 years. Notably, monthly maintenance was favourable associated with a lack of recurrence.
The third study that Dr. Herrel highlighted is a report from the RAZOR trial examining health-related quality of life. Among patients in the RAZOR trial randomized between open and robotic radical cystectomy, the authors assessed health-related quality of life at baseline at 3 months and 6 months using the FACT-Vanderbilt Cystectomy Index and the SFHS-8. In their analysis, the authors considered continent and incontinent urinary diversions.
As highlighted in the figures, health-related quality of life did not meaningfully differ for patients who were treated with open or robotic radical cystectomy across any domain.
Notably, emotional well being improved at 3 and 6 months compared to baseline, regardless of treatment approach. Interestingly, higher BMI and postoperative complications were associated with worse health-related quality of life. Similarly, both physical and mental well being improved from baseline at 3 and 6 months for patients in the open arm.
In their exploratory analysis assessing diversion type, there were no differences in most domains, except for higher scores in the FACT-BL-Cys at 3 months among patients with incontinent diversion and greater improvements compared to baseline at 6 months with respect to PCS among those with continent diversions. However, Dr. Herrel noted that unlike the open and robotic comparison, these exploratory analyses were conducted amongst non-randomized data.
In summarizing these data, Dr. Herrel noted that health-related quality of life is not impacted by the surgical approach and there are no clear differences on the basis of diversion type.
Finally, Dr. Herrel discussed the safety of radical cystectomy following neoadjuvant pembrolizumab based on the PURE-01 trial. This study specifically looked at 68 patients who received neoadjuvant pembrolizumab. In this report, 90-day perioperative outcomes were compared to patients treated with neoadjuvant chemotherapy (MVAC). In general, 90-day perioperative outcomes were comparable between the two groups. However, patients who received pembrolizumab had a somewhat longer length of stay and lower rates of blood transfusion. However, other rates of complications were generally comparable both to patients receiving neoadjuvant chemotherapy in this comparison and to the literature. Thus, Dr. Herrel concludes that surgery after neoadjuvant immunotherapy is feasible without significant differences from patients who received neoadjuvant chemotherapy.
Presented by: Lindsey A. Herrel, MD, Assistant Professor, Department of Urology, University of Michigan, Ann Arbor, Michigan
Written by: Christopher J.D. Wallis, MD, PhD, Urologic Oncology Fellow, Vanderbilt University Medical Center, Nashville, Tennessee, Twitter: @WallisCJD during the 2021 ASCO Genitourinary Cancers Symposium (ASCO GU), February 11th to 13th, 2021