San Francisco, California (UroToday.com) Leslie Ballas, MD, Radiation Oncologist at University of Southern California, presented some of the most influential articles from the past year in the field of bladder cancer research from a radiation oncology perspective.
The first study that Dr. Ballas discussed referenced BC2001, a Phase 3 clinical trial that randomized 458 patients with cT2-4aN0M0 muscle-invasive bladder cancer (MIBC) to radiotherapy (RT) with or without chemotherapy. The median age in this cohort was 72. This study focused on health-related quality of life and patient-related outcomes of the trial.1 In both treatment arms, there was as significant decreased quality of life at the end of treatment, but this returned to baseline and was maintained in the five years of follow-up. Similar results were observed when comparing patients who received whole bladder versus reduced volume RT. Specific outcomes of urinary continence, urinary frequency, bowel control, and diarrhea all worsened at the end of treatment, but returned to baseline and were maintained through the five years of follow-up. Dr. Ballas concluded that that addition of concomitant chemotherapy (5-FU, Mitomycin-C) does not have a significant negative impact on health-related quality of life.
Transcriptional profiling of MIBC has identified molecular subtypes (luminal, basal) that may be predictive of outcomes to radical cystectomy with or without neoadjuvant chemotherapy. It’s unclear if molecular subtypes predict response to RT. In the study of interest, investigators performed whole transcriptome gene expression profiling to classify tri-modality therapy (TMT) patients using molecular subtypes and evaluated the association of immune and stromal gene signatures with clinically relevant endpoints.2The cohort included 136 patients who received TMT, 223 patients who received neoadjuvant chemotherapy and radical cystectomy, and the TCGA cohort of patients who underwent cystectomy without neoadjuvant chemotherapy. The main finding of this study is that there was no significant difference in pathologic complete response or overall survival (OS) in patients who underwent TMT. T-cell inflamed and higher IFN-gamma signature scores were associated with improved disease-specific survival after TMT. There was no association of stromal infiltration signature with outcomes in the TMT cohort, though high expression was associated with worse OS in patients who underwent cystectomy with or without neoadjuvant chemotherapy. 
There is an unmet need to define safety and efficacy of RT as a treatment modality for MIBC in elderly patients. Elderly patients who are unfit for surgery and cisplatin-based chemotherapy are seen in radiation oncology clinics. Only 11% of patients were older than 80 years old and only 3% had ECOG 2 in BC20001. Dr. Ballas highlighted two single-arm studies from the past year that evaluated RT in elderly patients with urothelial cancer (below), concluding that hypofractionated RT alone can provide local control in elderly patients unfit for chemotherapy.
The final paper discussed a Phase 1 trial of pembrolizumab with sequential versus concomitant stereotactic body radiotherapy (SBRT) in metastatic urothelial carcinoma. Pembrolizumab 200 mg was delivered every three weeks and three fractions of 800 cGy SBR was delivered to one metastatic lesion. The primary outcome was toxicity with secondary endpoints focused on efficacy.
6/9 patients on Arm A and 9/9 patients on Arm B had a grade 1-2 adverse event. There was only one grade 3 event (lymphopenia), which occurred on Arm B. No patients in Arm A had an objective response while 4 of 9 patients in Arm B had an objective response including 1 complete response. Progression-free survival was similar between the two arms, though overall survival was long on Arm B (12.1 months) than Arm A (4.5 months).
Presented by: Leslie K. Ballas, MD, Radiation Oncologist and Assistant Clinical Professor at University of Southern California
Written by: Jacob Berchuck, MD, Medical Oncology Fellow at the Dana-Farber Cancer Institute (Twitter: @jberchuck) at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California
References:
- Huddart RA, et al. Patient-reported Quality of Life Outcomes in Patients Treated for Muscle-invasive Bladder Cancer with Radiotherapy ± Chemotherapy in the BC2001 Phase III Randomised Controlled Trial. Eur Urol. 2020 Feb;77(2):260-268.
- Efstathiou JA, et al. Impact of Immune and Stromal Infiltration on Outcomes Following Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer. Eur Urol. 2019 Jul;76(1):59-68.
- Sundahl N, et al. Randomized Phase 1 Trial of Pembrolizumab with Sequential Versus Concomitant Stereotactic Body Radiotherapy in Metastatic Urothelial Carcinoma. Eur Urol. 2019 May;75(5):707-711.