San Francisco, CA (UroToday.com) Dr. Leslie Ballas gave an overview of the top publications in urothelial carcinoma from the perspective of a radiation oncologist. The papers discussed included those dealing with radiotherapy in the definitive management of muscle-invasive bladder cancer and radiotherapy in the management of oligometastatic muscle-invasive bladder cancer.
The first paper was on patient-reported quality of life outcomes in patients treated for muscle-invasive bladder cancer with radiotherapy and chemotherapy.1 The authors used a health-related quality of life questionnaire (FACT-BL) and gave it to patients at baseline, end of treatment and following treatment annually for a duration of 5 years. The results are shown in Figure 1. Other comparisons between chemotherapy-treated patients and whole bladder versus reduced volume treated patients are shown in figure 2.
Figure 1. Mean change from baseline
Figure 2. Health-related quality of life outcomes in the overall trial population
Dr. Ballas summarised this study and stated that this is the largest study of prospectively collected patient-reported outcomes after tri-modal therapy for muscle-invasive bladder cancer, within a randomized control trial. The trial showed that after an initial decline in health-related quality of life immediately following radiotherapy, the health-related quality of life returns to baseline and is maintained at 5 years. Additionally, emotional well being improved at the end of treatment and beyond. Lastly, the addition of concomitant chemotherapy does not have a significant impact on the health-related quality of life.
The second study discussed was a study assessing the impact of immune and stromal infiltration on outcomes following bladder sparing tri-modal therapy for muscle-invasive bladder cancer.2 Transcriptional profiling of muscle-invasive bladder cancer has identified molecular subtypes that may be predictive of outcomes to radical cystectomy. The authors of this study also performed whole transcriptome gene expression profiling to classify tri-modal therapy patients using molecular subtypes and evaluating the association of immune and stromal gene signatures with clinically relevant endpoints. The study included overall 136 patients treated with tri-modal therapy, 226 patients treated with neoadjuvant chemotherapy and radical cystectomy, and a TCGA cohort of radical cystectomy treated patients without neoadjuvant chemotherapy.
The results showed that the rate of complete response following tri-modal therapy was not different across the various subtypes. No effect of molecular subtype on either disease-specific survival or overall survival was seen in the tri-modal therapy cohort. Interestingly, immune infiltration was associated with an improved response to tri-modal therapy (Table 1). Stromal signature scores varied across subtypes with scores highest in the luminal infiltrated subgroup and lowest in the luminal subgroup (Table 2).
Table 1. Immune infiltration associated with trimodal therapy
Table 2. Stromal infiltration association with outcomes
Dr. Ballas Concluded that the tumor microenvironment is associated with clinical outcomes based on different treatments for muscle-invasive bladder cancer. However, immune infiltration in muscle-invasive bladder cancer is associated with improved disease-specific survival after tri-modal therapy. Higher stromal infiltration is associated with the shortest disease-specific survival after neoadjuvant chemotherapy and radical cystectomy. Lastly, clinical outcomes across molecular subtypes do not vary within the trimodal therapy cohort.
The last manuscript mentioned is a randomized Phase I trial assessing pembrolizumab with sequential versus concomitant stereotactic body radiotherapy in metastatic urothelial carcinoma.3 The trial design is shown in figure 3. The primary outcome was toxicity and the secondary endpoints included objective response rate using the RECIST criteria, progression-free survival, overall survival, and local response at irradiated lesion as per RECIST criteria.
Figure 3. Trial design
All patients with a complete response at the SBRT lesion experienced a decline in CTDNA fraction after SBRT. Dr. Ballas concluded that pembrolizumab can be safely combined with SBRT both sequentially and concomitantly. The overall response rate of 44% in the concomitant arm seemed promising. The monitoring of ctDNA fraction during treatment could be useful in predicting treatment response in metastatic urothelial carcinoma.
Presented by: Leslie K. Ballas, MD, Associate Professor of Clinical Radiation Oncology, University of Southern California
Written by: Hanan Goldberg, MD, Urology Department, SUNY Upstate Medical University, Syracuse, New York, Twitter: @GoldbergHanan at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California
References:
- Huddart RA, Hall E, Lewis R, 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; 77(2): 260-8.
- Efstathiou JA, Mouw KW, Gibb EA, et al. Impact of Immune and Stromal Infiltration on Outcomes Following Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer. Eur Urol 2019; 76(1): 59-68.
- Sundahl N, Vandekerkhove G, Decaestecker K, et al. Randomized Phase 1 Trial of Pembrolizumab with Sequential Versus Concomitant Stereotactic Body Radiotherapy in Metastatic Urothelial Carcinoma. Eur Urol 2019; 75(5): 707-11.