The goals of radiotherapy in this setting, just like surgery, are curative treatment with good local control and survival. The main benefit is to avoid surgical morbidity and mortality. It also preserved bladder function, sexual function, quality of like and patient body image.
The strength of her statement comes from a few recent institutional studies. This includes the work by the University of Toronto1 and MGH.2 Below, Kulkarni et al. demonstrate similar disease-specific survival (DSS) and overall survival (OS) for chemoradiation and NAC+RC in a propensity-matched cohort – acknowledging that they were quite selective with the patients they considered for chemoradiation.
A meta-analysis by Arcangeli et al. suggested a benefit to chemoradiation (TMT) over NAC+RC but does not include the more recent institutional results.3
Dr. Choudhury does acknowledge that she selects her patients for chemoradiation, specifically focusing on patients with localized MIBC, good bladder function, good performance status, and maximal TURBT. Those other institutions also suggest looking for patients without hydronephrosis (cT3+) and focusing on patients with isolated, focal tumor burden. Multifocal CIS is also a contraindication in some institutions.
Her next focus is on the role of radiosensitization. Most people agree that radiation alone is insufficient – radiosensitization with chemotherapy is an important part of all TMT regimens. The Level 1 evidence for this comes from 2 trials from the UK: BC2001 and BCON. In BC2001, 360 patients were randomized to either RT or CRT, and there was a 13% improvement in 2-year local-recurrence DFS with CRT. 5FU and mitomycin-C were the agents of choice for chemotherapy. In BCON, 333 patients were randomized to either RT or RT+chemotherapy, and there was a 13% improvement in OS at 3 years. In BCON, radiotherapy was combined with carbogen (oxygen) and nicotinamide. The results of both studies are seen below:
In terms of adverse events, Zeitman et al. have previously demonstrated that chemoradiation can be well tolerated.4 Efstathiou et al. demonstrated that Grade 3 GU and GI toxicity does not appear to exceed 5%5:
Dr. Choudhury then briefly spoke about the future of chemoradiation:
- MRI guided radiotherapy – with improved real-time MRI imaging, better targeting of the tumor and bladder may help reduce radiation to adjacent structures and increase the radiation dose to cancer.
- Predictive biomarkers – there is lots of work looking at various predictive biomarkers to select patients who are likely to benefit (or not benefit) from chemoradiation. This includes work by Dr. Choudary’s group as well.
- Molecular subtyping work of bladder cancer has also hinted at potential predictive ability of response to chemoradiation – Yang et al. seemed to suggest that patients with basal subtype have a significantly better response to chemoradiation, while luminal subtype does not affect response to chemoradiation.6
Written by: Thenappan Chandrasekar, MD, Clinical Instructor, Thomas Jefferson University, @tchandra_uromd, @JEFFUrology, at the 2019 ASCO Annual Meeting #ASCO19, May 31-June 4, 2019, Chicago, IL USA
- Kulkarni et al. Propensity Score Analysis of Radical Cystectomy Versus Bladder-Sparing Trimodal Therapy in the Setting of a Multidisciplinary Bladder Cancer Clinic. J Clin Oncol. 2017 Jul 10;35(20):2299-2305.
- Booth et al. Curative Therapy for Bladder Cancer in Routine Clinical Practice: A Population-based Outcomes study. Clinical Oncology, 2014 Aug;26(8):506-14.
- Arcangeli et al. Radical cystectomy versus organ-sparing trimodality treatment in muscle-invasive bladder cancer: A systematic review of clinical trials. Crit Rev Oncol Hematol. 2015 Sep;95(3):387-96.
- Zeitman et al. Organ conservation in invasive bladder cancer by transurethral resection, chemotherapy and radiation: results of a urodynamic and quality of life study on long-term survivors. J. Urol. 2003 Nov;170(5):1772-6.
- Efstathiou et al. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61.
- Yang et al. ASTRO 2017