Efstathiou on the Status of Bladder Preservation Therapy for Muscle-Invasive Bladder Cancer

Bladder preservation through tri-modality therapy with cystoscopic resection and chemoradiation represents a potential alternative to radical cystectomy for patients with muscle-invasive bladder cancer (MIBC). However, opportunities for improvement remain, according to Jason Efstathiou, MD, DPhil, who added that integration of immunotherapy may represent the next frontier of bladder preservation therapy.

“[Tri-modality therapy] can really help fill the gap in the undertreated population nationally and also serves as a good alternative to what has been the gold standard of radical cystectomy, [which] often comes with neoadjuvant chemotherapy, as well,” Efstathiou said in an interview with OncLive^®.

In the interview, Efstathiou discussed the current management of MIBC and ongoing research aimed at filling remaining gaps in the paradigm, including the SWOG/NRG 1806 trial (NCT03775265), which is assessing chemoradiation with or without atezolizumab (Tecentriq) in patients with localized MIBC.

Efstathiou is a professor of Radiation Oncology at Harvard Medical School, Vice-Chair of Faculty & Academic Affairs, and director of Genitourinary (GU) Service in the Department of Radiation Oncology, and clinical codirector of The Claire and John Bertucci Center for GU Cancers at Massachusetts General Hospital in Boston.

OncLive: Where does tri-modality therapy rank in the treatment of patients with MIBC?

Efstathiou: [I focused] on the state of the art of bladder preservation therapy forMIBC. The overall summary is that many patients with MIBC are not getting curative therapy nationally, they’re getting just a repeat TURBT, maybe some intravesical therapy, [which is] inadequate treatment for muscle-invasive disease, and that’s a pretty large proportion of patients. So, there’s an undertreated and underserved population with this serious disease. I discussed tri-modality therapy, which is a combination of cystoscopic resection of the bladder tumor and chemoradiation, [administered as] an attempt at bladder preservation.

The data have matured to support [that] this is a viable alternative for many patients with MIBC. The good news is that this treatment paradigm is supported by national guidelines; it has a category one recommendation per National Comprehensive Cancer Network guidelines, and it’s supported by numerous other guidelines as well. So, there’s that kind of support, too.

For patients that are getting bladder preservation therapy with tri-modality therapy, more than 85% of them are going to end up keeping their bladder and long-term quality of life is good for these patients. In clinically matched series, the best available data tells us that outcomes are as good as [those in] selected patients that are getting a radical cystectomy, so that’s reassuring. Not only is it a viable alternative but the outcomes could be just as good.

What areas of improvement exist in the treatment of patients with MIBC?

There are many opportunities to improve this treatment and to improve the management of MIBC in general. That includes improvement in the staging of the disease. During my talk I discussed the potential role of MRI and helping stage the disease upfront. Because this is a clinically under-staged disease, there’s a lot of clinical pathologic discordance, meaning if you take what the clinical stage was, and then the patients goes for radical cystectomy, for example, and you look at the pathologic stage, there can be quite a big discordance. So, we need to fix that clinical under-staging piece, and MRI is one tool that can help. In addition, there’s opportunities to improve radiation and how we deliver that.

There are opportunities towards hypofractionation, so shorter courses of radiation, the use of adaptive planning, where we adjust the treatment that is delivered that day to the patient to more optimally conform to their anatomy. There are opportunities to improve systemic treatment as well, and that means better concurrent therapies with radiation, perhaps the use of neoadjuvant therapies, perhaps even the use of novel therapies like immunotherapy with chemoradiation. On that point, it’s exciting that the largest ever fully accrued trial in bladder preservation therapy has just recently completed accrual. That’s the phase 3 SWOG NRG 1806 trial that is randomizing patients to chemoradiation [with or without atezolizumab]. We’re very excited that that trial is fully accrued and look forward to the results as they mature.

What does the future hold for this area?

Ultimately, the future also needs to have biomarker validation. A number of biomarkers have been looked at in the world of tri-modality therapy, but they need to be prospectively validated. [These biomarkers] may offer real guidance in the management of these patients and in treatment selection. It could be that there are certain biomarkers that indicate that a certain patient would benefit from chemoradiation, perhaps more so than surgery or vice versa, and that could enter the conversation when we counsel patients.