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Exploring Alternative Treatment Options for Muscle-Invasive Bladder Cancer
The conventional approach for localized muscle-invasive bladder cancer (MIBC) is radical cystectomy, which involves the complete removal of the bladder. While this surgical intervention is often successful in treating the disease, it can have profound effects on a patient’s quality of life, as noted by medical expert Garcia-del-Muro.
Garcia-del-Muro emphasizes that “Radical cystectomy is a highly invasive procedure that can substantially alter a patient’s life.” The surgery can lead to issues such as self-consciousness due to urostomy bags, as well as discomfort from neobladder reconstructions. This has prompted interest in multimodal treatments, which may provide less invasive options worthy of further investigation.
One non-invasive strategy currently being studied involves a combination of transurethral tumor resection, followed by chemotherapy and radiotherapy. Despite showing some promise, the use of chemotherapy comes with notable toxicity, making up to half of the patients ineligible for this treatment while reinforcing the search for alternative therapies, according to Garcia-del-Muro.
On the other hand, preclinical research indicates that immune checkpoint inhibitors (ICIs) like durvalumab, which targets PD-L1, and tremelimumab, which focuses on CTLA-4, may work well in conjunction with radiotherapy. This combination appears to result in fewer side effects compared to traditional chemotherapy. Additionally, radiation can stimulate cancer cells to release immune-activating signals, enhancing the effectiveness of ICIs. Garcia-del-Muro elaborated on this potential synergy, which supports ongoing research efforts.
To further investigate these avenues, Garcia-del-Muro and colleagues initiated the IMMUNOPRESERVE trial, a phase II, multicenter, single-arm, open-label study aimed at assessing the effects of combining radiation with durvalumab and tremelimumab to preserve the bladders of patients with localized MIBC. The study involved 32 patients diagnosed with stage T2-T4a disease, who had not previously received immunotherapy (excluding Bacillus Calmette-Guérin [BCG]) or radiation to the bladder. These patients were either deemed ineligible for or opted out of cystectomy. Participants completed three cycles of durvalumab and tremelimumab, each spaced four weeks apart, while undergoing concurrent radiotherapy.
Of the 28 patients who were evaluated, an impressive 26 individuals (93%) achieved a complete response. Across the overall study group, after a two-year follow-up, five patients (16%) exhibited metastatic recurrences, six (19%) showed recurrences of muscle-invasive disease, and one (3%) had a recurrence of non-muscle invasive disease.
After a median follow-up period of 27 months, the results were promising, with 30 of the patients successfully preserving their bladders, while only two patients required radical cystectomy due to disease recurrence.
The preliminary data suggests that the two-year overall survival rate and the rate of distant metastasis-free survival were estimated at 84% and 83%, respectively. When considering safety, Garcia-del-Muro reported that the treatment regimen was well tolerated overall, though 31% of participants experienced severe grade 3 or 4 adverse events, and there was one instance of a treatment-related death. Additionally, eight patients (25%) did not complete the planned third immunotherapy dose due to associated toxicity.
“This multimodal approach to preserving the bladder is feasible and demonstrates high efficacy in response and long-term bladder retention,” remarked Garcia-del-Muro, who expressed hopes for larger studies that would not only involve more participants but also compare the treatment directly with other standard options that combine radiation and chemotherapy.
Although this exploratory study yields optimistic results, Garcia-del-Muro points out some limitations, including the small sample size, relatively brief follow-up duration, and the absence of comparisons to established treatment protocols. “The outcomes are encouraging and highlight the potential for radiotherapy coupled with combination immunotherapy to enhance patient quality of life while maintaining survival rates,” he concluded.
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