For bladder cancer patients with limited metastatic sites (oligometastatic disease) who respond well to systemic therapy, adding consolidative radiation like SBRT is a reasonable and well-tolerated strategy. This approach, supported by retrospective data and precedent in other cancers like prostate and kidney, aims to improve long-term disease control.
In real-world practice, oncologists are granting treatment breaks, or 'holidays,' to metastatic bladder cancer patients who achieve major responses on enfortumab vedotin-pembrolizumab. This practice, driven by toxicity management and quality of life concerns, is common despite the lack of formal trial data to guide the optimal duration or timing of discontinuation.
While severe (Grade 3+) neuropathy from enfortumab vedotin is rare, oncologists emphasize that Grade 2 toxicity is common and significantly impairs patients' quality of life. This 'moderate' side effect is often painful and interferes with daily activities, warranting an immediate hold on treatment, not just waiting for Grade 3.
For urothelial cancer patients treated with trastuzumab deruxtecan (TDXD), developing symptomatic (Grade 2) interstitial lung disease or pneumonitis is a critical event. Following protocols from other cancers, this requires permanent discontinuation of the therapy. Re-challenging the patient with TDXD after a Grade 2 event is not recommended without more disease-specific safety data.
When managing toxicities from trastuzumab deruxtecan (TDXD) in urothelial cancer, clinicians should refer to established protocols and literature from breast cancer, where experience is more extensive. This cross-disciplinary approach is necessary for managing side effects like nausea, vomiting, and lung disease until more bladder cancer-specific data becomes available.
The modern idea of performing surgery for bulky nodal disease after a strong response to EV-pembro has historical precedent. A 1999 study showed that 33% of patients who had a complete response to MVAC chemotherapy were alive at five years after surgery. This suggests more potent modern therapies could yield even better curative outcomes.