Can Response-Adapted Therapy Help Patients Avoid Bladder Cancer Surgery?

The evolving treatment landscape in muscle-invasive bladder cancer (MIBC) is creating opportunities to explore response-adapted strategies that could reduce treatment intensity for patients who achieve deep responses or complete responses (CRs), according to Andrea Necchi, MD, professor of medical oncology at Vita-Salute San Raffaele University in Milan, Italy, and director of genitourinary medical oncology at San Raffaele Hospital.

In an interview with Targeted Onc, Necchi discusses how future MIBC trials could build on recent findings to investigate treatment de-escalation, including approaches that may allow some patients to avoid additional adjuvant therapy or radical cystectomy. He emphasizes that reducing the surgical component of treatment could have a particularly meaningful effect on patients’ quality of life.

Necchi points to findings from the phase 3 VOLGA trial (NCT04960709), presented at the 2026 European Society for Medical Oncology Congress, as evidence that certain components of adjuvant treatment may be candidates for de-escalation. Specifically, the findings suggested that removing the enfortumab vedotin (EV; Padcev) combination from the adjuvant treatment approach may be feasible. He contrasts this with the potential impact of avoiding surgery, which he describes as an even more substantial opportunity to reduce treatment-related burden.

Looking ahead, Necchi identifies intensified, shorter-course neoadjuvant induction therapy as one potential direction for clinical research. In this approach, investigators could evaluate whether patients who achieve a deep response or CR after initial treatment can safely discontinue subsequent components of the treatment paradigm.

One strategy would be to improve CR rates beyond the approximately 60% benchmark associated with ipilimumab (Yervoy) plus pembrolizumab (Keytruda). Necchi suggests that adding a third agent could be worthwhile if it increases CR rates to approximately 80% without introducing additional adverse effects. Such findings could support further investigation of whether selected patients can achieve favorable outcomes while avoiding subsequent treatment, including surgery and adjuvant therapy.

This approach could offer several potential advantages, including reduced treatment-related toxicity, preservation of quality of life, and lower health care costs. Shortening treatment could also reduce demands on hospitals and infusion facilities.

Ultimately, Necchi emphasizes that future MIBC research should focus not only on improving response rates but also on identifying patients who may benefit from less intensive treatment. Response-adapted strategies could help move the field toward more individualized treatment approaches while potentially sparing patients from the lasting effects of surgery and additional systemic therapy.