In patients achieving a complete response on EV-pembrolizumab, leading oncologists are using circulating tumor DNA (ctDNA) clearance in clinical practice to increase confidence and facilitate shared decision-making around stopping treatment, despite it not being standard of care.

In advanced gastroesophageal cancer, a common clinical practice for patients achieving a complete response on immunotherapy is to stop treatment after two years. For those with residual disease confirmed by biopsy, clinicians advocate for extending therapy beyond this point, contingent on payer approval.

While median survival improvements in advanced HCC are notable, the truly revolutionary impact of immunotherapy is the creation of a long-term survival "tail" on the Kaplan-Meier curve. Clinicians now manage patients for years, a reality that was nonexistent in the pre-IO era.

Traditional endpoints like progression-free survival (PFS) incentivize continuous treatment. The NCI group proposes "treatment-free survival," a novel metric that quantifies time spent *off* therapy. This endpoint better captures the patient experience and rewards treatments that provide durable responses after a finite course.

Dr. Carbone argues that traditional metrics like median survival or response rate are less relevant for immunotherapies. The true measure of success is the percentage of patients alive at five or six years—the "tail of the curve"—as this indicates a durable, potentially curative, response.

The next frontier in CSCC isn't just about new drugs, but about optimizing existing ones. A key research area is determining the minimum number of immunotherapy doses required for an optimal response—potentially just one or two—to limit toxicity, reduce treatment burden, and personalize care for high-risk patients.

Data from trials like CheckMate 816 shows that achieving a Pathologic Complete Response (PCR) after neoadjuvant chemo-immunotherapy is a powerful early surrogate endpoint. Patients with PCR demonstrate markedly improved overall and event-free survival.

While continuous therapy remains the official standard of care for mHSPC, there's a growing consensus for individualized de-intensification. For patients with a sustained, undetectable PSA (e.g., for two years), clinicians are increasingly comfortable discussing stopping all treatments to improve quality of life and reduce toxicity.

Patients showing a near-complete response at the end of a six-month immunotherapy course may still convert to a full complete response two months later without additional treatment. Clinicians should consider 'holding their nerve' and re-evaluating with repeat imaging before altering the treatment plan.