An advisory panel split 50/50 on a two-year immunotherapy regimen but voted 7-to-1 for a one-year drug with similar efficacy. This reveals that for adjuvant therapies in non-metastatic cancer, halving the treatment duration and toxicity exposure can decisively shift the risk/benefit calculation in favor of approval.

Even in healthcare systems with universal free access, like the UK's NHS, the actual uptake of immunotherapy for metastatic kidney cancer is only about 60%. This real-world gap strengthens the argument for adjuvant therapy, as it ensures high-risk patients receive potentially life-saving treatment they might otherwise miss upon relapse.

Historically, discussing adjuvant therapy for Stage III colon cancer was quick and straightforward, while Stage II was complex. The advent of ctDNA testing has reversed this dynamic. Stage II decisions are now clearer (treat if positive), while Stage III discussions have become much longer and more nuanced as clinicians integrate ctDNA data with patient preferences.

When debating immunotherapy risks, clinicians separate manageable side effects from truly life-altering events. Hypothyroidism requiring a daily pill is deemed acceptable, whereas toxicities like diabetes or myocarditis (each ~1% risk) are viewed as major concerns that heavily weigh on the risk-benefit scale for early-stage disease.

The practice-changing DYNAMIC trial showed that a ctDNA-guided strategy for stage II colorectal cancer reduces adjuvant chemotherapy use by 50%. Despite this significant de-escalation of treatment, patient outcomes and survival rates were identical to the standard-of-care approach.

The PR21 trial showed better overall survival for docetaxel followed by Lutetium, despite similar progression-free survival. The likely reason is not drug superiority but patient behavior: a higher percentage of patients complete the second therapy when starting with chemo, highlighting how treatment fatigue significantly impacts survival.

In the AMPLITUDE trial, only 16% of high-risk metastatic prostate cancer patients received docetaxel, despite it being allowed and indicated by disease characteristics. This suggests a real-world "chemophobia" or physician bias towards newer targeted therapies, even within a clinical trial setting.

Modern breast cancer treatment has shifted from a 'one-size-fits-all' aggressive approach to a highly individualized one. By de-escalating care—doing smaller surgeries, minimizing radiation, and sometimes omitting chemotherapy or lymph node biopsies—clinicians can achieve better outcomes with fewer long-term complications for patients with favorable disease characteristics.

Observational data from the BESPOKE study showed that the survival benefit from adjuvant chemotherapy was only seen in patients who tested positive for ctDNA post-surgery. In contrast, ctDNA-negative patients had overlapping survival curves whether they received chemotherapy or not, questioning its utility for that group.