Following high response rates to systemic therapies like EV Pembro, using radiation for bladder preservation is now questioned. It may constitute overtreatment by radiating a now cancer-free organ, while providing no benefit for the systemic micrometastases that are the primary driver of mortality.

An expert argues the path to curing metastatic cancer may mirror pediatric ALL's history: combining all highly active drugs upfront. Instead of sequencing treatments after failure, the focus should be on powerful initial regimens that eradicate cancer, even if it means higher initial toxicity.

Developers often test novel agents in late-line settings because the control arm is weaker, increasing the statistical chance of success. However, this strategy may doom effective immunotherapies by testing them in biologically hostile, resistant tumors, masking their true potential.

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.

Before the LAURA trial, oncologists had strong data for using EGFR TKIs in metastatic and resectable settings but lacked evidence for the unresectable Stage 3 population receiving chemoradiation. LAURA filled this "awkward gap," confirming a long-held suspicion and harmonizing treatment strategy across disease stages.

An overall survival (OS) benefit in an adjuvant trial may not be meaningful for patients in systems (e.g., the U.S.) with guaranteed access to the same effective immunotherapy upon recurrence. The crucial, unanswered question is whether treating micrometastatic disease is inherently superior to treating macroscopic disease later, a distinction current trial data doesn't clarify.

The success of perioperative osimertinib means oncologists cannot choose the optimal strategy (targeted therapy vs. chemoimmunotherapy) for resectable lung cancer without first knowing the patient's EGFR, ALK, and PD-L1 status. This elevates biomarker profiling from a metastatic-setting tool to a critical first step in early-stage disease.

A significant criticism of the pivotal KEYNOTE-564 trial is that only half the patients in the control arm received standard-of-care immunotherapy upon relapse. This lack of subsequent optimal treatment complicates the interpretation of the overall survival benefit, raising questions about its true magnitude.

Unlike immunotherapy, neoadjuvant osimertinib yields poor pathologic complete response (pCR) rates. However, it significantly improves major pathologic response (MPR) and survival, suggesting pCR may be the wrong efficacy endpoint for cytostatic EGFR TKIs, which have a different mechanism of action than immunotherapy.