As neoadjuvant enfortumab vedotin plus pembrolizumab (EVP) achieves high pathologic complete response rates in MIBC, a critical question emerges: is adjuvant EVP necessary for everyone? Continuing treatment in patients who are already cancer-free post-surgery may offer no extra benefit while increasing toxicity.

Achieving a pathologic complete response (path CR) in the bladder after neoadjuvant therapy is a marker of drug efficacy, not a signal to stop treatment. Because patients die from metastatic, not local, disease, a path CR should be seen as a reason to "double down" on the effective systemic therapy to eradicate micrometastases.

The NeoADURA trial demonstrates that adding osimertinib in the neoadjuvant setting for EGFR-mutated NSCLC results in a 'humongous benefit' in major pathological response and nodal downstaging compared to chemotherapy alone, significantly improving surgical outcomes.

With 72% response rates to neoadjuvant immunotherapy, surgeons are shifting from immediate, aggressive surgery to a "wait-and-see" approach. Shrinking the tumor first can turn a morbid, disfiguring operation into a much simpler procedure, fundamentally changing the initial surgical evaluation for cutaneous squamous cell carcinoma (CSCC).

In neoadjuvant therapy, a patient's long-term outcome is better predicted by stopping tumor DNA shedding (ctDNA clearance) than by achieving pathologic complete response (pCR), the traditional gold standard. This redefines what constitutes a successful treatment response before surgery.

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.

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.

In cisplatin-ineligible muscle-invasive bladder cancer, neoadjuvant enfortumab vedotin plus pembrolizumab demonstrated a 57% pathologic complete response rate in the KEYNOTE-905 trial. This is an unprecedented result, significantly higher than any previously studied regimen and signals a major shift in perioperative treatment.

In a neoadjuvant cemiplimab trial, only 6% of patients had a complete response based on radiographic imaging (RECIST criteria), yet 50% achieved a pathologic complete response. This major discrepancy shows clinicians should not rely solely on scans to assess treatment benefit before surgery.