While neoadjuvant pembrolizumab (KEYNOTE-689) is now standard of care for resectable head and neck cancer, it carries a critical risk. During the pre-surgical treatment window, some patients may experience disease progression or toxicity that makes them ineligible for their planned curative surgery.

Despite strong data favoring pre-surgical systemic therapy, a surgeon argues that many patients will continue to undergo surgery first. This is due to real-world factors like surgeons being the point of diagnosis, urgent symptoms requiring rapid intervention, and patient preferences to have the tumor removed immediately.

A critical design flaw in most perioperative chemo-immunotherapy trials is the lack of a 'contribution of component' analysis. This makes it impossible to determine if the benefit comes from the neoadjuvant phase, the adjuvant phase, or both, thus complicating interpretation and clinical application.

The SANO trial's 'watch-and-wait' approach for esophageal cancer avoids initial surgical risks, showing superior survival for the first two years. However, the survival curves cross after that point, suggesting that surgery, despite its initial toll, may offer better long-term outcomes for patients who can tolerate the procedure.

The chemoradiation control arm in SUNRISE 2 performed so well (e.g., 95% 1-year overall survival) that it challenges the long-held belief that surgery is unequivocally superior. This result, alongside other recent studies, suggests chemoradiation should be considered a potent standard-of-care contender for bladder preservation in appropriately selected patients.

Some oncologists are stopping guideline-supported perioperative treatment regimens early if a patient achieves a pathologic complete response (pCR) from neoadjuvant therapy alone. This practice is considered premature and risky, as data from dedicated de-escalation trials like VOLGA is not yet available to support it.

While oncologists focus on the low 4% rate of Interstitial Lung Disease (ILD) from neoadjuvant TDXD, surgeons worry this complication could prevent patients from reaching potentially curative surgery, drawing parallels to issues seen with neoadjuvant immunotherapy.

For very early-stage small cell lung cancer, surgical resection is an important and perhaps underutilized option. Beyond its therapeutic potential, surgery provides a definitive pathological diagnosis, which is crucial as some cases that appear to be small cell on biopsy may actually be other tumor types, like atypical carcinoid.

While powerful drugs effectively shrink tumors, the response pattern can be a "splatter" rather than a uniform deflation. This creates a significant surgical challenge, making it difficult to define clear margins for breast-conserving surgery and potentially necessitating a more extensive operation despite a good therapeutic response.