Standard RECIST criteria can misclassify a significant response as "stable disease." A desmoid tumor can shrink dramatically in volume (from a "softball" to a "pencil") but maintain its length, showing no change by RECIST. This suggests clinicians are likely underestimating the true benefit of therapies.

A major diagnostic challenge in bladder-sparing therapy for T4 tumors is the "fibrotic scar." When a large tumor responds to therapy, it leaves behind fibrotic tissue that is indistinguishable from residual cancer on an MRI, making it nearly impossible to confirm a true complete response.

The traditional six-month timeframe for defining platinum sensitivity is being challenged. A growing theory suggests that tumors progressing while on a PARP inhibitor have a distinct biology that responds poorly to subsequent platinum, indicating a potential need to move directly to therapies like ADCs.

Hormone receptor-positive (HR+) HER2+ breast cancers often show lower rates of pathologic complete response (pCR) to pre-surgical therapy. This is due to their slower-growing biology, not treatment ineffectiveness. Clinicians should recognize this nuance and not assume a worse prognosis based on pCR alone in this subtype.

Real-world data shows that in platinum-sensitive ovarian cancer patients who have progressed on PARP inhibitors, subsequent platinum-based chemotherapy has a surprisingly low response rate of only 20%. This quantifies a significant opportunity for highly active ADCs to potentially replace platinum in this growing patient population.

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.

For HRD-positive ovarian cancer, a strong initial response to platinum chemotherapy may justify using a PARP inhibitor alone for maintenance. A weaker response, however, suggests adding bevacizumab for a potentially greater benefit, using clinical response as a key decision-making tool.

The interpretation of ctDNA is context-dependent. Unlike in the adjuvant setting, in the neoadjuvant setting, remaining ctDNA positive post-treatment signifies that the current therapy has failed. These high-risk patients need a different therapeutic approach, not an extension of the ineffective one.

The initial broad enthusiasm for PARP inhibitors in ovarian cancer has been refined. New data confirms a lack of overall survival improvement for patients with HRD-negative (or HR proficient) tumors, pushing clinicians toward a precision medicine approach where these drugs are reserved for patients with BRCA mutations or HRD-positive disease who are most likely to benefit.