Pathologic response to preoperative therapy: does it mean what we think it means?

Area of Science:

• Oncology
• Pathology
• Clinical Trial Design

Background:

• Preoperative chemotherapy and radiation often lead to observable tumor response in surgical specimens.
• Pathologic response is frequently used as a surrogate for patient recurrence and survival outcomes.
• Validating surrogates can streamline the investigation of novel treatment strategies.

Purpose of the Study:

• To review the current evidence supporting pathologic response as a reliable surrogate for tumor behavior.
• To discuss definitions of pathologic response and its implications across common tumor types.
• To explore factors causing discordance between observed tumor response and actual patient outcomes.

Main Methods:

• Systematic literature review of studies evaluating pathologic response as a surrogate endpoint.
• Analysis of definitions and interpretations of pathologic response in various cancers.
• Examination of confounding factors affecting the correlation between pathologic response and clinical outcomes.

Main Results:

• Pathologic response shows potential as a surrogate endpoint, but its predictive value varies by tumor type.
• Inconsistent definitions and confounding factors can lead to discordance between response and outcomes.
• Alternative methods for assessing treatment response are also considered.

Conclusions:

• Pathologic response is a promising surrogate endpoint for preoperative cancer therapy trials, potentially reducing trial duration and cost.
• Further standardization of definitions and careful consideration of confounding factors are necessary for its reliable application.
• Exploring alternative response assessment strategies may complement pathologic evaluation.