SELECTIVE VERSUS ROUTINE SURGICAL RESECTION FOR RECTAL CANCER FOLLOWING NEOADJUVANT CHEMORADIATION AND CLINICAL COMPLETE RESPONSE

Purpose: Approximately 25% of rectal cancer patients with a clinical complete response (CR) after neoadjuvant chemoradiation will ultimately be found to have a “true” pathologic CR at both the primary tumor site and the mesorectum at the time of surgical resection (SR; which requires partial/total removal of the rectum). Minimally invasive, transanal local excision (LE) of the primary tumor site after chemoradiation may identify patients who achieved a true pathologic CR after neoadjuvant therapy, and thus, may not require (and/or benefit from) SR. The purpose of this study was to explore the predictive/therapeutic value of selective SR (i.e., based on results of LE) versus routine SR in this patient population.

Method(s): We developed a decision analysis/Markov model to compare outcomes following selective versus SR in patients with mid-low rectal cancers with a clinical CR after chemoradiation. All patients in the selective SR strategy underwent LE after chemoradiation: patients with a pathologic CR at the primary tumor site were observed, while those with residual disease at the primary tumor site underwent subsequent SR. All patients in the routine SR strategy underwent upfront resection after chemoradiation. Sensitivity/specificity of LE, morbidity/mortality of LE/SR, local/systemic recurrence estimates after LE/SR, rates of surgical salvage after local recurrence following LE/SR, and survival estimates were obtained from the medical literature. Model outcomes were quality-adjusted using health state preferences.

Result(s): Overall, unadjusted and quality-adjusted life expectancy was superior after selective SR compared to routine SR; patients with a true pathologic CR gained the greatest benefit (Table 1).  Selective SR was the optimal strategy even after model estimates/utilities were varied widely over their reported ranges. Routine SR was preferred only if model estimates/utilities were varied well beyond their reported ranges: if mortality of LE, probability of a true pathologic CR, and utility of being disease-free after LE (without subsequent SR) were assumed to be >4.5%, <0.2%, and 0.846, respectively.

Conclusion(s): Selective SR (based on results of LE) maximizes unadjusted and quality-adjusted life expectancy compared to upfront routine SR in patients with mid-low rectal cancers with a clinical CR after neoadjuvant chemoradiation. Routine SR in this increasingly common clinical situation should be reconsidered. Randomized trials comparing selective versus routine SR (that prospectively measure resulting health-state preferences and costs) in this setting are warranted.