The role of neoadjuvant radiotherapy for locally-advanced rectal cancer with resectable synchronous metastasis

Although neoadjuvant radiotherapy is typically administered for locally-advanced rectal cancer to reduce local recurrence (LR), its role for patients who present with synchronous resectable liver and/or lung metastasis is not well defined. The aim of this study was to evaluate the role of neoadjuvant radiotherapy for patients with stage IV rectal cancer undergoing curative-intent surgery.

This study is a retrospective review of a prospectively maintained surgical registry of all consecutive adult patients who underwent curative-intent resection at Mayo Clinic in Rochester, MN, from January 1990 until December 2014 with a median follow-up time of 43 (IQR 16-67) months. Eligible patients had locally-advanced rectal cancer (T3, T4 and/or nodal involvement) with synchronous resectable liver and/or lung metastasis. Exclusion criteria were as follows: patients with primary tumor stage of T1N0 or T2N0, patients with metastasis to organs other than the liver or lung, patients who had palliative resection, patients who had non-surgical treatment of synchronous metastasis (e.g., radiofrequency ablation), patients who received postoperative radiotherapy, or absence of research authorization. Ninety three patients were included of which 47 received neoadjuvant radiotherapy and 46 did not. All patients received neoadjuvant chemotherapy +/- radiotherapy followed by curative-intent surgery with metastasectomy performed either simultaneously with resection of the primary tumor or as a planned staged resection. The primary outcomes of this study are LR, distant metastasis, overall and disease-specific survival (DSS).

LR was observed in 12 patients (26%) who did not receive radiotherapy, while no LR developed in those who received neoadjuvant radiotherapy, P<0.001. Univariate analysis showed that neither age, sex, ASA class, BMI, tumor location, procedure performed, or neoadjuvant chemotherapy were associated with subsequent LR. The 5-year overall survival (OS) rates were: 43.3% (95% CI: 30.1, 62.3) for no radiotherapy vs. 58.3% (95% CI: 43.4, 78.2) with radiotherapy.

Neoadjuvant radiotherapy should be considered in patients with locally-advanced stage IV rectal cancer. These data add to the evidence supporting neoadjuvant radiotherapy in the setting of resectable metastatic disease.