Patterns of failure in patients with locally advanced rectal cancer receiving pre-operative or post-operative chemoradiotherapy

BACKGROUND: We investigated patterns of failure in patients with locally advanced rectal cancer (LARC) according to chemoradiotherapy (CRT) timing: pre-operative versus post-operative. Also, patterns of failure, particularly distant metastasis (DM), were analyzed according to tumor location within the rectum. METHODS: In total, 872 patients with LARC who had undergone concurrent CRT and radical surgery between 2001 and 2007 were analyzed retrospectively. Concurrent CRT was administered pre-operatively (cT3–4) or post-operatively (pT3–4 or pN+) in 550 (63.1%) and 322 (36.9%) patients, respectively. Median follow-up period was 86 (range, 12–133) months for 673 living patients. Local recurrence (LR) was defined as any disease recurrence within the pelvis, and any failure outside the pelvis was classified as a DM. Only the first site of recurrence was scored. RESULTS: In total, 226 (25.9%) patients developed disease recurrence. In the pre-operative CRT group, the incidences of isolated LR, combined LR and DM, and isolated DM were 17, 21, and 89 patients, respectively. In the post-operative CRT group, these incidences were 8, 15, and 76 patients, respectively. LR within 2 years constituted 44.7% and 60.9% of all LRs in the pre-operative and post-operative CRT groups, respectively. Late (> 5 years) LR comprised 13.2% and 4.3% of all LRs in the pre-operative and post-operative CRT groups, respectively. The lung was the most common DM site (108/249, 43.4%). Lung or para-aortic lymph node metastasis developed more commonly from low-to-mid rectal tumors while liver metastasis developed more commonly from upper rectal tumors. Lung metastasis occurred later than liver metastasis (n = 54; 22.6 ± 15.6 vs. 17.4 ± 12.1 months; P = 0.035). CONCLUSIONS: This study showed that LARC patients receiving pre-operative CRT tended to develop late LR more often than those receiving post-operative CRT. Further extended follow-up than is conventional may be necessary in LARC patients who are managed with optimized multimodal treatments, and the follow-up strategy may need to be individualized according to tumor location within the rectum.