Upfront Systemic Chemotherapy and Short-Course Radiotherapy with Delayed Surgery for Locally Advanced Rectal Cancer with Distant Metastases: Outcomes, Compliance, and Favorable Prognostic Factors

PLoS One. 2016 Aug 18;11(8):e0161475. doi: 10.1371/journal.pone.0161475. eCollection 2016.

Abstract

Purpose/objective(s): Optimal treatment for locally advanced rectal cancer (LARC) with distant metastasis remains elusive. We aimed to evaluate upfront systemic chemotherapy and short-course radiotherapy (RT) followed by delayed surgery for such patients, and to identify favorable prognostic factors.

Materials/methods: We retrospectively reviewed 50 LARC patients (cT4 or cT3, <2 mm from the mesorectal fascia) with synchronous metastatic disease. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival, treatment-related toxicity, and compliance. We considered P values <0.05 significant.

Results: At 22 months median follow-up, the median PFS time was 16 months and the 2-year PFS rate was 34.8%. Thirty-five patients who received radical surgery for primary and metastatic tumors were designated the curable group. Six patients with clinical complete response (ypCR) of metastases who underwent radical surgery for only the primary tumor were classified as potentially curable. Nine patients who received no radical surgery (3 received palliative surgery) were deemed the palliative group. The ypCR rate among surgery patients was 13.6%. PFS rates for the curable or potentially curable groups were significantly longer than that of the palliative group (P<0.001). On multivariate analysis, solitary organ metastasis and R0 status were independent prognostic factors for PFS.

Conclusions: These findings demonstrated that a strong possibility that upfront chemotherapy and short-course RT with delayed surgery are an effective alternative treatment for LARC with potentially resectable distant metastasis, owing to achievement of pathologic down-staging, R0 resection, and favorable compliance and toxicity, despite the long treatment duration.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use
  • Combined Modality Therapy / methods
  • Disease-Free Survival
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • Rectal Neoplasms / diagnosis
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / therapy*
  • Rectum / surgery
  • Retrospective Studies
  • Survival Analysis

Substances

  • Antineoplastic Agents

Grants and funding

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2015R1C1A1A01053547).