Timing of Radiation Therapy, Lymph Node Retrieval, and Survival in Rectal Cancer

Background: Lymph node retrieval is an independent prognostic factor for survival in rectal cancer. Preoperative radiotherapy has been shown to impact the number of lymph nodes retrieved.

Objective: This study aimed to analyze colorectal cancer-specific mortality and overall mortality associated with the number of lymph nodes retrieved in relation to use and timing of radiotherapy.

Design: This study was designed as a retrospective analysis.

Settings: Analysis of the California Cancer Registry was conducted.

Patients: Patients with rectal cancer from 1994 to 2006 with a follow-up until January 2008 were included.

Main Outcome Measures: The number of lymph nodes (1-3, 4-6, 7-11, ≥ 12) stratified by stage (I, II, and III) was analyzed based on radiotherapy status (no radiotherapy, preoperative radiotherapy, and postoperative radiotherapy). Multivariate colorectal cancer-specific survival and overall mortality analyses were performed using Cox proportional-hazard ratios.

Results: A total of 17,670 incident cases of stage I, II, and III rectal cancer were identified. The number of lymph nodes retrieved in cases receiving preoperative radiotherapy was lower than others. In stage II cases receiving preoperative radiotherapy, retrieval of 7 to 11 lymph nodes (compared with 0 lymph nodes retrieved as a reference) reached the nadir of colorectal cancer-specific mortality benefit (HR = 0.39, 95% CI, 0.28-0.56) and overall mortality (HR = 0.62, 95% CI, 0.48-0.80). In stage II cases with no radiotherapy or postoperative radiotherapy, retrieval of ≥ 12 lymph nodes remained the strongest prognosticator of colorectal cancer-specific mortality (HR = 0.34, 95% CI, 0.25-0.46; HR = 0.36, 95% CI, 0.24-0.53 respectively).

Limitations: : The California Cancer Registry does not include radiation dose and duration, chemotherapy type and dosage, margin status and surgeon characteristics, and stated reasons for lower number of lymph nodes retrieved or patient-related factors. In addition, no central pathology laboratory was used.

Conclusions: In stage II rectal cancer cases receiving preoperative radiotherapy vs either postoperative or no radiotherapy, a lower threshold of lymph node retrieval may be sufficient to evaluate prognosis and to guide further therapy.