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Perineural Invasion Predicts for Distant Metastasis in Locally Advanced Rectal Cancer Treated With Neoadjuvant Chemoradiation and Surgery

Chablani, Priyanka MS*; Nguyen, Phuong MD*; Pan, Xueliang PhD; Robinson, Andrew BA*; Walston, Steve DO*; Wu, Christina MD; Frankel, Wendy L. MD§; Chen, Wei MD§; Bekaii-Saab, Tanios MD; Chakravarti, Arnab MD*; Wuthrick, Evan MD*; Williams, Terence M. MD, PhD*

American Journal of Clinical Oncology: December 2017 - Volume 40 - Issue 6 - p 561–568
doi: 10.1097/COC.0000000000000214
Original Articles: Gastrointestinal

Objectives: The benefit of adjuvant chemotherapy in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT) and surgery is controversial. We examined the association of perineural invasion (PNI) with outcomes to determine whether PNI could be used to risk-stratify patients.

Materials and Methods: We performed a retrospective study of 110 patients treated with nCRT and surgery for LARC at our institution from 2004 to 2011. Eighty-seven patients were identified in our final analysis. We evaluated the association of PNI with locoregional control, distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival, using log-rank and Cox proportional hazard modeling.

Results: Fourteen patients (16%) were PNI+ and 73 patients (84%) were PNI−. The median follow-up was 27 months (range, 0.9 to 84 mo). The median DMFS was 13.5 months for PNI+ and median not reached (>40 mo) for PNI− (P<0.0001). The median DFS was 13.5 months for PNI+ and 39.8 months for PNI− (P<0.0001). In a multivariate model including 7 pathologic variables, type of surgery, time to surgery from end of nCRT, and use of adjuvant chemotherapy, PNI remained a significant independent predictor of DMFS (hazard ratio 9.79; 95% confidence interval, 3.48-27.53; P<0.0001) and DFS (hazard ratio 5.72; 95% confidence interval, 2.2-14.9; P=0.0001).

Conclusions: For patients with LARC treated with nCRT, PNI found at the time of surgery is significantly associated with worse DMFS and DFS. Our data support testing the role of adjuvant chemotherapy in patients with PNI and perhaps other high-risk features.

Supplemental Digital Content is available in the text.

*Department of Radiation Oncology

Center for Biostatistics

Department of Internal Medicine, Division of Medical Oncology

§Department of Pathology, The Ohio State University, Columbus, OH

This research was presented at the Gastrointestinal Cancers Symposium 2015 (San Francisco, CA).

The authors declare no conflicts of interest.

Reprints: Terence M. Williams, MD, PhD, and Evan Wuthrick, MD, Department of Radiation Oncology, The Ohio State University, 460 West 10th Ave., Columbus, OH 43210. E-mails:;

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