Significance of perineural and lymphovascular invasion in locally advanced rectal cancer treated by preoperative chemoradiotherapy and radical surgery: Can perineural invasion be an indication of adjuvant chemotherapy?

PURPOSE: To investigate the prognostic significance of lymphovascular space invasion (LVI) and perineural invasion (PNI) in rectal cancer. METHODS AND MATERIALS: Clinical data of 1,232 stage II-III rectal cancer patients from six tertiary institutions were analyzed. All patients were treated by long-course preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME). Adjuvant systemic chemotherapy was performed for 962 (78.1%) patients according to the multidisciplinary team's decision. Treatment outcomes and prognostic factors were evaluated according to the lymphovascular invasion (LVI) and perineural invasion (PNI) status.
RESULTS: Five-year overall survival (OS) and recurrence-free survival (RFS) rates of the entire cohort were 84.1% and 71.1%, respectively. There is a significant difference in 5-year OS among both-absent, LVI+ only, PNI+ only, and both-present groups (89.1% vs. 77.9% vs. 67.6% vs. 56.2%; p < 0.001). RFS at five years was significantly different among both-absent, LVI+ only, PNI+ only, and both-present groups (78.7% vs. 58.7% vs. 44.6% vs. 38.6%; p < 0.001). The 5-year distant failure-free survival (DFFS) rate was also significantly different among four groups (84.6% vs. 61.4% vs. 54.2% vs 48.6%; p < 0.001). Although adjuvant chemotherapy did not affect 5-year DFFS in the entire cohort, adjuvant chemotherapy significantly reduced the distant failure rate in patients with PNI+ patients (44.9% vs. 54.6%, p = 0.048), not LVI+ patients (65.0% vs. 56.1%, p = 0.487).
CONCLUSION: Compared to LVI, PNI is a more significant prognostic factor in stage II-III rectal patients treated by preoperative CRT and TME surgery. The status of PNI rather than LVI could be an indicator for identifying patients who could benefit from adjuvant systemic chemotherapy.