Preoperative Chemo-radiotherapy For T3 Stage Rectal Cancer Patients: Long-term Outcome Of Multimodality Management And Implications For Risk-adapted Treatment Strategies

Abstract

Preoperative chemoradiotherapy (preop-CRT) followed by total mesorectal excision (TME) is considered standard of care for T3 N0-2, mid-low rectal cancer. Evolving approaches include new drug-radiation modality combinations aimed to increase tumor response, the ability to perform a sphincter-saving surgery and to improve disease control and patient survival. This study analyses potential predictive factors for tumor downstaging (DWS) and pathologic complete response (pCR), and long-term results of T3 rectal cancer patients (pts) treated by preop-CRT in relation to pathologic response, surgical treatment and other treatment variables including IORT and adjuvant CT. Between 1994 and 2007, 133 pts (M/F:89/54; median age 60 yrs, 27-79) with T3N0 (42%) or N1-2(58%)M0 rectal cancer received preop-CRT. Median RT dose was 50.4 Gy (45-55Gy) with concurrent CT by several protocols (bolus FU-LV, ci FU +/- Gefitinib, Raltitrexed, and Capecitabine +/- Oxaliplatin). TME was performed in 114pts (LAR: 90; APR: 17, whereas 26 pts (19%) underwent full-thickness local excision (LE) for several reasons. A cohort of 40 pts (30%) received IORT to high-risk area by study protocol and 30 pts (22%) received adjuvant CT (pN+). Mandard score was used for tumor regression grade (TRG) evaluation. Of 133 pts, tumor DWS was reported in 74% and pCR in 31% of pts. TRG1-2 was reported in 60% of pts. Univariate analysis of clinical factors including age, gender, N stage, distance from anal verge, RT dose and CT regimens, indicates only the N1-2 factor significantly associated with lower DWS rates (p = 0.009, OR 0.34). At a median follow-up of 54 months, 5-yrs OS, DFS and LDFS were 78.%, 75% and 88%, respectively. Of treatment and pathologic evaluated parameters, pCR and TRG1-2 demonstrated a significant better outcome. In pCR pts, no differences in outcome were observed by type of surgery (TME vs LE). Significantly better local control results were reported in N1-2 and TRG 3-5 pts who underwent IORT. Our results indicate that N1-2 clinical stage can predict pathologic response to Preop-CRT. Pts with pCR or TRG1-2 have a favorable long-term outcome, therefore exploring the LE approach for these patients may be warranted. IORT is of benefit in a subset of patients with N1-2 or TRG 3-5. These findings may be considered for risk-adapted treatment strategies in T3 rectal cancer patients as well as to address novel treatment approaches.