Post-treatment TNM staging is a prognostic indicator of survival and recurrence in tethered or fixed rectal carcinoma after preoperative chemotherapy and radiation

Abstract

Purpose/Objective: Preoperative chemotherapy and radiation is given in locally advanced (T3/T4) rectal cancer to improve tumor resectability, sphincter-sparing and tumor control. If an adequate interval is allowed between radiation and surgical resection for tumor downstaging, the post-chemoradiation TNM staging can be an indicator of tumor response to neoadjuvant therapy, which might be prognostic of outcome. In this study, we evaluated whether this post-treatment TNM staging is predictive of survival and recurrence. Materials/Methods: Between 1993 and 2000, 128 patients with tethered or fixed M0 rectal cancer were treated with preoperative 50 Gy pelvic radiation concurrent with 2 cycles of 5-FU infusion and leucovorin (on days 1–4, 22–25) and a single bolus mitomycin C (on day 1). Another cycle of bolus 5FU/leucovorin was given at week 4, followed by surgical resection at week 8 after pelvic radiation. Additional postoperative chemotherapy was given after patients have recovered from their surgery. There were 93 males and 35 females. The median age was 62 years (30–79 years). There were 56 low- (1–5 cm), 66 mid- (6–10 cm) and 6 high- (>10 cm) rectal cancers. Clinically, 103 patients had a T3 and 25 patients had a T4 tumor. Ninety-three patients (73%) had pretreatment endorectal ultrasound assessment and they all had uT3 disease. All 128 patients underwent resection after completing their planned preoperative chemoradiation. 56 patients had an abdominoperineal resection and 72 patients had an anterior resection. Results: The post-chemoradiation pathological TNM staging was as follow: 32 Stage 0 (T0N0M0), 37 Stage I, 26 Stage II, 28 Stage III and 5 stage IV. 32 patients have achieved a pathological complete response (25%). 79 patients had the primary tumor downstaged to pT0-2 (62%). Thirty-five patients had pT3 and 14 patients had pT4 disease after chemoradiation. Positive lymph node metastasis was found in 31 patients (24%). Lymphovascular or neural invasion was present in 13 patients (10%). The median follow-up was 5 years for those patients who are still alive. As of February 2003, 80 patients are alive without disease and 4 are alive with disease. 32 patients had died from recurrence and 9 patients had died without recurrence. 3 patients were lost to follow-up (all NED). The overall 5-year disease-specific survival was 74% and the 5-year relapse-free survival was 71%. The overall local control rate was 92% at 5 years. When the patients were grouped according to their post-chemoradiation TNM stage, the 5-year survival was 97% for Stage 0, 88% for Stage I, 74% for Stage II, 44% for Stage III and 0% for Stage IV (p = 0.0000059). The 5-year relapse-free survival was 97% for Stage 0, 80% for Stage I, 72% for Stage II, 42% for Stage III and 0% for Stage IV (p <0.000001). Positive lymph node metastasis was a strong indicator of recurrence. The 5-year recurrence rate was 62% for pN1-2 versus 19% for pN0 (p = 0.000013). Another adverse factor was lymphovascular and/or neural invasion which was associated with a recurrence rate of 71% at 5 year, versus 24% for those patients without lymphovascular or neural invasion (p = 0.0026). The 5-year local control rate was 100% for Stage 0, 96% for Stage I, 87% for Stage II and 82% for Stage III (p = 0.17). Persistent T4 and T3 (to a lesser degree) disease was associated with a higher risk of local recurrence. The 5-year local control rate was 100% for pT0 and pT1, 95% for pT2, 89% for pT3 and 65% for pT4 (p = 0.0025). Conclusions: Post-neoadjuvant therapy TNM staging provides a useful evaluation of the tumor response to preoperative chemoradiation and it is a prognostic indicator of both survival and relapse-free survival. Positive lymph node metastasis, lymphovascular and neural invasion are adverse histopathological features associated with a higher risk of distant failure. Preoperative chemotherapy and 50 Gy of radiation can provide a good local control (92%) but persistent T4 disease is indicative of an increased risk of local recurrence.