Objective: To evaluate the safety and preliminary efficacy of total
neoadjuvant therapy (
TNT) in patients with locally advanced
rectal cancer (LARC) with high risk factors. Methods: Data of 101 patients who were diagnosed with stage II-III
rectal cancer with high risk factors and received
TNT between March 2015 and January 2018 at West China Hospital of Sichuan University were analyzed retrospectively. Inclusion criteria: (1) patients were diagnosed with stage II-III
rectal cancer by high-resolution MRI combined with CT and endorectal ultrasound; (2) at least one high risk factor: cT4a, cT4b, cN2, EMVI+, CRM+ and lateral lymph node+; (3) distance from
tumor to anal verge was within 15 cm; (4) Eastern Collaborative Oncology Group (ECOG) performance status score was 0-1; bone marrow function, liver function and kidney function were suitable for
chemoradiotherapy; (5) patients were treated with
TNT strategy; (6) the follow-up data and postoperative pathological data were complete. Patients with previous
rectal cancer surgery (except prophylactic
colostomy), pelvic
radiotherapy, and systemic
chemotherapy, those with distant
metastases, those without
neoadjuvant radiotherapy, those receiving less than 4 cycles of
neoadjuvant chemotherapy were excluded. The regimen of
TNT: 3 cycles of induction CAPOX (
oxaliplatin plus
capecitabine) were followed by pelvic
radiotherapy and concurrent CAPOX, then 3 cycles of consolidation CAPOX were delivered after
radiotherapy. Total mesorectal resection (TME) or watch-and-wait strategy was selected according to the
therapeutic effect and patients' wishes. Short-term efficacy, including
tumor regression grade (TRG), pathological complete response (pCR), clinical complete response (cCR), postoperative complications within 30 days of surgery, and adverse events (AE) to
radiotherapy and
chemotherapy (measured using CTCAE 4.0) was analyzed. Results: The 101 patients included 68 males (67.3%) and 33 females (32.7%) with a median age of 54 years. The proportion of patients with cT4a, cT4b, cN2 and enlarged lateral lymph node was 13.9%, 29.7%, 56.4% and 43.6%, respectively. The mean cycle of
neoadjuvant chemotherapy was 6.0±1.3. Seventy-five patients (74.3%) received at least 6 cycles of
neoadjuvant chemotherapy and 100 (99.0%) completed
radiotherapy. The mean cycle of induction and
consolidation chemotherapy was 2.0±0.9 and 2.8±1.0 respectively. Most common grade 3 AE was leucopenia (n=13, 12.9%) and
thrombocytopenia (n=7, 6.9%). Grade 3
diarrhea and radiation
dermatitis were observed in 5 cases (5.0%) respectively. Grade 3
anemia and rectal
pain were observed in 4 cases (4.0%) respectively. And rectal
mucositis was observed in 2 cases (2.0%). Most of the AE was observed during
concurrent chemoradiotherapy. No grade 4 or higher AE was observed. After
TNT, 32 patients (31.7%) achieved pCR or cCR, and 62 patients (60.4%) achieved partial response (PR). Only 2 patients (2.0%) developed distant
metastasis after
chemoradiotherapy, while the other patients did not show
disease progression. Seven patients (6.9%) with cCR refused surgery and selected watch-and-wait, while 7 patients without cCR still refused surgery. The other 87 patients (86.1%) underwent TME successfully. The mean interval from the completion of
chemoradiotherapy to surgery was (20.1±8.5) weeks. The R0 resection rate was 97.7% (85/87).The morbidity of surgical complication was 16.1% (14/87), including
pelvic infection or
abscess in 6 cases (6.9%),
anastomotic leakage in 3 (3.4%),
hemorrhage in 2 (2.3%), and gastrointestinal dysfunction in 3 (3.4%). Pathological findings revealed that 24 cases (27.6%) had TRG 0, 20 (23.0%) had TRG 1, 30 (34.5%) TRG 2, and 13 (14.9%) TRG 3. Conclusion:
TNT is safe and has good short-term efficacy for locally advanced
rectal cancer patients with high risk factors.