Pathologic Complete Response in Rectal Cancer: Can We Detect It? Lessons Learned From a Proposed Randomized Trial of Watch-and-Wait Treatment of Rectal Cancer.

BACKGROUND: Chemoradiotherapy has the potential to downsize and downstage tumors before surgery, decrease locoregional recurrence, and induce a complete sterilization of tumor cells for middle and low locally advanced rectal cancer. A watch-and-wait tactic has been proposed for patients with clinical complete response.

OBJECTIVE: The purpose of this study was to verify our ability to identify complete clinical response in patients with rectal cancer based on clinical and radiologic criteria.

DESIGN: This was a prospective study.

SETTINGS: The study was conducted at a single institution, in the setting of a watch-and-wait randomized trial.

PATIENTS: Consecutive patients with stage T3 to T4N0M0 or T(any)N+M0 cancer located within 10 cm from anal verge or T2N0 within 7 cm from anal verge were included in the study. Patients were staged and restaged 8 weeks after completion of chemoradiation (5-fluorouracil, 5040 cGy) by digital examination, colonoscopy, pelvic MRI, and thorax and abdominal CT scans.

MAIN OUTCOME MEASURES: Clinical and radiologic judgments of tumor response were compared with pathologic response of patients treated by total mesorectal excision or clinical follow-up of patients selected for nonoperative treatment.

RESULTS: A total of 118 patients were treated. Six patients were considered clinic complete responders (2 randomly assigned for surgery (1 ypT0N0 and 1 ypT2N0) and 4 patients randomly assigned for observation (3 sustained clinic complete response and 1 had tumor regrowth)). The 112 clinic incomplete responders underwent total mesorectal excision, and 18 revealed pathologic complete response. These 18 patients were not considered complete responders at restaging because they presented at least 1 of the following conditions: mucosal ulceration and/or deformity and/or substenosis of rectal lumen at digital rectal examination and colonoscopy (n = 16), ymrT1 to T4 (n = 16), ymrN+ (n = 2), involvement of circumferential resection margin on MRI (n = 3), extramural vascular invasion on MRI (n = 4), MRI tumor response grade 2 to 4 (n = 15), and pelvic side wall lymph node involvement on MRI (n = 1). Sensitivity for identification of ypT0N0 or sustained clinic complete response was 18.2%.

LIMITATIONS: This study has a short follow-up and small sample size. Radiologists who reviewed the restaging examination were not blinded to the pretreatment stage. Only 1 radiologist read the images of each patient.

CONCLUSIONS: Evaluation of clinic complete response according to current adopted criteria has low sensitivity because pathologic complete response more frequently presented as clinic incomplete response (see Video, Supplemental Digital Content 1, https://links.lww.com/DCR/A221).