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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

Nahas, Sergio Carlos M.D., Ph.D.; Rizkallah Nahas, Caio Sergio M.D., Ph.D.; Sparapan Marques, Carlos Frederico M.D.; Ribeiro, Ulysses Jr M.D., Ph.D.; Cotti, Guilherme Cutait M.D.; Imperiale, Antonio Rocco M.D.; Capareli, Fernanda Cunha M.D.; Chih Chen, Andre Tsin M.D.; Hoff, Paulo M. M.D., Ph.D.; Cecconello, Ivan M.D., Ph.D.

Diseases of the Colon & Rectum: April 2016 - Volume 59 - Issue 4 - p 255–263
doi: 10.1097/DCR.0000000000000558
Original Contributions: Colorectal/Anal Neoplasia

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.7–19

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,

Supplemental Digital Content is available in the text.

Hospital das Clínicas da Faculdade de Medicina, Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo, Brazil

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML and PDF versions of this article on the journal’s Web site (

Financial Disclosure: None reported.

Podium presentation at the meeting of The American Society of Colon and Rectal Surgeons, Boston, MA, May 30 to June 3, 2015.

Correspondence: Sergio Carlos Nahas, M.D., Ph.D., “Octávio Frias de Oliveira,” São Paulo Cancer Institute, São Paulo, Brazil. E-mail:

© 2016 The American Society of Colon and Rectal Surgeons