NEOADJUVANT THERAPY AND SURGERY FOR RECTAL CANCER. Comparative study between partial and complete pathological response

Abstract

-Background -The approach of locally advanced extra-peritoneal rectal adenocarcinoma implies a treatment with neoadjuvant chemoradiotherapy associated with total mesorectal excision surgery. However, the tumors respond variably to this neoadjuvant therapy, and the mechanisms for response are not completely understood. Objective -Evaluate the variables related to the complete tumor response and the outcomes of patients who underwent surgery, comparing those with partial tumor regression and those with total remission of rectal lesion, at the pathological examination. Methods -Retrospective analysis of medical records of 212 patients operated between 2000 and 2010, in which 182 (85.9%) obtained partial remission at neoadjuvant therapy (Group 1) and 30 (14.1%), total remission (Group 2). Results -No difference was found between the groups in relation to gender, ethnicity, age, tumor distance from the anal verge, occurrence of metastases and synchronous lesions on preoperative staging, dose of radiotherapy and performed surgery. In Group 2, was verified high rate of complete remission when the time to surgery after neoadjuvant therapy was equal or less than 8 weeks (P=0.027), and a tendency of lower levels of pretreatment carcinoembryonic antigen (P=0.067). In pathological analysis, the Group 1 presented in relation to Group 2, more affected lymph nodes (average 1.9 and 0.5 respectively; P=0.003), more angiolymphatic (19.2% and 3.3%; P=0.032) and perineural involvement (15.4% and 0%; P=0.017) and greater number of lymph nodes examined (16.3 and 13.6; P=0.023). In the late follow-up, Group 1 also had lower overall survival than Group 2 (94.1 months and 136.4 months respectively; P=0.02) and disease-free survival (85.5 months and 134.6 months; P=0.004). There was no statistical difference between Group 2 and Group 1 in local recurrence (15% and 3.4%, respectively) and distant metastasis (28% and 13.8%, respectively). Conclusion -In this study, the only factor associated with complete remission of rectal adenocarcinoma was the time between neoadjuvant therapy and surgery. This group of patients had less affected lymph nodes, less angiolymphatic and perineural involvement, a longer overall and disease-free survival, but no significant statistical difference was observed in local recurrence and distant metastasis. Although the complete pathologic remission was associated with better prognosis, this not implied in the cure of the disease for all patients. HEADINGS -Neoadjuvant therapy. Colorectal surgery. Rectal neoplasms.

Pathological Complete Response After Neoadjuvant Therapy in Rectal Adenocarcinoma: a 5-Year Follow-up

“…Surgical resection is the cornerstone of curative management, with total mesorectal excision (TME) plays a fundamental role in patients who undergo rectal surgery [2][3][4]. With advancement in oncological therapies, neoadjuvant therapy prior to surgical resection of rectal cancer increased overall survival, disease-free survival, and reduced local recurrence rate [5,6]. Therefore, neoadjuvant therapy is now the gold standard of treatment for locally advanced mid and low rectal cancer before subjecting patients to curative surgery resection (with criteria of T3 and above, positive mesorectal nodes, mesorectal fascia involvement or when mesorectal fascia is threatened) [7].…”

Predicting Factors of Complete Pathological Response in Locally Advanced Rectal Cancer

“…The factors are size, grading and differentiation of tumor, tumor distance from the anal verge, serum CEA and fibrinogen level, blood cell counts, gap between neo-CRT and surgery, and many other proposed factors. 5 , 9 , 11 , 13 - 19 , 21 , 23 , 28 - 29 , 35 - 41 Also, some factors including involvement of lymph nodes at the beginning of disease, unfavorable tissue presentations like lymphovascular and perineural invasion, and high-grade tumors have been proposed to be associated with lymphatic system involvement even despite the achievement of cPR. 42 Even so, there is still no agreement on any of the above-mentioned factors regarding predictor factors of cPR and wait and watch policy in the treatment of rectal cancer.…”

“… 3 , 9 , 10 , 14 , 23 , 33 , 34 In recent years, many studies have tried to find the predicting factors of cPR following neo-CRT in rectal cancer. 5 , 9 , 11 , 13 - 19 , 21 , 23 , 28 , 29 , 35 - 42 Even so, there is still no agreement on any of the proposed factors regarding predictors of cPR and “wait and watch policy” in the treatment of rectal cancer. 3 , 12 , 15 , 17 , 19 , 20 , 28 , 31 , 33 , 38 , 43 - 45 Therefore, considering its importance, it is still a hot topic of research in rectal cancer treatment.…”

<p>Short-Term Clinical and Oncological Outcome of Prolonging Operation Interval After Neoadjuvant Chemoradiotherapy for Locally Advanced Middle and Low Rectal Cancer</p>

“…It has been proven that as the interval time increased within 12 weeks, the rate of tumor regression and pCR rate increased gradually, which would decrease over 12 weeks interval time. 14 De Andrade et al 41 performed a study which exhibited that interval time was the sole influencing factor of pathological complete remission, and prolonging interval time over 8 weeks would clearly increase the pathological complete remission rate. However, some other studies have shown that prolonging the interval time after nCRT did not increase pCR; instead, this would increase postoperative complications and the occurrence of distant metastasis during the waiting period.…”