Neoadjuvant therapy and surgery in rectal adenocarcinoma: analysis of patients with complete tumor remission (original) (raw)
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Cancer Biology & Medicine
Objective: To assess the response rate of patients with rectal adenocarcinoma to neoadjuvant therapy and to identify the predictors of histological regression after neoadjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Methods: This study recruited 64 patients. The patients had resectable cancer of the lower and the middle rectum (T3/T4 and/or N+) without distant metastasis and received neoadjuvant RT or CCRT followed by radical surgery with total mesorectal excision (TME) between January 2006 and December 2011. The patients were classified into non-response (NR), partial response (PR), and pathologic complete response (pCR) based on the Dworak tumor regression grading system. Results: The median age of patients was 57 years (ranging from 22 to 85). A total of 24 patients were treated with neoadjuvant CCRT, whereas 40 patients were treated with RT alone. Abdominoperineal resection (APR) was performed on 29 patients (45%). Anterior resection with TME was performed on 34 patients (53%). One patient had local resection. Histologically, 12 (19%), 24 (73%), and 28 (44%) patients exhibited pCR, PR, and NR, respectively. Univariate analysis revealed that the predictors of tumor regression were as follows: the absence of lymph node involvement from initial imaging (cN0) (P=0.021); normal initial carcinoembryonic antigen (CEA) level (P=0.01); hemoglobin level ≥12 g/dl (P=0.009); CCRT (P=0.021); and tumor downstaging in imaging (P=0.001). Multivariate analysis showed that the main predictors of pCR were CT combined with neoadjuvant RT, cN0 stage, and tumor regression on imaging. Conclusions: Identifying the predictors of pCR following neoadjuvant therapy aids the selection of responsive patients for nonaggressive surgical treatment and possible surveillance.
BJS open, 2022
Background: The optimal timing of surgery following chemoradiotherapy (CRT) is controversial. This trial aimed to assess disease recurrence and survival rates between patients with locally advanced rectal adenocarcinoma (LARC) who underwent total mesorectal excision (TME) after a waiting interval of 8 weeks or less (classic interval; CI) versus more than 8 weeks (long interval; LI) following preoperative CRT. Methods: This was a phase III, single-centre, randomized clinical trial. Patients with LARC situated within 12 cm of the anal verge (T3-T4 or N+ disease) were randomized to undergo TME within or after 8 weeks after CRT. Results: Between January 2006 and January 2017, 350 patients were randomized, 175 to each group. As of February 2022, the median follow-up time was 80 (6-174) months. Among the 322 included patients (CI, 159; LI, 163) the cumulative incidence of locoregional recurrence at 5 years was 10.1 per cent in the CI group and 6.9 per cent in the LI group (P = 0.143). The cumulative incidence of distant metastasis at 5 years was 30.8 per cent in the CI group and 18.6 per cent in the LI group (sub-HR = 1.78; 95 per cent c.i. 1.14 to 2.78, P = 0.010). The disease-free survival (DFS) in each group was 59.7 and 69.9 per cent respectively (P = 0.157), and overall survival (OS) rates at 5 years were 73.6 versus 77.9 per cent (P = 0.476). Conclusion: Incidence of distant metastasis decreased with an interval between CRT and surgery exceeding 8 weeks, but this did not impact on DFS or OS.
World Journal of Surgery, 1999
Preoperative radiation therapy (PRT) prior to potential curative resection for rectal adenocarcinoma is not widely accepted. This report evaluates the prognostic factors affecting local recurrence and 5-year survival. This is a retrospective study of 214 patients with primary rectal adenocarcinoma treated from January 1986 to December 1994. A PRT dosage of 45 Gy in 20 fractions was administered to patients with clinically tethered or fixed tumors, and 4 to 8 weeks later surgery was performed (group I). Patients with clinically mobile tumors were treated by surgery alone (group II). There were 130 men and 84 women. The median age was 58 years (range 19 -85 years). There were 111 patients in group I: 7 patients had no microscopic residual tumor, 80 had Dukes' A and B, and 24 had Dukes' C. There were 103 patients in group II: 70 patients were classified as Dukes' A and B and 33 as Dukes' C. The mean follow-up of the entire cohort was 62 months (range 2-132 months). Local recurrence was seen in 17% of patients in group I and 35% in group II (p ؍ 0.002). Distant recurrence in patients with metastatic lymph nodes was seen in 79% of group I and in 34% of group II (p ؍ 0.001). The favorable prognostic factors for local control were the administration of PRT and well differentiated cancer. The favorable prognostic factors for survival were age < 50 years and the absence of lymph node metastasis. The administration of PRT diminishes the risk of local recurrence. The presence of metastatic lymph nodes in the postirradiated specimen is an ominous prognostic factor for survival. Therefore such patients should be considered for adjuvant chemotherapy. Correspondence to: P. Luna-Pérez, M.D., Puerto México 53-101, Col. Roma, México D.F., Mexico CP 06760
Diseases of the Colon & Rectum, 2020
BACKGROUND: Current guidelines for locally advanced stage 2/3 rectal cancer recommend neoadjuvant chemoradiotherapy followed by total mesorectal excision and adjuvant chemotherapy. The oncologic benefit of adjuvant chemotherapy has not been consistently demonstrated. OBJECTIVE: The purpose of this study was to evaluate disease recurrence and survival in patients with rectal cancer who received adjuvant chemotherapy after chemoradiotherapy and total mesorectal excision. DESIGN: This was a retrospective review of patients with stage 2/3 rectal cancer after chemoradiotherapy and surgery, based on receipt of adjuvant chemotherapy. SETTINGS: The study was conducted at the Kaiser Permanente Southern California system of 14 hospitals and associated clinics. PATIENTS: A total of 862 patients with stage 2/3 rectal cancer diagnosed and treated between January 1, 2005, and December 31, 2016, were included in this study. INTERVENTIONS: The study involved neoadjuvant chemoradiotherapy followed by total mesorectal excision with or without adjuvant chemotherapy. MAIN OUTCOME MEASURES: The primary end point was recurrence-free survival. RESULTS: A total of 348 stage 2 and 514 stage 3 patients were included; 660 patients (76.6%) underwent adjuvant chemotherapy. Mean patient follow-up after surgery was 63.0 months (range, 3-160). Multivariable analysis showed that yp stage (HR for yp stage 2 = 4.74; yp stage 3 = 8.83) and en bloc resection (HR = 1.76) were the only variables that significantly predicted disease recurrence. Neither pretreatment tumor stage nor receipt of adjuvant chemotherapy was significantly associated with recurrencefree survival. Log-rank testing failed to demonstrate significant recurrence-free survival improvement after receipt of adjuvant chemotherapy in any patient subgroup. LIMITATIONS: The study was limited by selection bias attributed to the nature of a retrospective study without patient randomization or predefined treatment protocol.
Pre- and Post-Surgery Treatments in Rectal Cancer: A Long-Term Single-Centre Experience
Current Oncology, 2017
Background Our study evaluated long-term survival outcomes in rectal cancer patients treated with preoperative radiotherapy, and the impact on survival of concomitant and postoperative adjuvant chemotherapy (ctx), among other prognostic factors. Methods The study included 196 patients [median age: 58 years (range: 20-86 years); 63.0% men] with locally advanced rectal carcinoma and, in some cases, resectable liver metastasis. Rates of distant metastasis and local recurrence and of 5-year distant metastasis-free survival (dmfs) and overall survival (os) were determined. Results The 5-year os rate was 57.0%, with a median duration of 81.5 months (95% confidence interval: 73.7 months to 89.4 months), and the 5-year dmfs rate was 54.1%, with a median duration of 68.4 months (95% confidence interval: 40.4 months to 96.4 months). Prognostic factors for higher os and dmfs rates were downstaging (p = 0.013 and p = 0.005 respectively), radiotherapy dose (50 Gy vs. 56 Gy or 45-46 Gy, both p = 0.002), and concomitant ctx use (p = 0.004 and p = 0.001) and type (5-fluorouracil-leucovorin-folinic acid vs. tegafur-folinic acid, p = 0.034 and p = 0.043). Adjuvant ctx after neoadjuvant long-term concomitant chemoradiotherapy (ccrt) and surgery was associated with better 5-year os rates for postoperative T0-T3 disease (p = 0.003) and disease at all lymph node stages (p = 0.001). Conclusions Our findings revealed a favourable survival outcome with long-term fractionated irradiation and concomitant 5-fluorouracil-based ctx, achieving 5-year os and dmfs rates of 57.0% and 54.1% respectively. Preoperative administration of radiotherapy (50 Gy) and postoperative adjuvant ctx were associated with a significant survival benefit. Radiation doses above 50 Gy and the interval between ccrt and surgery had no significant effect on survival.
Surgery, 2009
Background. Our objective was evaluate the outcome of primary clinical T4M0 extraperitoneal rectal cancer treated by neoadjuvant radiochemotherapy. Prognosis of clinical T4 rectal cancer is poor. Preoperative chemoradiation therapy may be beneficial. The results obtained are unclear due to lack of objective and strictly applied staging methods. Methods. Patients with primary, clinical, T4MO, extraperitoneal rectal cancer, defined by transrectal ultrasonography, computed tomography or magnetic resonance imaging, were considered. Intraoperative radiotherapy and adjuvant chemotherapy were employed in some patients after curative resection (R0). Variables influencing the possibility to perform an R0 resection and a sphincter-saving procedure were investigated as predictors of outcome. Results. 100 patients were included. R0 resection was performed in 78 patients. R0 resection rate was greater in females (93% vs 67%) and in responders to neoadjuvant chemoradiation (94% vs 60%). The ability to perform a sphincter-saving procedure was 57%, greater in middle rectal location (85% vs 51%) and in responders to the chemoradiation (70% vs 47%). Median follow-up was 31 months (range, 4--136). Local recurrences were found in 7 patients (10%). Five-year local control in R0 patients was 90% and better in the IORT group (100%). Distant relapse occurred in 24 patients (30%). Five-year overall survival was 59%, and was better after an R0 versus an R1 or R2 resection (68% vs 22%). Overall and disease free survival in R0 patients improved after overall downstaging. Adjuvant chemotherapy given in addition to the neoadjuvant therapy did not appear to offer benefit in improving survival. Conclusion. A multimodal approach enabled us to obtain a 5-year overall survival of about 60%. IORT increased local control. The role of adjuvant chemotherapy needs to be further investigated. (Surgery 2009;145:486-94.) From the
BMC Cancer, 2013
Background: Neoadjuvant radiochemotherapy (RCT) is now part of the armamentarium of cancer of the lower and middle rectum. It is recommended in current clinical practice prior to surgical excision if the lesion is classified T3/T4 or N+. Histological complete response, defined by the absence of persistent tumor cell invasion and lymph node (ypT0N0) after pathological examination of surgical specimen has been shown to be an independent prognostic factor of overall survival and disease-free survival. Surgical excision is usually performed between 6 and 8 weeks after completion of CRT and pathological complete response rate ranges around 12%. In retrospective studies, a lengthening of the interval after RCT beyond 10 weeks was found as an independent factor increasing the rate of pathological complete response (between 26% and 31%), with a longer disease-free survival and without increasing the operative morbidity. The aim of the present study is to evaluate in 264 patients the rate of pathological complete response rate of rectal cancer after RCT by lengthening the time between RCT and surgery.
Arquivos de gastroenterologia
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. 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. 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). 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...
Diseases of the Colon & Rectum, 2013
BACKGROUND: neoadjuvant chemoradiotherapy followed by total mesorectal excision has improved the outcome of locally advanced rectal carcinoma. OBJECTIVE: the aim of this study was to identify independent prognosis factors of disease recurrence in a group of patients treated with this approach. DESIGN AND PATIENTS: this study was retrospective in design. Data from patients with locally advanced rectal cancer who had completed treatment from 2000 to 2010 were reviewed. SETTINGS: the analysis was performed in a tertiary referral center. MAIN OUTCOME MEASURES: the primary outcomes measured were the recurrence risk factors. RESULTS: the cohort consisted of 228 patients; 69.3% of them were men, and median age was 59 years. stage iii rectal cancer was found in 64.9% of patients. the most frequently administered therapy was concurrent capecitabine, oxaliplatin, and 7-field radiotherapy, followed by 3-field radiotherapy and fluoropyrimidines. after a median follow-up of 49 months, 23.7% of the patients experienced disease recurrence: 2.6% had local recurrence, 21.1% had distant metastases, and 0.5% had both. factors significantly correlated with recurrence risk in multivariate logistic regression were y-pathological stage (iii vs i/ii: oR = 2.51), tumor regression grade (1/2 vs 3+/4: oR = 3.34; 3 vs 3+/4: oR = 1.20), and low rectal location (oR = 2.36). the only independent prognosis factor for liver metastases was tumor regression grade (1/2 vs 3+/4: oR = 4.67; 3 vs 3+/4: oR = 1.41), whereas tumor regression grade (1-2 vs 3+/4: oR = 5.5; 3 vs 3+/4: oR = 1.84), low rectal location (oR = 3.23), and previous liver metastasis (oR = 7.73) predicted lung recurrence. LIMITATIONS: this is a single institutional experience, neoadjuvant combined therapy is not homogeneous, and the analysis has been performed in a retrospective manner. CONCLUSIONS: Patients with low third locally advanced rectal cancer with a poor response to neoadjuvant chemoradiotherapy (high y-pathological stage or low tumor regression grade) are at high risk of recurrence. intense surveillance and the design of alternative therapeutic approaches aimed to lower the distant failure rate seem warranted.