Summary Background Organ preservation is a concept proposed for patients with rectal cancer after a good clinical response to neoadjuvant chemotherapy, to potentially avoid morbidity and side-effects ...of rectal excision. The objective of this study was to compare local excision and total mesorectal excision in patients with a good response after chemoradiotherapy for lower rectal cancer. Methods We did a prospective, randomised, open-label, multicentre, phase 3 trial at 15 tertiary centres in France that were experts in the treatment of rectal cancer. Patients aged 18 years and older with stage T2T3 lower rectal carcinoma, of maximum size 4 cm, who had a good clinical response to neoadjuvant chemoradiotherapy (residual tumour ≤2 cm) were centrally randomly assigned by the surgeon before surgery to either local excision or total mesorectal excision surgery. Randomisation, which was done via the internet, was not stratified and used permuted blocks of size eight. In the local excision group, a completion total mesorectal excision was required if tumour stage was ypT2–3. The primary endpoint was a composite outcome of death, recurrence, morbidity, and side-effects at 2 years after surgery, to show superiority of local excision over total mesorectal excision in the modified intention-to-treat (ITT) population (expected proportions of patients having at least one event were 25% vs 60% for superiority). This trial was registered with ClinicalTrials.gov , number NCT00427375. Findings From March 1, 2007, to Sept 24, 2012, 186 patients received chemoradiotherapy and were enrolled in the study. 148 good clinical responders were randomly assigned to treatment, three were excluded (because they had metastatic disease, tumour >8 cm from anal verge, and withdrew consent), and 145 were analysed: 74 in the local excision group and 71 in the total mesorectal excision group. In the local excision group, 26 patients had a completion total mesorectal excision. At 2 years in the modified ITT population, one or more events from the composite primary outcome occurred in 41 (56%) of 73 patients in the local excision group and 33 (48%) of 69 in the total mesorectal excision group (odds ratio 1·33, 95% CI 0·62–2·86; p=0·43). In the modified ITT analysis, there was no difference between the groups in all components of the composite outcome, and superiority was not shown for local excision over total mesorectal excision. Interpretation We failed to show superiority of local excision over total mesorectal excision, because many patients in the local excision group received a completion total mesorectal excision that probably increased morbidity and side-effects, and compromised the potential advantages of local excision. Better patient selection to avoid unnecessary completion total mesorectal excision could improve the strategy. Funding National Cancer Institute of France, Sanofi, Roche Pharma.
Purpose A pathologic complete response (pCR; ypT0N0) of a rectal tumor after neoadjuvant radiochemotherapy (RCT) is associated with an excellent prognosis. Several retrospective studies have ...investigated the effect of increasing the delay after RCT. The aim of this study was to evaluate the effect of increasing the interval between the end of RCT and surgery on the pCR rate. Methods GRECCAR6 was a phase III, multicenter, randomized, open-label, parallel-group controlled trial. Patients with cT3/T4 or Tx N+ tumors of the mid or lower rectum who had received RCT (45 to 50 Gy with fluorouracil or capecitabine) were included. Patients were randomly included in the 7-week or the 11-week (11w) group. Primary end point was the pCR rate defined as a ypT0N0 specimen (NCT01648894). Results A total of 265 patients from 24 centers were enrolled between October 2012 and February 2015. The majority of the tumors were cT3 (82%). After RCT, surgery was not performed in nine patients (3.4%) because of the occurrence of distant metastasis (n = 5) or other reasons. Two patients underwent local resection of the tumor scar. A total of 47 (18.6%) specimens were classified as ypT0 (four had invaded lymph nodes 8.5%). The primary end point (ypT0N0) was not different (7 weeks: 20 of 133, 15.0% v 11w: 23 of 132, 17.4%; P = .5983). Morbidity was significantly increased in the 11w group (44.5% v 32%; P = .0404) as a result of increased medical complications (32.8% v 19.2%; P = .0137). The 11w group had a worse quality of mesorectal resection (complete mesorectum I 78.7% v 90%; P = .0156). Conclusion Waiting 11 weeks after RCT did not increase the rate of pCR after surgical resection. A longer waiting period may be associated with higher morbidity and more difficult surgical resection.
The pathological nodal stage, determination of which requires examination of ≥ 12 lymph nodes, is one of the main prognostic factors in rectal cancer. Neoadjuvant chemoradiotherapy (CRT) may reduce ...the number of both lymph nodes retrieved and positive lymph nodes. Induction chemotherapy before CRT aimed at reducing the rate of distant metastases. However, the impact of this new treatment on number of lymph nodes retrieved and positive lymph nodes is unknown. This study was performed to evaluate the effects of neoadjuvant chemotherapy on lymph nodes in locally advanced rectal cancer treated by CRT. We retrospectively included patients with T2 – 4 Nx M0 rectal cancer and compared those receiving neoadjuvant chemotherapy plus CRT with those receiving CRT alone. From 2012 to 2019, 85 patients were treated with neoadjuvant chemotherapy + CRT and 189 with CRT alone. The number of lymph nodes retrieved (19 vs. 17, respectively,
P
= 0.434), the rate of specimens with ≥ 12 lymph nodes (92% vs. 88%, respectively,
P
= 0.397), and the median number of positive lymph nodes (1 vs. 2, respectively,
P
= 0.878) were similar between the two groups. However, the rate of pN0 was higher after neoadjuvant chemotherapy + CRT compared to CRT (75% vs. 62%, respectively,
P
= 0.030). Neoadjuvant chemotherapy before CRT for locally advanced rectal cancer did not modify the number of lymph nodes retrieved or the number of positive lymph nodes compared to CRT alone. However, it significantly increased the rate of tumors without any positive lymph nodes (ypN0).
Restoration of bowel continuity is a major goal after surgical treatment of rectal cancer. Intersphincteric resection allows sphincter preservation in low rectal cancer but may have poor functional ...results, including frequent bowel movements, urgency, and incontinence.
This study aimed to evaluate long-term functional outcome after intersphincteric resection to identify factors predictive of good continence.
Descriptive observational study.
Follow-up of surgery in tertiary care university hospital.
Eligible patients were without recurrence 1 year or more after surgery for low rectal cancer.
Intersphincteric resection.
: Bowel function was assessed with a standardized questionnaire sent to patients. Functional outcome was considered as good if the Wexner score was 10 or less. Univariable and multivariable regression analyses were used to evaluate impact of age, gender, body mass index, tumor stage, tumor location, distance of the tumor from the anal verge and from the anal ring, type of surgery, colonic pouch, height of the anastomosis, pelvic sepsis, and preoperative radiotherapy on functional outcome.
Of 125 eligible patients, 101 responded to the questionnaire. Median follow-up was 51 (range, 13-167) months. In multivariate analyses, the only independent predictors of good continence were distance of the tumor greater than 1 cm from the anal ring (OR, 5.88; 95% CI, 1.75-19.80; P = .004) and anastomoses higher than 2 cm above the anal verge (OR, 6.59; 95% CI, 1.12-38.67; P = .037).
The study is limited by its retrospective, observational design and potential bias due to possible differences between those who responded to the questionnaire and those who did not.
Patient characteristics do not appear to influence functional outcome at long-term follow-up after intersphincteric resection. The risk of fecal incontinence depends mainly on tumor level and height of the anastomosis.
Background
Magnetic resonance imaging (MRI) methods for chemoradiotherapy (CRT) response assessment of rectal cancer include posttreatment T staging (ymrT), tumor regression grading (mrTRG), volume ...reduction posttreatment, and modified RECIST measurement. We compared these methods in identifying good versus poor responders with the histopathological standards of T stage (ypT) and tumor regression grading (TRG).
Methods
A total of 86 patients underwent CRT in a prospective phase II trial for MRI-defined locally advanced rectal cancer. Two readers independently assessed MRIs for ymrT, mrTRG, volume change, and RECIST. Parameters for each case were categorized as good or poor response and analyzed against ypT and TRG by univariate logistic regression.
Results
A total of 83 patients had evaluable imaging, and 78 had final pathology (five did not undergo surgery). Of these, 34 patients had good response (ypT0-3a) and 44 had poor response (>ypT3a). Also, 27 patients had favorable pathologic TRG (predominant fibrosis) and 51 had unfavorable TRG (predominant tumor). Good mrTRG and ymr <T3b stage were both significantly (
P
= 0.001) associated with favorable pathology odds ratio OR = 16.11 (95 % confidence interval 95 % CI: 3.36–77.29) and 17.50 (95 % CI: 5.38–56.89), respectively. RECIST measurements and volume reduction of >80 % showed an OR of 3.23 (95 % CI: 1.14–9.17), 4.25 (95 % CI: 0.92–15.45), respectively, for a good ypT score (
P
= 0.028), but there was no association for histopathological TRG.
Conclusion
Favorable and unfavorable histopathology are predicted by both ymrT and mrTRG, and we recommend these parameters for post-treatment assessment of rectal cancers treated with CRT.
Preoperative radiochemotherapy and total mesorectal excision are the standard-of-care for locally advanced rectal carcinoma, but some patients could be over- or undertreated.
This study aimed to ...assess the feasibility of radiochemotherapy tailored based on the tumor response to induction chemotherapy (FOLFIRINOX) to obtain a minimum R0 resection rate of 90% in the 4 arms of the study.
This study is a multicenter randomized trial (NCT01333709).
This study was conducted at 16 French cancer specialty centers.
Two hundred six patients with locally advanced rectal carcinoma were enrolled between 2011 and 2014.
Good responders (≥75% tumor volume reduction) were randomly assigned to immediate surgery (arm A) or standard radiochemotherapy (Cap 50: 50 Gy irradiation and 1600 mg/m oral capecitabine daily) plus surgery (arm B). Poor responders were randomly assigned to Cap 50 (arm C) or intensive radiochemotherapy (Cap 60, 60 Gy irradiation, arm D) before surgery.
The primary end point was a R0 resection rate (circumferential resection margin >1 mm).
The experimental strategies were to be considered effective if at least 28 successes (R0 resection) among 31 patients in each arm of stratum I and 34 successes among 40 patients in each arm of stratum II were reported (Simon 2-stage design).
After induction treatment (good compliance), 194 patients were classified as good (n = 30, 15%) or poor (n = 164, 85%) responders who were included in arms A and B (16 and 14 patients) and arms C and D (113 and 51 patients). The trial was prematurely stopped because of low accrual in arms A and B and recruitment completion in arms C and D. Data from 133 randomly assigned patients were analyzed: 11, 19, 52, and 51 patients in arms A, B, C, and D. Good responders had smaller tumors than poor responders (23 cm vs 45 cm; p < 0.001). The surgical procedure was similar among groups. The R0 resection rates 90% CI were 100% 70-100, 100% 85-100, 83% 72-91, and 88% 77-95. Among the first 40 patients, 34 successes were reported in arms C and D (85% R0 resection rate). The circumferential resection margin ≤1 rates were 0%, 0%, 12%, and 5% in arms A, B, C, and D. The rate of transformation from positive to negative circumferential resection margin was 93%.
There was low accrual in arms A and B.
Tailoring preoperative radiochemotherapy based on the induction treatment response appears safe for poor responders and promising for good responders. Long-term clinical results are needed to confirm its efficacy. See Video Abstract at http://links.lww.com/DCR/A359.
The number and status of lymph nodes examined is crucial for tumor staging. Impact of preoperative chemoradiotherapy on lymph nodes status and survival is still controversial in rectal carcinoma. The ...aim of this study was (i) to define the impact of preoperative chemoradiotherapy on the number of both retrieved and positive lymph nodes in rectal cancer specimen, (ii) to evaluate the influence of the number of lymph nodes retrieved on survival in patients treated by preoperative chemoradiotherapy. From 1994 to 2004, 495 patients underwent rectal excision for cancer, of which 332 received long course preoperative radiotherapy. Surgery and pathologic assessment were standardized. Multivariate analysis evaluated the influence of clinical and pathologic variables on the number of both retrieved and positive lymph nodes. Kaplan-Meier method and log-rank test assessed the relation between survival and the number of lymph nodes retrieved in patients treated by preoperative chemoradiotherapy. Compared with surgery alone, preoperative chemoradiotherapy decreased both the mean number of lymph nodes retrieved (17 vs. 13; P<0.001) and the mean number of positive lymph nodes (2.3 vs. 1.2; P=0.001). Multivariate analysis confirmed the independent impact of preoperative chemoradiotherapy on retrieved and positive lymph nodes. In patients treated by preoperative chemoradiotherapy, the 5-year overall (71%) and disease-free (60%) survival was not associated with the number of lymph nodes retrieved. Although long course preoperative chemoradiotherapy decreases by 24%, the mean number of lymph nodes retrieved and by 48% the mean number of positive lymph nodes, survival was not influenced by the number of lymph nodes retrieved in irradiated rectal specimen.
Opinion statement
Since total neoadjuvant treatment achieves almost 30% pathologic complete response, organ preservation has been increasingly debated for good responders after neoadjuvant treatment ...for patients diagnosed with rectal cancer. Two organ preservation strategies are available: a
watch and wait
strategy and a local excision strategy including patients with a near clinical complete response. A major issue is the selection of patients according to the initial tumor staging or the response assessment. Despite modern imaging improvement, identifying complete response remains challenging. A better selection could be possible by radiomics analyses, exploiting numerous image features to feed data characterization algorithms. The subsequent step is to include baseline and/or pre-therapeutic MRI, PET-CT, and CT radiomics added to the patients’ clinicopathological data, inside machine learning (ML) prediction models, with predictive or prognostic purposes. These models could be further improved by the addition of new biomarkers such as circulating tumor biomarkers, molecular profiling, or pathological immune biomarkers.
Graphical Abstract
Background
Synchronous prostate cancer (PC) and rectal cancer (RC) is a rare clinical situation. While combining curative-intent management for both cancers can be challenging, available data for ...guiding the multidisciplinary strategy are lacking.
Methods
Consecutive patients undergoing rectal resection for a mid-low RC with synchronous PC treated at 9 tertiary-care centers between 2008 and 2018 were included. Management strategy and data on postoperative and long-term outcomes were retrospectively analyzed.
Results
Overall, 25 patients underwent curative-intent RC resection combined with PC management. Nine (36%), 10 (40%) and 6 (24%) patients had low-, intermediate-, and high-risk PC, respectively. Management mostly consisted of chemoradiotherapy combined in 18 patients (72%) with either TME in 12 patients or pelvic exenteration for resection of both cancers in 6 patients. Most patients underwent RC resection using a laparoscopic approach (
n
= 16, 64%). Anastomosis was performed in 18 patients (72%) of whom 13 received diverting ileostomy. The complete R0 resection rate was 96% (
n
= 24). The overall morbidity rate was 64% (
n
= 16) and 5 patients (20%) experienced severe surgical morbidity of which two died within 90 days of surgery after pelvic exenteration. Among patients with anastomosis, 2 patients (11%) experienced anastomotic leak requiring surgical management. After a median follow-up of 31.2 months, 3-year OS and RFS were 80.2% (CI 95% 58.8–92.2) and 68.6% (CI 95% 42.3–84.8), respectively.
Conclusions
This series is the largest to report that simultaneous curative-intent management of synchronous PC and RC is feasible and safe. Pelvic exenteration might be a better option when RC complete resection seems not achievable through TME.
