Adjuvant Hyperthermic Intraperitoneal Chemotherapy in Patients With Locally Advanced Colon Cancer (COLOPEC): 5-Year Results of a Randomized Multicenter Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Whether adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) might prevent peritoneal metastases after curative surgery for high-risk colon cancer is an ongoing debate. This study aimed to determine 5-year oncologic outcomes of the randomized multicenter COLOPEC trial, which included patients with clinical or pathologic T4N0-2M0 or perforated colon cancer and randomly assigned (1:1) to either adjuvant systemic chemotherapy and HIPEC (n = 100) or adjuvant systemic chemotherapy alone (n = 102). HIPEC was performed using a one-time administration of oxaliplatin (460 mg/m2, 30 minutes, 42°C, concurrent fluorouracil/leucovorin intravenously), either simultaneously (9%) or within 5-8 weeks (91%) after primary tumor resection. Outcomes were analyzed according to the intention-to-treat principle. Long-term data were available of all 202 patients included in the COLOPEC trial, with a median follow-up of 59 months (IQR, 54.5-64.5). No significant difference was found in 5-year overall survival rate between patients assigned to adjuvant HIPEC followed by systemic chemotherapy or only adjuvant systemic chemotherapy (69.6% v 70.9%, log-rank; P = .692). Five-year peritoneal metastases rates were 63.9% and 63.2% (P = .907) and 5-year disease-free survival was 55.7% and 52.3% (log-rank; P = .875), respectively. No differences in quality-of-life outcomes were found. Our findings implicate that adjuvant HIPEC should still be performed in trial setting only.

Mesenteric occlusive disease of the inferior mesenteric artery is associated with anastomotic leak after left-sided colon and rectal cancer surgery: a retrospective cohort study.

PURPOSE: Anastomotic leak (AL) is a serious complication following colorectal surgery. Atherosclerosis causes inadequate anastomotic perfusion and is suggested to be a risk factor for AL. The aim of this study was to investigate the association of mesenteric occlusive disease on preoperative computed tomography (CT) scan with AL after left-sided colon or rectal cancer surgery. METHODS: This was a retrospective, multicenter cohort study including 1273 patients that underwent left-sided or rectal cancer resection between 2009 and 2018 from three hospitals in the Netherlands. AL patients were 1:1 matched with non-leak patients and preoperative contrast-enhanced CT-scans were retrospectively analyzed for mesenteric atherosclerotic lesions. The main outcome measure was the presence of mesenteric occlusive disease on the preoperative CT-scan. RESULTS: Anastomotic leak developed in 6% of 1273 patients (N = 76). Low anterior resection and stage I-III disease were statistically significant associated with AL (p = 0.01, p = 0.04). No other statistically significant differences in patient characteristics between AL and non-leak patients were found. A clinically significant stenosis (≥ 70-100%) of the inferior mesenteric artery was statistically significant more frequent present in AL patients, compared to non-leak patients (p < 0.01). No statistically significant differences in the presence of mesenteric occlusive disease of the celiac artery and superior mesenteric artery between AL patients and non-leak patients were found. CONCLUSION: Mesenteric occlusive disease of the IMA on preoperative CT-scan is associated with AL after left-sided colon or rectal resection for cancer. Preoperative identification of high-risk patients with a preoperative CT-scan of the mesenteric vasculature might be useful to reduce the risk of AL.

Treatment of recurrence after transanal endoscopic microsurgery (TEM) for T1 rectal cancer.

PURPOSE: The aim of this study was to evaluate the management and outcome of local recurrences after transanal endoscopic microsurgery for T1 rectal cancer. METHODS: Consecutive patients who underwent transanal endoscopic microsurgery for pT1 rectal cancer at a Dutch referral center (IJsselland Hospital) were registered in a prospective database. Follow-up was according to Dutch guidelines on rectal cancer, with additional rigid rectoscopy and endorectal ultrasound examinations every 3 months for the first 2 years, and every 6 months thereafter. Annual MRI of the lesser pelvis was added during the last 2 years of the study. Patients with local recurrence during follow-up were selected for individual analysis of outcome. RESULTS: Of a total of 88 patients who underwent transanal endoscopic microsurgery for pT1 rectal cancer, 18 patients (20.5%) had a local recurrence. Median time to local recurrence was 10 (range, 4-50) months. Median age at diagnosis of recurrence was 74 (range, 56-84) years. Of the 18 patients, 2 did not undergo further surgery because of concomitant metastatic disease, and 16 underwent salvage surgery, without need for multivisceral resections. No postoperative mortality was observed. In 15 patients (94%), a microscopically negative excision margin was obtained; in 1 patient, the excision margin was microscopically positive. Median follow-up after salvage surgery was 20 (range, 2-112) months. One patient had a local renewal of recurrence, and 7 patients (39%) had distant metastases. At 3 years, overall survival was 31%; cancer-related survival was 58%. CONCLUSIONS: Recurrent disease after transanal endoscopic microsurgery for T1 rectal cancer is a major problem. Although salvage surgery for achieving local control is feasible in most patients, survival is limited, mainly because of distant metastases. Tailoring selection of T1 rectal cancers and exploring possible adjuvant treatment strategies following salvage procedures should be the next steps toward improving survival.

Preoperative radiotherapy has no value for patients with T2-3, N0 adenocarcinomas of the rectum.

BACKGROUND: Treatment of rectal cancer with preoperative radiotherapy followed by total mesorectal excision is nowadays the standard treatment. It reduces local recurrences and improves overall survival. However, in patients with T2-3, N0 rectal cancer, the role of preoperative radiotherapy remains controversial. The aim of this study was to review the benefit of radiotherapy in T2 and T3, N0 rectal cancer patients. METHODS: Between 1996 and 2003, 103 patients with T2-3, N0 rectal cancer were identified in our prospective database. This study evaluated time to local recurrence, distant metastases and overall survival. RESULTS: Median follow-up was 4.3 years. The 5-year local control rate was 94%. The 5-year overall survival was 65%. The 5-year disease-free survival rate was 82%. Preoperative radiotherapy did not show any statistical differences. Abdominal perineal resection and T3 tumors negatively influenced overall survival (p = 0.02). Advanced age was of significant importance in overall survival. CONCLUSIONS: Preoperative radiotherapy does not seem to be of significant importance in patients with T2-3, N0 rectal cancer regarding local recurrence and survival. Since preoperative radiotherapy is associated with short- and long-term morbidity, patients with T2-3, N0 tumors should be identified and treated with surgery alone.

Total mesorectal excision for rectal cancer in an unselected population: quality assessment in a low volume center.

OBJECTIVE: The aim of this study was to review the results and long-term outcome after total mesorectal excision (TME) for adenocarcinoma of the rectum in an unselected population in a community teaching hospital. MATERIALS AND METHODS: Between 1996 and 2003, 210 patients with rectal cancer were identified in our prospective database, containing patient characteristics, radiotherapy plans, operation notes, histopathological reports, and follow-up details. An evaluation of prognostic factors for local recurrence, distant metastases, and overall survival was performed. RESULTS: The mean age at diagnosis was 69 years (range 40-91 years). A total of 145 patients were treated by anterior rectal resection; 65 patients had to undergo an abdominoperineal resection (APR). Anastomotic leakage rate was 5%. Postoperative mortality was 3%. After a median follow-up of 3.6 years, the local recurrence-free rate in patients with microscopically complete resections was 91%. The 5-year overall survival rate was 58%. An increased serum carcinoembryonic antigen, an APR, positive lymph nodes, and an incomplete resection all significantly influenced the 5-year overall survival and local recurrence rate. In a multivariate analysis, age was the most important prognostic factor for overall survival. CONCLUSIONS: Patients with rectal cancer can safely be treated with TME in a community teaching hospital and leads to a good overall survival and an excellent local control. In patients aged above 80, treatment-related mortality is an important competitive risk factor, which obscures the positive effect of modern rectal cancer treatment.

Reirradiation, surgery and IORT for recurrent rectal cancer in previously irradiated patients.

A total of 11 patients with recurrent rectal cancer who had been previously irradiated were treated with preoperative reirradiation (median dose 30Gy), surgery and IORT. This treatment was related with high morbidity, a short pain-free survival (5 months) and poor local control (27% after 3 years), although some patients have long-term distant control and survival.

Management of locally advanced primary and recurrent rectal cancer.

Treatment for patients with locally advanced and recurrent rectal cancer differs significantly from patients with rectal cancer restricted to the mesorectum. Adequate preoperative imaging of the pelvis is therefore important to identify those patients who are candidates for multimodality treatment, including preoperative chemoradiation protocols, intraoperative radiotherapy, and extended surgical resections. Much effort should be made to select patients with these advanced tumors for treatment in specialized referral centers. This has been shown to reduce morbidity and mortality and improve long-term survival rates. In this article, we review the best treatment options for patients with locally advanced and recurrent rectal cancer. We also emphasize the necessity of a multidisciplinary team, including a radiologist, radiation oncologist, urologist, surgical oncologist, plastic surgeon, and gynecologist in the diagnosis and treatment of patients with these pelvic tumors.

Value of intraoperative radiotherapy in locally advanced rectal cancer.

PURPOSE: This study was designed to analyze the results of a multimodality treatment using preoperative radiotherapy, followed by surgery and intraoperative radiotherapy in patients with primary locally advanced rectal cancer. METHODS: Between 1987 and 2002, 123 patients with initial unresectable and locally advanced rectal cancer were identified in our prospective database, containing patient characteristics, radiotherapy plans, operation notes, histopathologic reports, and follow-up details. An evaluation of prognostic factors for local recurrence, distant metastases, and overall survival was performed. RESULTS: All patients were treated preoperatively with a median dose of 50 Gy radiotherapy. Surgery was performed six to ten weeks after radiotherapy. Twenty-seven patients were treated with intraoperative radiotherapy because margins were incomplete or

Salvage abdominoperineal resection and perineal wound healing in local recurrent or persistent anal cancer.

The primary treatment for anal cancer is chemoradiation (CRT). Failures after CRT are potentially curable with an abdominoperineal resection (APR). A major problem of surgery in the anal area is poor healing of the perineal wound. Between 1985 and 2000, 129 patients treated for anal cancer were retrospectively reviewed. Of the 24 patients with local failure, 18 patients were treated with an APR. The aim of this study was to review the results and long-term outcome after salvage APR, with special emphasis on perineal wound healing. Mean age at diagnosis was 59 (range: 41-83) years. After a median of 16 months, only 2 patients developed a local recurrence. The 5-year overall survival was 30%. In 11 patients the perineal wound was closed primarily, in 3 patients the perineal wound was left open, and in 4 patients a vertical rectus abdominus musculocutaneous (VRAM) flap was used. Perineal wound breakdown occurred in 5 of the 14 patients (36%) not treated with primary muscle reconstruction. In all patients treated with a VRAM flap the perineal wound healed primarily. In the present study salvage APR in recurrent or persistent anal cancer results in good local control and 5-year overall survival of 30%. When performing an APR a VRAM flap reconstruction should be considered to prevent disabling perineal wound complications.

Preoperative radiotherapy improves outcome in recurrent rectal cancer.

PURPOSE: When local recurrent rectal cancer is diagnosed without signs of metastases, a potentially curative resection can be performed. This study was designed to compare the results of preoperative radiotherapy followed by surgery with surgery only. METHODS: Between 1985 and 2003, 117 patients with recurrent rectal cancer were prospectively entered in our database. Ninety-two patients were suitable for resection with curative intent. Preoperative radiation with a median dosage of 50 Gy was performed in 59 patients; 33 patients did not receive preoperative radiotherapy. The median age of the patients was respectively 66 and 62 years. RESULTS: The median follow-up of patients alive for the total group was 16 (range, 4-156) months. Tumor characteristics were comparable between the two groups. Complete resections were performed in 64 percent of the patients who received preoperative radiation and 45 percent of the nonirradiated patients. A complete response after radiotherapy was found in 10 percent of the preoperative irradiated patients (n = 6). There were no differences in morbidity and reintervention rate between the two groups. Local control after preoperative radiotherapy was statistically significantly higher after three and five years (P = 0.036). Overall survival and metastases-free survival were not different in both groups. Complete response to preoperative radiotherapy was predictive for an improved survival. CONCLUSIONS: Preoperative radiotherapy for recurrent rectal cancer results in a higher number of complete resections and an improved local control compared with patients treated without radiotherapy. Preoperative radiotherapy should be standard treatment for patients with recurrent rectal cancer.