Gerald W Prager, Julien Taieb, Marwan Fakih, Fortunato Ciardiello, Eric Van Cutsem, Elena Elez, Felipe M Cruz, Lucjan Wyrwicz, Daniil Stroyakovskiy, Zsuzsanna Pápai, Pierre-Guillaume Poureau, Gabor Liposits, Chiara Cremolini, Igor Bondarenko, Dominik P Modest, Karim A Benhadji, Nadia Amellal, Catherine Leger, Loïck Vidot, Josep Tabernero, SUNLIGHT Investigators
Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer.
N Engl J Med. 2023 May 4;388(18):1657-1667. doi: 10.1056/NEJMoa2214963.
Abstract/Text
BACKGROUND: In a previous phase 3 trial, treatment with trifluridine-tipiracil (FTD-TPI) prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase 2 trials suggest that treatment with FTD-TPI in addition to bevacizumab has the potential to extend survival.
METHODS: We randomly assigned, in a 1:1 ratio, adult patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer to receive FTD-TPI plus bevacizumab (combination group) or FTD-TPI alone (FTD-TPI group). The primary end point was overall survival. Secondary end points were progression-free survival and safety, including the time to worsening of the Eastern Cooperative Oncology Group (ECOG) performance-status score from 0 or 1 to 2 or more (on a scale from 0 to 5, with higher scores indicating greater disability).
RESULTS: A total of 246 patients were assigned to each group. The median overall survival was 10.8 months in the combination group and 7.5 months in the FTD-TPI group (hazard ratio for death, 0.61; 95% confidence interval [CI], 0.49 to 0.77; P<0.001). The median progression-free survival was 5.6 months in the combination group and 2.4 months in the FTD-TPI group (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.54; P<0.001). The most common adverse events in both groups were neutropenia, nausea, and anemia. No treatment-related deaths were reported. The median time to worsening of the ECOG performance-status score from 0 or 1 to 2 or more was 9.3 months in the combination group and 6.3 months in the FTD-TPI group (hazard ratio, 0.54; 95% CI, 0.43 to 0.67).
CONCLUSIONS: Among patients with refractory metastatic colorectal cancer, treatment with FTD-TPI plus bevacizumab resulted in longer overall survival than FTD-TPI alone. (Funded by Servier and Taiho Oncology; SUNLIGHT ClinicalTrials.gov number, NCT04737187; EudraCT number, 2020-001976-14.).
Copyright © 2023 Massachusetts Medical Society.
Andrew G Renehan, Matthias Egger, Mark P Saunders, Sarah T O'Dwyer
Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials.
BMJ. 2002 Apr 6;324(7341):813.
Abstract/Text
OBJECTIVE: To review the evidence from clinical trials of follow up of patients after curative resection for colorectal cancer.
DESIGN: Systematic review and meta-analysis of randomised controlled trials of intensive compared with control follow up.
MAIN OUTCOME MEASURES: All cause mortality at five years (primary outcome). Rates of recurrence of intraluminal, local, and metastatic disease and metachronous (second colorectal primary) cancers (secondary outcomes).
RESULTS: Five trials, which included 1342 patients, met the inclusion criteria. Intensive follow up was associated with a reduction in all cause mortality (combined risk ratio 0.81, 95% confidence interval 0.70 to 0.94, P=0.007). The effect was most pronounced in the four extramural detection trials that used computed tomography and frequent measurements of serum carcinoembryonic antigen (risk ratio 0.73, 0.60 to 0.89, P=0.002). Intensive follow up was associated with significantly earlier detection of all recurrences (difference in means 8.5 months, 7.6 to 9.4 months, P<0.001) and an increased detection rate for isolated local recurrences (risk ratio 1.61, 1.12 to 2.32, P=0.011).
CONCLUSIONS: Intensive follow up after curative resection for colorectal cancer improves survival. Large trials are required to identify which components of intensive follow up are most beneficial.
Alvaro Figueredo, R Bryan Rumble, Jean Maroun, Craig C Earle, Bernard Cummings, Robin McLeod, Lisa Zuraw, Caroline Zwaal, Gastrointestinal Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence-based Care
Follow-up of patients with curatively resected colorectal cancer: a practice guideline.
BMC Cancer. 2003 Oct 6;3:26. doi: 10.1186/1471-2407-3-26. Epub 2003 Oct 6.
Abstract/Text
BACKGROUND: A systematic review was conducted to evaluate the literature regarding the impact of follow-up on colorectal cancer patient survival and, in a second phase, recommendations were developed.
METHODS: The MEDLINE, CANCERLIT, and Cochrane Library databases, and abstracts published in the 1997 to 2002 proceedings of the annual meeting of the American Society of Clinical Oncology were systematically searched for evidence. Study selection was limited to randomized trials and meta-analyses that examined different programs of follow-up after curative resection of colorectal cancer where five-year overall survival was reported. External review by Ontario practitioners was obtained through a mailed survey. Final approval of the practice guideline report was obtained from the Practice Guidelines Coordinating Committee.
RESULTS: Six randomized trials and two published meta-analyses of follow-up were obtained. Of six randomized trials comparing one follow-up program to a more intense program, only two individual trials detected a statistically significant survival benefit favouring the more intense follow-up program. Pooling of all six randomized trials demonstrated a significant improvement in survival favouring more intense follow-up (Relative Risk Ratio 0.80 (95%CI, 0.70 to 0.91; p = 0.0008). Although the rate of recurrence was similar in both of the follow-up groups compared, asymptomatic recurrences and re-operations for cure of recurrences were more common in patients with more intensive follow-up. Trials including CEA monitoring and liver imaging also had significant results, whereas trials not including these tests did not.
CONCLUSION: Follow-up programs for patients with curatively resected colorectal cancer do improve survival. These follow-up programs include frequent visits and performance of blood CEA, chest x-rays, liver imaging and colonoscopy, however, it is not clear which tests or frequency of visits is optimal. There is a suggestion that improved survival is due to diagnosis of recurrence at an earlier, asymptomatic stage which allows for more curative resection of recurrence. Based on this evidence and consideration of the biology of colorectal cancer and present practices, a guideline was developed. Patients should be made aware of the risk of disease recurrence or second bowel cancer, the potential benefits of follow-up and the uncertainties requiring further clinical trials. For patients at high-risk of recurrence (stages IIb and III) clinical assessment is recommended when symptoms occur or at least every 6 months the first 3 years and yearly for at least 5 years. At the time of those visits, patients may have blood CEA, chest x-ray and liver imaging. For patients at lower risk of recurrence (stages I and Ia) or those with co-morbidities impairing future surgery, only visits yearly or when symptoms occur. All patients should have a colonoscopy before or within 6 months of initial surgery, and repeated yearly if villous or tubular adenomas >1 cm are found; otherwise repeat every 3 to 5 years. All patients having recurrences should be assessed by a multidisciplinary team in a cancer centre.
Joe J Tjandra, Miranda K Y Chan
Follow-up after curative resection of colorectal cancer: a meta-analysis.
Dis Colon Rectum. 2007 Nov;50(11):1783-99. doi: 10.1007/s10350-007-9030-5.
Abstract/Text
PURPOSE: This is a systematic review to evaluate the impact of various follow-up intensities and strategies on the outcome of patients after curative surgery for colorectal cancer.
METHODS: All randomized trials up to January 2007, comparing different follow-up intensities and strategies, were retrieved. Meta-analysis was performed by using the Forest plot review.
RESULTS: Eight randomized, clinical trials with 2,923 patients with colorectal cancer undergoing curative resection were reviewed. There was a significant reduction in overall mortality in patients having intensive follow-up (intensive vs. less intensive follow-up: 21.8 vs. 25.7 percent; P = 0.01). Regular surveillance with serum carcinoembryonic antigen (P = 0.0002) and colonoscopy (P = 0.04) demonstrated a significant impact on overall mortality. However, cancer-related mortality did not show any significant difference. There was no significant difference in all-site recurrence and in local or distant metastasis. Detection of isolated local and hepatic recurrences was similar. Intensive follow-up detected asymptomatic recurrence more frequently (18.9 vs. 6.3 percent; P < 0.00001) and 5.91 months earlier than less intensive follow-up protocol; these were demonstrated with all investigation strategies used. Intensive surveillance program detected recurrences that were significantly more amenable to surgical reresection (10.7 vs. 5.7 percent; P = 0.0002). The chance of curative reresection were significantly better with more intensive follow-up (24.3 vs. 9.9 percent; P = 0.0001), independent of the investigation strategies used.
CONCLUSIONS: Intensive follow-up after curative resection of colorectal cancer improved overall survival and reresection rate for recurrent disease. However, the cancer-related mortality was not improved and the survival benefit was not related to earlier detection and treatment of recurrent disease.
M Jeffery, B E Hickey, P N Hider
Follow-up strategies for patients treated for non-metastatic colorectal cancer.
Cochrane Database Syst Rev. 2007 Jan 24;(1):CD002200. doi: 10.1002/14651858.CD002200.pub2. Epub 2007 Jan 24.
Abstract/Text
BACKGROUND: It is common clinical practice to follow patients with colorectal cancer (CRC) for several years following their definitive surgery and/or adjuvant therapy. Despite this widespread practice there is considerable controversy about how often patients should be seen, what tests should be performed and whether these varying strategies have any significant impact on patient outcomes.
OBJECTIVES: To review the available evidence concerning the benefits of intensive follow up of colorectal cancer patients with respect to survival. Secondary endpoints include time to diagnosis of recurrence, quality of life and the harms and costs of surveillance and investigations.
SEARCH STRATEGY: Relevant trials were identified by electronic searches of MEDLINE, EMBASE, CINAHL, CANCERLIT, Cochrane Controlled Trials Register, Science Citation Index, conference proceedings, trial registers, reference lists and contact with experts in the field.
SELECTION CRITERIA: Only randomised controlled trials comparing different follow-up strategies for patients with non-metastatic CRC treated with curative intent were included.
DATA COLLECTION AND ANALYSIS: Trial eligibility and methodological quality were assessed independently by the three authors.
MAIN RESULTS: Eight studies were included in this update of the review. There was evidence that an overall survival benefit at five years exists for patients undergoing more intensive follow up OR was 0.73 (95% CI 0.59 to 0.91); and RD -0.06 (95% CI -0.11 to -0.02). The absolute number of recurrences was similar; OR was 0.91 (95% CI 0.75 to 1.10); and RD -0.02 (95% CI -0.06 to 0.02) and although the weighted mean difference for the time to recurrence was significantly reduced by -6.75 (95% CI -11.06 to -2.44) there was significant heterogeneity between the studies. Analyses demonstrated a mortality benefit for performing more tests versus fewer tests OR was 0.64 (95% CI 0.49 to 0.85), and RD -0.09 (95%CI -0.14 to -0.03) and liver imaging versus no liver imaging OR was 0.64 (95% CI 0.49 to 0.85), and RD -0.09 (95%CI -0.14 to -0.03). There were significantly more curative surgical procedures attempted in the intensively followed arm: OR 2.41(95% CI 1.63 to 3.54), RD 0.06 (95%CI 0.04 to 0.09). No useful data on quality of life, harms or cost-effectiveness were available for further analysis.
AUTHORS' CONCLUSIONS: The results of our review suggest that there is an overall survival benefit for intensifying the follow up of patients after curative surgery for colorectal cancer. Because of the wide variation in the follow-up programmes used in the included studies it is not possible to infer from the data the best combination and frequency of clinic (or family practice) visits, blood tests, endoscopic procedures and radiological investigations to maximise the outcomes for these patients. Nor is it possible to estimate the potential harms or costs of intensifying follow up for these patients in order to adopt a cost-effective approach in this clinical area. Large clinical trials underway or about to commence are likely to contribute valuable further information to clarify these areas of clinical uncertainty.
Hideki Ueno, Hidetaka Mochizuki, Yojiro Hashiguchi, Hideyuki Shimazaki, Shinsuke Aida, Kazuo Hase, Susumu Matsukuma, Tadao Kanai, Hiroyuki Kurihara, Kotaro Ozawa, Kazuyoshi Yoshimura, Shinya Bekku
Risk factors for an adverse outcome in early invasive colorectal carcinoma.
Gastroenterology. 2004 Aug;127(2):385-94.
Abstract/Text
BACKGROUND & AIMS: Various histologic findings exist for managing patients with malignant polyps. Our goal was to determine the criteria for a conservative approach to patients with locally excised early invasive carcinoma.
METHODS: In 292 early invasive tumors (local resection followed by laparotomy [80 tumors, group A], local resection only [41 tumors, group B], and primarily laparotomy [171 tumors, group C], potential parameters for nodal involvement were analyzed. The status of the endoscopic resection margin also was examined for the risk for intramural residual tumor.
RESULTS: Unfavorable tumor grade, definite vascular invasion, and tumor budding were the combination of qualitative factors that most effectively discriminated the risk for nodal involvement in patients in groups A-C. The nodal involvement rate was 0.7%, 20.7%, and 36.4% in the no-risk, single-risk, and multiple-risks group, respectively. Thirty-two and 9 patients from group B were assigned to the no-risk and one-risk group, respectively; extramural recurrence occurred in 2 patients with risk factors. Considering quantitative risk parameters for submucosal invasion (i.e., width > or =4000 microm or depth > or =2000 microm), nodal involvement (including micrometastases) was not observed in the redefined no-risk group that accounted for about 25% of the patients from groups A and C. An insufficiency of endoscopic resection could be evaluated most precisely based on the coagulation-involving tumor, rather than the 1-mm rule for the resection margin.
CONCLUSIONS: Provided that the criterion of sufficient excision is satisfied, the absence of an unfavorable tumor grade, vascular invasion, tumor budding, and extensive submucosal invasion would be the strict criteria for a wait-and-see policy.
Kazuaki Kitajima, Takahiro Fujimori, Shigehiko Fujii, Jun Takeda, Yasuo Ohkura, Hitoshi Kawamata, Toshihide Kumamoto, Shingo Ishiguro, Yo Kato, Tadakazu Shimoda, Akinori Iwashita, Yoichi Ajioka, Hidenobu Watanabe, Toshiaki Watanabe, Tetsuichiro Muto, Ko Nagasako
Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study.
J Gastroenterol. 2004 Jun;39(6):534-43. doi: 10.1007/s00535-004-1339-4.
Abstract/Text
BACKGROUND: Depth of submucosal invasion (SM depth) in submucosal invasive colorectal carcinoma (SICC) is considered an important predictive factor for lymph node metastasis. However, no nationwide reports have clarified the relationship between SM depth and rate of lymph node metastasis. Our aim was to investigate the correlations between lymph node metastasis and SM depth in SICC.
METHODS: SM depth was measured for 865 SICCs that were surgically resected at six institutions throughout Japan. For pedunculated SICC, the level 2 line according to Haggitt's classification was used as baseline and the SM depth was measured from this baseline to the deepest portion in the submucosa. When the deepest portion of invasion was limited to above the baseline, the case was defined as a head invasion. For nonpedunculated SICC, when the muscularis mucosae could be identified, the muscularis mucosae was used as baseline and the vertical distance from this line to the deepest portion of invasion represented SM depth. When the muscularis mucosae could not be identified due to carcinomatous invasion, the superficial aspect of the SICC was used as baseline, and the vertical distance from this line to the deepest portion was determined.
RESULTS: For pedunculated SICC, rate of lymph node metastasis was 0% in head invasion cases and stalk invasion cases with SM depth <3000 micro m if lymphatic invasion was negative. For nonpedunculated SICC, rate of lymph node metastasis was also 0% if SM depth was <1000 micro m.
CONCLUSIONS: These results clarified rates of lymph node metastasis in SICC according to SM depth, and may contribute to defining therapeutic strategies for SICC.
Al B Benson, Deborah Schrag, Mark R Somerfield, Alfred M Cohen, Alvaro T Figueredo, Patrick J Flynn, Monika K Krzyzanowska, Jean Maroun, Pamela McAllister, Eric Van Cutsem, Melissa Brouwers, Manya Charette, Daniel G Haller
American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer.
J Clin Oncol. 2004 Aug 15;22(16):3408-19. doi: 10.1200/JCO.2004.05.063. Epub 2004 Jun 15.
Abstract/Text
PURPOSE: To address whether all medically fit patients with curatively resected stage II colon cancer should be offered adjuvant chemotherapy as part of routine clinical practice, to identify patients with poor prognosis characteristics, and to describe strategies for oncologists to use to discuss adjuvant chemotherapy in practice.
METHODS: An American Society of Clinical Oncology Panel, in collaboration with the Cancer Care Ontario Practice Guideline Initiative, reviewed pertinent information from the literature through May 2003.
RESULTS: A literature-based meta-analysis found no evidence of a statistically significant survival benefit of adjuvant chemotherapy for stage II patients. Recommendations The routine use of adjuvant chemotherapy for medically fit patients with stage II colon cancer is not recommended. However, there are populations of patients with stage II disease that could be considered for adjuvant therapy, including patients with inadequately sampled nodes, T4 lesions, perforation, or poorly differentiated histology.
CONCLUSION: Direct evidence from randomized controlled trials does not support the routine use of adjuvant chemotherapy for patients with stage II colon cancer. Patients and oncologists who accept the relative benefit in stage III disease as adequate indirect evidence of benefit for stage II disease are justified in considering the use of adjuvant chemotherapy, particularly for those patients with high-risk stage II disease. The ultimate clinical decision should be based on discussions with the patient about the nature of the evidence supporting treatment, the anticipated morbidity of treatment, the presence of high-risk prognostic features on individual prognosis, and patient preferences. Patients with stage II disease should be encouraged to participate in randomized trials.
E J D Van Cutsem, J Oliveira, ESMO Guidelines Working Group
Colon cancer: ESMO clinical recommendations for diagnosis, adjuvant treatment and follow-up.
Ann Oncol. 2008 May;19 Suppl 2:ii29-30. doi: 10.1093/annonc/mdn077.
Abstract/Text
P H Sugarbaker
Peritonectomy procedures.
Ann Surg. 1995 Jan;221(1):29-42.
Abstract/Text
OBJECTIVE: New surgical procedures designed to assist in the treatment of peritoneal surface malignancy were sought.
BACKGROUND: Decisions regarding the treatment of cancer depend on the anatomic location of the malignancy and the biologic aggressiveness of the disease. Some patients may have isolated intra-abdominal seeding of malignancy of limited extent or of low biologic grade. In the past, these clinical situations have been regarded as lethal.
METHODS: The cytoreductive approach may require six peritonectomy procedures to resect or strip cancer from all intra-abdominal surfaces.
RESULTS: These are greater omentectomy-splenectomy; left upper quadrant peritonectomy; right upper quadrant peritonectomy; lesser omentectomy-cholecystectomy with stripping of the omental bursa; pelvic peritonectomy with sleeve resection of the sigmoid colon; and antrectomy.
CONCLUSIONS: Peritonectomy procedures and preparation of the abdomen for early postoperative intraperitoneal chemotherapy were described. The author has used the cytoreductive approach to achieve long-term, disease-free survival in selected patients with peritoneal carcinomatosis, peritoneal sarcomatosis or mesothelioma.
S R Pestieau, P H Sugarbaker
Treatment of primary colon cancer with peritoneal carcinomatosis: comparison of concomitant vs. delayed management.
Dis Colon Rectum. 2000 Oct;43(10):1341-6; discussion 1347-8.
Abstract/Text
PURPOSE: The initial dissemination of colon cancer occurs through three routes: the lymphatics, the portal blood, and the peritoneal surfaces. Although lymphatic and hematogenous metastases indicate an aggressive disease process, it is possible that dissemination to peritoneal surfaces may be only superficial contamination of the parietal and visceral peritoneum that may be treatable for cure. Unfortunately, surgery may have an adverse impact on peritoneal surface dissemination. Surgical interventions may convert a superficial process into an invasive condition with a greatly reduced prognosis. This study was conducted to test this hypothesis by the use of data prospectively recorded from patients treated for peritoneal carcinomatosis concomitant with resection of the primary colon cancer or treated for carcinomatosis after disease recurrence prompted referral.
METHODS: Our first group of patients had definitive treatment of carcinomatosis simultaneous with resection of the primary colon cancer. They had cytoreductive surgery including peritonectomy procedures followed by heated intraoperative intraperitoneal chemotherapy with mitomycin C plus early postoperative intraperitoneal 5-fluorouracil. The comparison group was treated with a colon resection at an outside hospital and then later referred to us with progressive disease for treatment. The major difference between the groups is the timing of the definitive treatment of carcinomatosis. These patients were also studied by use of the completeness of the cytoreduction score and the peritoneal cancer index as prognostic indicators. Survival was the end point for all the analysis.
RESULTS: Of 104 patients with peritoneal carcinomatosis from colon or rectal adenocarcinoma, five patients (4.8 percent) had definitive treatment of the peritoneal surface spread of the cancer concomitant with resection of the primary lesion. Median survival for these patients has not been reached and their five-year survival rate is 100 percent. The remainder of the patients (n = 99) were referred for local and regional recurrence after their primary cancer had been removed and there was progression of carcinomatosis. Forty-four patients (42.3 percent) had a complete cytoreduction resulting in a 24-month median survival and a 30 percent five-year survival (P < 0.0001). The other 55 patients (52.9 percent) had an incomplete cytoreduction resulting in a 12-month median survival and a 0 percent five-year survival (P < 0.0001). Patients with a peritoneal cancer index of 10 or less had a 48-month median survival and a 50 percent five-year survival rate. Patients with a peritoneal cancer index between 11 and 20 had a 24-month median survival and a 20 percent five-year survival rate (P < 0.0001). Patients with a peritoneal cancer index of more than 20 had a 12-month median survival and a 0 percent five-year survival (P < 0.0001).
CONCLUSIONS: In patients with peritoneal seeding occurring at the time of resection of the primary malignancy, peritonectomy procedures and perioperative intraperitoneal chemotherapy should be performed concomitantly. By use of a quantitative scoring system, the mass of cancer present in the abdomen and pelvis at the time of treatment of carcinomatosis correlated directly with survival. Aggressive treatment of patients with peritoneal carcinomatosis requires consideration in the management of colorectal cancer.
Hirotoshi Kobayashi, Kenjiro Kotake, Kenichi Sugihara
Outcomes of surgery without HIPEC for synchronous peritoneal metastasis from colorectal cancer: data from a multi-center registry.
Int J Clin Oncol. 2014 Feb;19(1):98-105. doi: 10.1007/s10147-012-0505-6. Epub 2012 Dec 13.
Abstract/Text
BACKGROUND: Preoperative detection of small peritoneal metastases is difficult, and a convenient method is required to decide the nature of procedures subsequent to initial exploratory surgery. The aim of this study was to validate the Japanese classification of peritoneal metastasis from colorectal cancer.
METHODS: This retrospective study analyzes data from a multi-center registry. Factors affecting the extent of peritoneal metastasis, macroscopic radical resection and prognosis were analyzed using data from patients with colorectal cancer and synchronous peritoneal metastasis. Peritoneal metastasis was classified depending on extent into three groups (P1-P3).
RESULTS: Among 60,176 patients with colorectal surgery, 3,075 (5.1 %) had synchronous peritoneal metastasis. Tumor location on the right side (P < 0.0001), histological grade (P = 0.0014) and distant metastasis (P < 0.0001) were associated with the extent of peritoneal metastasis. Gender (P = 0.041), lymph node metastasis (P < 0.0001), distant metastasis (P < 0.0001), extent of peritoneal metastasis according to the present classification (P < 0.0001) and the period when the patient underwent the operation (operative period; P < 0.0001) were independently associated with macroscopic radical resection. Cox proportional hazards model disclosed that gender (P = 0.0046), tumor location (P = 0.032), age (P = 0.048), histological grade (P < 0.0001), lymph node metastasis (P < 0.0001), distant metastasis (P < 0.0001), extent of peritoneal metastasis (P < 0.0001), and macroscopic radical resection (P < 0.0001) were independent prognostic factors.
CONCLUSIONS: Macroscopic radical resection was an independent prognostic factor even without hyperthermic intraperitoneal chemotherapy. The referral of patients without distant metastasis to centers with experienced peritoneal surgeons might be a potential option if the peritoneal metastasis is unresectable in general hospitals.
Hirotoshi Kobayashi, Kenjiro Kotake, Kimihiko Funahashi, Kazuo Hase, Koichi Hirata, Tsuneo Iiai, Shingo Kameoka, Yukihide Kanemitsu, Koutarou Maeda, Akihiko Murata, Masayuki Ohue, Kazuo Shirouzu, Keiichi Takahashi, Toshiaki Watanabe, Hideaki Yano, Toshimasa Yatsuoka, Yojiro Hashiguchi, Kenichi Sugihara, Study Group for Peritoneal Metastasis from Colorectal Cancer by the Japanese Society for Cancer of the Colon and Rectum
Clinical benefit of surgery for stage IV colorectal cancer with synchronous peritoneal metastasis.
J Gastroenterol. 2014 Apr;49(4):646-54. doi: 10.1007/s00535-013-0820-3. Epub 2013 Jun 24.
Abstract/Text
BACKGROUND: Peritoneal metastasis is well-known as a poor prognostic factor in patients with colorectal cancer. It is important to improve the prognosis of patients with colorectal cancer and synchronous peritoneal metastasis. This study aimed to clarify the factors affecting R0 resection and the prognosis of colorectal cancer patients with synchronous peritoneal metastasis.
METHODS: We investigated the data of patients with stage IV colorectal cancer between 1991 and 2007 in 16 hospitals that were members of the Japanese Society for Cancer of the Colon and Rectum.
RESULTS: Of the 564 colorectal cancer patients with synchronous peritoneal metastases, 341 also had hematogenous metastases. The 5-year overall survival rates in patients with and without R0 resection were 32.4 and 4.7 %, respectively. A Cox proportional hazards model showed that histologic type of poorly differentiated adenocarcinoma, regional lymph node metastasis, liver metastasis, chemotherapy after surgery, R0 resection, the Japanese classification of peritoneal metastasis, and the size of peritoneal metastases were independent prognostic factors. Of the 564 patients, 28.4 % had R0 resection. The Japanese classification of peritoneal metastasis (P1-P2, p = 0.0024) and absence of hematogenous metastases (p < 0.0001) were associated with R0 resection.
CONCLUSIONS: P1-P2 peritoneal metastasis and the absence of hematogenous metastasis were the most favorable factors benefiting from synchronous resection of peritoneal metastasis. In addition, chemotherapy after surgery was essential.
H J Wanebo, R J Koness, M P Vezeridis, S I Cohen, D E Wrobleski
Pelvic resection of recurrent rectal cancer.
Ann Surg. 1994 Oct;220(4):586-95; discussion 595-7.
Abstract/Text
OBJECTIVE: The authors describe their experience with pelvic resection of recurrent rectal cancer with emphasis on patient selection for curative intent based on known tumor risk factors.
SUMMARY BACKGROUND DATA: Pelvic recurrence is a formidable problem in 30% of patients who have undergone a curative resection of primary rectal cancer. Although radiation can reduce the development of local recurrence and can provide palliation to many patients with localized disease, it is not curative. The authors and others have used the technique of abdominal sacral resection (ABSR) with or without pelvic exenteration to resect pelvic recurrence and its musculoskeletal extensions in selected patients with satisfactory long-term survival.
METHODS: The technique of ABSR with or without pelvic exenteration or resection of pelvic viscera, which the authors have described previously, was used in 53 patients with recurrent rectal cancer--47 patients for curative intent and 6 for palliation. Previous surgeries were abdominal perineal resections (APRs) in 26 patients, anterior resections in 19 patients, and other procedures in 2 patients; original primary Dukes' stage was B in 52% and C in 48%. Almost all patients had been irradiated previously, generally in the 4000 to 5900 cGy range. Preoperative carcinoembryonic antigen (CEA) levels (before ABSR) were elevated (> 5 ng/mL) in 54%.
RESULTS: Postoperative morbidity was encountered in most patients. Mortality was 8.5% in the curative group. Long-term survival for 4 years was achieved in 14 of 43 patients (33%), and 10 patients were alive with an acceptable quality of life after 5 years. Patients who had previous anterior resections or whose preoperative CEA levels were less than 10 ng/mL had a survival rate of approximately 45%, whereas patients with previous APRs and preoperative CEA levels greater than 10 ng/mL had a survival rate of only 15% to 18%. Patients with bone marrow invasion, positive margins, or pelvic node metastases had a median survival of only 10 months.
CONCLUSIONS: Pelvic recurrence of rectal cancer can be resected safely with expectation of long-term survival of 33%. Patient selection based on known risk factors can identify patients most likely to benefit from resection and eliminate those who should be treated for palliation only.
O A Ogunbiyi, K McKenna, E H Birnbaum, J W Fleshman, I J Kodner
Aggressive surgical management of recurrent rectal cancer--is it worthwhile?
Dis Colon Rectum. 1997 Feb;40(2):150-5.
Abstract/Text
OBJECTIVE: The purpose of this study was to determine whether radical surgery in appropriately selected patients who have recurrent rectal cancer can produce significant disease-free survival.
PATIENTS AND METHODS: This is a retrospective review of the management of all patients presenting with recurrent local and metastatic rectal cancer at a single institution during an 11-year period.
RESULTS: Of 489 patients who underwent curative surgery for primary rectal cancer during the period reviewed, 44 (9 percent) developed recurrent disease at a median interval of 18 (range, 3-60) months after curative surgery. Local pelvic recurrence alone was present in 28 (5.7 percent) patients. Overall survival after diagnosis of recurrent disease was 41 percent (18/44) at a median interval of 15 (range, 2-60) months. Curative resection was performed in 14 (32 percent) patients with a disease-free survival of 86 percent (12/14) at a median of 25 (range, 9-60) months after curative surgery. In comparison, survival in patients who underwent palliative treatment was significantly less (25 vs. 12 months; P < 0.05; 95 percent confidence interval, 10, 23 (Mann-Whitney U test)); 20 percent survival at a median of 12 months ranged from 2 to 36 after diagnosis of recurrent disease. Of six patients in the curative group who developed second recurrences, four underwent further curative surgery and are disease-free at a median of 19.5 (range, 12-29) months after surgery. Palliative surgery provided good symptomatic relief and improved quality of life in 11 patients in the palliative group, although there was no survival advantage over those who underwent nonsurgical palliative treatment (n = 19).
CONCLUSION: In appropriately selected cases, aggressive surgical therapy produces significant disease-free survival in patients with recurrent rectal cancer.
森谷冝皓，山口高史，赤須孝之ほか：骨盤内局所再発癌に対する積極的外科治療．臨外 2001; 56: 759－765.
Antonio M Lacy, Juan C García-Valdecasas, Salvadora Delgado, Antoni Castells, Pilar Taurá, Josep M Piqué, Josep Visa
Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: a randomised trial.
Lancet. 2002 Jun 29;359(9325):2224-9. doi: 10.1016/S0140-6736(02)09290-5.
Abstract/Text
BACKGROUND: Although early reports on laparoscopy-assisted colectomy (LAC) in patients with colon cancer suggested that it reduces perioperative morbidity, its influence on long-term results is unknown. Our study aimed to compare efficacy of LAC and open colectomy (OC) for treatment of non-metastatic colon cancer in terms of tumour recurrence and survival.
METHODS: From November, 1993, to July, 1998, all patients with adenocarcinoma of the colon were assessed for entry in this randomised trial. Adjuvant therapy and postoperative follow-up were the same in both groups. The main endpoint was cancer-related survival. Data were analysed according to the intention-to-treat principle.
FINDINGS: 219 patients took part in the study (111 LAC group, 108 OC group). Patients in the LAC group recovered faster than those in the OC group, with shorter peristalsis-detection (p=0.001) and oral-intake times (p=0.001), and shorter hospital stays (p=0.005). Morbidity was lower in the LAC group (p=0.001), although LAC did not influence perioperative mortality. Probability of cancer-related survival was higher in the LAC group (p=0.02). The Cox model showed that LAC was independently associated with reduced risk of tumour relapse (hazard ratio 0.39, 95% CI 0.19-0.82), death from any cause (0.48, 0.23-1.01), and death from a cancer-related cause (0.38, 0.16-0.91) compared with OC. This superiority of LAC was due to differences in patients with stage III tumours (p=0.04, p=0.02, and p=0.006, respectively).
INTERPRETATION: LAC is more effective than OC for treatment of colon cancer in terms of morbidity, hospital stay, tumour recurrence, and cancer-related survival.
Christopher M Schlachta, Joseph Mamazza, Eric C Poulin
Are transverse colon cancers suitable for laparoscopic resection?
Surg Endosc. 2007 Mar;21(3):396-9. doi: 10.1007/s00464-006-9042-6. Epub 2006 Nov 14.
Abstract/Text
BACKGROUND: The large randomized trials reporting on laparoscopic versus open colon surgery for cancer have all excluded patients with transverse colon cancer lesions. This study was undertaken to review our experience with surgery for curable transverse colon cancer.
METHODS: A database of 938 laparoscopic colon resections performed between April 1991 and September 2004 was reviewed. Of 514 procedures for cancer, stage IV disease, mid to low rectal cancers, and total colectomies were excluded. On an intent-to-treat basis, outcomes of surgery for transverse colon lesions (TC) were compared with outcomes of segmental colon resections for other lesions (OC).
RESULTS: A total of 22 TC were resected compared with 285 OC. Patients with TC were similar to patients with OC in age, gender, weight, and body mass index (BMI). Cancer stage was equivalent between patients with TC (9 Stage I, 7 Stage II, 6 Stage III) and OC (66 Stage I, 126 Stage II, 93 Stage III, p = 0.170) as was tumor size. Patients with TC underwent 9 transverse colectomies, 12 extended right hemicolectomies, and 1 extended left hemicolectomy. Patients with OC underwent 126 right hemicolectomies, 24 left hemicolectomies, and 135 sigmoid colectomies or anterior resections. There were no differences in conversion rate (18.2% vs. 13.3%, p = 0.752) or in intraoperative (9% vs. 8%, p = 0.814) or postoperative (41% vs. 30%, p = 0.418) complications. Operating time was longer with TC (209 +/- 63 min vs. 176 +/- 60 min, p = 0.042) and lymph node harvest was higher (15.3 +/- 11.6 vs. 10.8 +/- 7.6, p = 0.011). At a median followup of 17.2 months and 17.1 months, respectively, there were two (9%) recurrences after resection of TC and 17 (6%) recurrences after resection of OC.
CONCLUSIONS: Laparoscopic resection of transverse colon cancers is technically feasible and not associated with a significantly higher rate of complications or conversions or with impaired oncologic outcomes compared with patients having segmental laparoscopic resections for other colon cancers. Operating time is longer.
Iván Arteaga González, Antonio Martín Malagón, Eudaldo M López-Tomassetti Fernández, Javier Arranz Durán, Hermógenes Díaz Luis, Angel Carrillo Pallares
Impact of previous abdominal surgery on colorectal laparoscopy results: a comparative clinical study.
Surg Laparosc Endosc Percutan Tech. 2006 Feb;16(1):8-11. doi: 10.1097/01.sle.0000202188.57537.07.
Abstract/Text
To assess the results of laparoscopic colorectal surgery in patients who have previously undergone abdominal surgery. Between November 2002 and June 2004, 86 patients underwent laparoscopic surgery for colorectal disease at our hospital. Patients were divided into 2 groups depending on whether they had previously undergone abdominal surgery (previous surgery group, n = 27) or not (nonprevious surgery group, n = 59). Data were prospectively collected for statistical analyses of demographic, clinical, and histologic variables. Groups were comparable in age, body mass index, American Society of Anesthesiologists score, diagnosis, technique performed, and tumor size and distance to anal verge. There was no difference in perioperative complication rates. A higher conversion rate was found in the previous surgery group (26.1% vs. 5.1%, P = 0.02). In patients with tumor diseases, resection evaluations were no different regarding specimen length, distal and radial resection margins, or number of lymph nodes harvested. Laparoscopic colorectal surgery has proved to be a reliable technique for patients who have previously undergone abdominal surgery, its results comparable to those obtained with patients who have not.
Pierre J Guillou, Philip Quirke, Helen Thorpe, Joanne Walker, David G Jayne, Adrian M H Smith, Richard M Heath, Julia M Brown, MRC CLASICC trial group
Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicentre, randomised controlled trial.
Lancet. 2005 May 14-20;365(9472):1718-26. doi: 10.1016/S0140-6736(05)66545-2.
Abstract/Text
BACKGROUND: Laparoscopic-assisted surgery for colorectal cancer has been widely adopted without data from large-scale randomised trials to support its use. We compared short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer to predict long-term outcomes.
METHODS: Between July, 1996, and July, 2002, we undertook a multicentre, randomised clinical trial in 794 patients with colorectal cancer from 27 UK centres. Patients were allocated to receive laparoscopic-assisted (n=526) or open surgery (n=268). Primary short-term endpoints were positivity rates of circumferential and longitudinal resection margins, proportion of Dukes' C2 tumours, and in-hospital mortality. Analysis was by intention to treat. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN74883561.
FINDINGS: Six patients (two [open], four [laparoscopic]) had no surgery, and 23 had missing surgical data (nine, 14). 253 and 484 patients actually received open and laparoscopic-assisted treatment, respectively. 143 (29%) patients underwent conversion from laparoscopic to open surgery. Proportion of Dukes' C2 tumours did not differ between treatments (18 [7%] patients, open vs 34 [6%], laparoscopic; difference -0.3%, 95% CI -3.9 to 3.4%, p=0.89), and neither did in-hospital mortality (13 [5%] vs 21 [4%]; -0.9%, -3.9 to 2.2%, p=0.57). Apart from patients undergoing laparoscopic anterior resection for rectal cancer, rates of positive resection margins were similar between treatment groups. Patients with converted treatment had raised complication rates.
INTERPRETATION: Laparoscopic-assisted surgery for cancer of the colon is as effective as open surgery in the short term and is likely to produce similar long-term outcomes. However, impaired short-term outcomes after laparoscopic-assisted anterior resection for cancer of the rectum do not yet justify its routine use.
大腸癌研究会編：大腸癌治療ガイドライン 医師用 2022年版、金原出版、2022年.
A P Stillwell, P G Buettner, Y H Ho
Meta-analysis of survival of patients with stage IV colorectal cancer managed with surgical resection versus chemotherapy alone.
World J Surg. 2010 Apr;34(4):797-807. doi: 10.1007/s00268-009-0366-y.
Abstract/Text
BACKGROUND There is no consensus regarding the appropriate management of asymptomatic and minimally symptomatic patients with stage IV colorectal cancer and irresectable metastases. METHODS A literature search was conducted on Medline and Embase. Outcome measures included: survival; postoperative morbidity and mortality; complications from the primary tumor and the need for surgery to manage complications; the likelihood of curative surgery after initial response to primary therapy; and length of hospital stay. Quantitative meta-analysis was performed where appropriate. RESULTS Eight retrospective studies, including 1,062 patients, met the criteria for inclusion in this study. Meta-analysis has shown an improvement in the survival of patients managed with palliative resection of their primary tumor, with an estimated standardized median difference of 6.0 months (standardized difference, 0.55; 95% confidence interval (CI), 0.29, 0.82; p < 0.001). Patients managed with chemotherapy alone were 7.3 times more likely to have a complication from the primary tumor (95% CI, 1.7, 34.4; p = 0.008). There was no difference in the response rates to chemotherapy, making metastatic disease amendable to curative resection (0.85; 95% CI 0.40, 1.8; p = 0.662). CONCLUSIONS To date, only retrospective data are available, showing that palliative resection of the primary tumor in asymptomatic or minimally symptomatic patients with stage IV colorectal cancer is associated with longer survival. Resection of the primary tumor reduces the likelihood of complications from the primary tumor and avoids the need for emergency procedures.
Sabine Venderbosch, Johannes H de Wilt, Steven Teerenstra, Olaf J Loosveld, Aart van Bochove, Harm A Sinnige, Geert-Jan M Creemers, Margot E Tesselaar, Linda Mol, Cornelis J A Punt, Miriam Koopman
Prognostic value of resection of primary tumor in patients with stage IV colorectal cancer: retrospective analysis of two randomized studies and a review of the literature.
Ann Surg Oncol. 2011 Nov;18(12):3252-60. doi: 10.1245/s10434-011-1951-5. Epub 2011 Aug 6.
Abstract/Text
BACKGROUND: In patients with metastatic colorectal cancer (mCRC) with an asymptomatic primary tumor, there is no consensus on the indication for resection of the primary tumor.
METHODS: A retrospective analysis was performed on the outcome of stage IV colorectal cancer (CRC) patients with or without resection of the primary tumor treated in the phase III CAIRO and CAIRO2 studies. A review of the literature was performed.
RESULTS: In the CAIRO and CAIRO2 studies, 258 and 289 patients had undergone a primary tumor resection and 141 and 159 patients had not, respectively. In the CAIRO study, a significantly better median overall survival and progression-free survival was observed for the resection compared to the nonresection group, with 16.7 vs. 11.4 months [P<0.0001, hazard ratio (HR) 0.61], and 6.7 vs. 5.9 months (P=0.004; HR 0.74), respectively. In the CAIRO2 study, median overall survival and progression-free survival were also significantly better for the resection compared to the nonresection group, with 20.7 vs. 13.4 months (P<0.0001; HR 0.65) and 10.5 vs. 7.8 months (P=0.014; HR 0.78), respectively. These differences remained significant in multivariate analyses. Our review identified 22 nonrandomized studies, most of which showed improved survival for mCRC patients who underwent resection of the primary tumor.
CONCLUSIONS: Our results as well as data from literature indicate that resection of the primary tumor is a prognostic factor for survival in stage IV CRC patients. The potential bias of these results warrants prospective studies on the value of resection of primary tumor in this setting; such studies are currently being planned.
Yukihide Kanemitsu, Kohei Shitara, Junki Mizusawa, Tetsuya Hamaguchi, Dai Shida, Koji Komori, Satoshi Ikeda, Hitoshi Ojima, Hideyuki Ike, Akio Shiomi, Jun Watanabe, Yasumasa Takii, Takashi Yamaguchi, Kenji Katsumata, Masaaki Ito, Junji Okuda, Ryoji Hyakudomi, Yasuhiro Shimada, Hiroshi Katayama, Haruhiko Fukuda, JCOG Colorectal Cancer Study Group
Primary Tumor Resection Plus Chemotherapy Versus Chemotherapy Alone for Colorectal Cancer Patients With Asymptomatic, Synchronous Unresectable Metastases (JCOG1007; iPACS): A Randomized Clinical Trial.
J Clin Oncol. 2021 Apr 1;39(10):1098-1107. doi: 10.1200/JCO.20.02447. Epub 2021 Feb 9.
Abstract/Text
PURPOSE: It remains controversial whether primary tumor resection (PTR) before chemotherapy improves survival in patients with colorectal cancer (CRC) with asymptomatic primary tumor and synchronous unresectable metastases.
PATIENTS AND METHODS: This randomized phase III study investigated the superiority of PTR followed by chemotherapy versus chemotherapy alone in relation to overall survival (OS) in patients with unresectable stage IV asymptomatic CRC and three or fewer unresectable metastatic diseases confined to the liver, lungs, distant lymph nodes, or peritoneum. Chemotherapy regimens of either mFOLFOX6 plus bevacizumab or CapeOX plus bevacizumab were decided before study entry. The primary end point was OS, which was analyzed by intention-to-treat.
RESULTS: Between June 2012 and September 2019, a total of 165 patients were randomly assigned to either chemotherapy alone (84 patients) or PTR plus chemotherapy (81 patients). When the first interim analysis was performed in September 2019 with 50% (114/227) of the expected events observed among 160 patients at the data cutoff date of June 5, 2019, the Data and Safety Monitoring Committee recommended early termination of the trial because of futility. With a median follow-up of 22.0 months, median OS was 25.9 months (95% CI, 19.9 to 31.5) in the PTR plus chemotherapy arm and 26.7 (95% CI, 21.9 to 32.5) in the chemotherapy-alone arm (hazard ratio, 1.10; 95% CI, 0.76 to 1.59; one-sided P = .69). Three postoperative deaths occurred in the PTR plus chemotherapy arm.
CONCLUSION: Given that PTR followed by chemotherapy showed no survival benefit over chemotherapy alone, PTR should no longer be considered a standard of care for patients with CRC with asymptomatic primary tumors and synchronous unresectable metastases.
