Metastasectomy For Colorectal Cancer Research Articles

Recurrence-free survival curve for pulmonary metastasectomy in colorectal cancer plateaus at 3years.

Pulmonary metastasectomy in colorectal cancer (CRC) has encouraging results; however, specific criteria for lung resection and the timing of resection remain undetermined. Therefore, in this study, we aimed to examine the long-term prognosis and 10-year survival rates and analyze poor prognostic factors in patients who underwent resection of pulmonary metastases from CRC. This retrospective, single-institution study included 156 patients with controlled primary CRC and metastases confined to the lungs or liver who underwent pulmonary metastasectomy between 2005 and 2022. Statistical analyses were conducted using the X2 and two-tailed Student's t test to compare variables. The receiver operating characteristic (ROC) curve was used to determine the appropriate cut-off point for tumor size as a predictive factor of survival. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and non-parametric group comparisons were performed using log-rank tests. The 5- and 10-year OS rates were 67% and 59%, respectively. Further, there was no recurrence 38months post-surgery, and the RFS curve plateaued. Moreover, by 88months post-surgery, no deaths occurred, and the OS curve plateaued. Multivariate analysis revealed that a pulmonary metastatic tumor >14mm and disease-free interval <2years indicated poor prognosis. The RFS curve for pulmonary metastasectomy may plateau approximately 3years after surgery. Pulmonary metastasectomy can achieve long-term survival in selected patients with CRC. Furthermore, surgical resection of recurrence after pulmonary metastasectomy may lead to better results. Thus, tumor size and disease-free interval may be independent prognostic factors.

Do children with Osteosarcoma benefit from Pulmonary Metastasectomy? - A Systematic Review Of Published Studies and 'Real world' Outcomes.

To critically examine the evidence-base for survival benefit of Pulmonary metastasectomy (PM) for Osteosarcoma (OS) in the paediatric population. PM for OS is recommended as standard of care in both paediatric and adult treatment protocols. Recent results from the PulMiCC trial demonstrate no survival benefit from Pulmonary Metastasectomy (PM) in Colorectal Cancer in adults. A systematic review was undertaken according to PRISMA guidelines. Medline, Embase and 2 clinical trials registers were searched for ALL STUDIES detailing paediatric OS patients (<18y) undergoing PM with a comparison cohort group that did not receive PM. Eleven studies met inclusion criteria dating from 1984 - 2017. All studies were retrospective and none directly compared PM versus No PM in paediatric patients as its main objective(s). Three-year survival rates ranged from 0-54% for PM and 0-16% for no PM. No PM patients were usually those with unresectable disease and/or considered to have a poor prognosis. All studies were at high risk of bias and there was marked heterogeneity in the patient selection. There is a weak evidence-base (Level IV) for a survival benefit of PM for OS in paediatric patients likely due to selection bias of 'favourable cases'. The included studies many of which detailed outdated treatment protocols were not designed in their reporting to specifically address the questions directly. A randomised controlled trial - whilst ethically challenging in a paediatric population - incorporating modern OS chemotherapy protocols is needed to crucially address any 'survival benefit'.

Lung Metastasectomy from Colorectal Cancer, 10-year Experience in a South American Cancer Center

PurposeThis study aimed to describe the survival outcomes and factors associated with prognosis in patients undergoing pulmonary metastasectomy with colorectal cancer (CRC) in a cancer center in South America.Material and methodsA retrospective analysis of patients that underwent lung metastasectomy due to CRC at National Cancer Institute (INC), Colombia between 2007 and 2017 was performed and Kaplan-Meier survival analysis along with log-rank test and Cox regression multivariate analysis were completed.ResultsSeventy-five patients with colorectal adenocarcinoma were included in the study. Of them, 57.3% were women with a median age of 62 years [interquartile ranges (IQR): 18.5]. For 45.3% the adenocarcinoma was located in the rectum and 29.3% had stage IV at diagnosis. 56% had a history of controlled extrapulmonary metastasis and 20% of the cases had a history of the metastasis of the liver. The median follow-up was 36.8 months (IQR: 27.4). Three-year and five-year overall survival (OS) was 57.5% [95% confidence interval (CI), 47.0–70.4] and 33.2% (95% CI, 23.4–47.2), respectively. Patients with bilateral, more than one pulmonary metastasis, abnormal postmetastasectomy carcinoembryonic antigen (CEA), history of liver metastasis, and disease-free interval (DFI) ≤12 months had worse OS. Three-year and five-year disease-free survival (DFS) was 30.1% (95% CI, 20.8–43.6) and 21.6% (95% CI, 13.0–35.9), respectively. Bilateral, more than one pulmonary metastasis, and patients with stage IV at diagnosis had the worst DFS. Multivariate analysis in the Cox regression model showed that abnormal postmetastasectomy CEA [Hazard Ratio (HR):1.97, 95% CI, 1.01–3.86, p = 0.045] and DFI ≤ 12 months (HR: 3.08, 95% CI, 1.26–7.53, p = 0.014) were independent factors for worst OS.ConclusionsThe OS found falls within the wide range described in the world literature but interestingly it falls at the bottom end of this range. The factors associated with worst survival were identified as bilateral, more than one pulmonary metastasis, abnormal postmetastasectomy CEA, history of liver metastasis, and DFI ≤12 months.Contribution to the fieldPulmonary metastasectomy is the standard of care in patients with metastatic CRC. However, the literature supporting this conduct is based on retrospective studies and the only randomized controlled trial conducted to date was stopped due to poor recruitment. Limited information is available in South America about survival and factors associated with prognosis in patients with metastatic CRC. While this study is another series that adds to the many studies across the world that describe the use of pulmonary metastasectomy in CRC, it presents critical data as it is one of the few studies carried out in South America. As described in a wide range of world literature, OS found falls in patients that underwent lung metastasectomy due to CRC however; interestingly, in the South American population analyzed here it falls at the bottom end of this range. This may be explained by a large number of patients included with a history of extrapulmonary metastasis as well as may reflect inadequate patient access to reference cancer centers in Colombia. Factors associated with worst survival in our population were bilateral, more than one pulmonary metastasis, abnormal postmetastasectomy CEA, history of liver metastasis, and interval from diagnosis to development of pulmonary metastasis ≤12 months.

Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) randomized controlled trial: a systematic review of published responses.

The objective of this review was to assess the nature and tone of the published responses to the Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) randomized controlled trial. Published articles that cited the PulMiCC trial were identified from Clarivate Web of Science (©. Duplicates and self-citations were excluded and relevant text was extracted. Four independent researchers rated the extracts independently using agreed scales for the representativeness of trial data and the textual tone. The ratings were aggregated and summarized. Two PulMiCC authors carried out a thematic analysis of the extracts. Sixty-four citations were identified and relevant text was extracted and examined. The consensus rating for data inclusion was a median of 0.25 out of 6 (range 0-5.25, interquartile range 0-1.5) and, for textual tone, the median rating was 1.87 out of 6 (range 0-5.75, interquartile range 1-3.5). The majority of citations did not provide adequate representation of the PulMiCC data and the overall textual tone was dismissive. Although some were supportive, many discounted the findings because the trial closed early and was underpowered to show non-inferiority. Two misinterpreted the authors' conclusions but there was an acceptance that 5-year survival was much higher than widely assumed. Published comments reveal a widespread reluctance to consider seriously the results of a carefully conducted randomized trial. This may be because the results challenge accepted practice because of 'motivated reasoning', but there is a widespread misunderstanding of the fact that though PulMiCC with 93 patients was underpowered to test non-inferiority, it still provides reliable evidence to undermine the widespread belief in a major survival benefit from metastasectomy.

Stereotactic Ablative Radiotherapy for Oligometastatic Disease: Great Enthusiasm but Scant Evidence

The prospective study Pulmonary Metastasectomy in Colorectal Cancer (N = 391) showed that expert selection was made on known prognostic features – number of metastases, tumour markers, liver involvement, interval – and patient performance and outcomes replicated follow-up studies. In the nested controlled trial all factors were well balanced and no survival difference remained.

The Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) trial results cast doubt upon benefit of lung and liver metastasectomy at the time colorectal resection

The Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) trial results cast doubt upon benefit of lung and liver metastasectomy at the time colorectal resection

The Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) burden of care study: Analysis of local treatments for lung metastases and systemic chemotherapy in 220 patients in the PulMiCC cohort.

The aim of this work was to examine the burden of further treatments in patients with colorectal cancer following a decision about lung metastasectomy. Five teams participating in the Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) study provided details on subsequent local treatments for lung metastases, including the use of chemotherapy. For patients in three groups (no metastasectomy, one metastasectomy or multiple local interventions), baseline factors and selection criteria for additional treatments were examined. The five teams recruited 220 patients between October 2010 and January 2017. No lung metastasectomy was performed in 51 patients, 114 patients had one metastasectomy and 55 patients had multiple local interventions. Selection for initial metastasectomy was associated with nonelevated carcinoembryonic antigen, fewer metastases and no prior liver metastasectomy. These patients also had better Eastern Cooperative Oncology Group scores and lung function at baseline. Four sites provided information on chemotherapy in 139 patients: 79 (57%) had one to five courses of chemotherapy, to a total of 179 courses. The patterns of survival after one or multiple metastasectomy interventions showed evidence of guarantee-time bias contributing to an impression of benefit over no metastasectomy. After repeated metastasectomy, a significantly higher risk of death was observed, with no apparent reduction in chemotherapy usage. Repeated metastasectomy is associated with a higher risk of death without reducing the use of chemotherapy. Continued monitoring without surgery might reassure patients with indolent disease or allow response assessment during systemic treatment. Overall, the carefully collected information from the PulMICC study provides no indication of an important survival benefit from metastasectomy.

What have we learned in the process of setting up and running the PulMiCC (Pulmonary Metastasectomy in Colorectal Cancer) randomised controlled trial?

What have we learned in the process of setting up and running the PulMiCC (Pulmonary Metastasectomy in Colorectal Cancer) randomised controlled trial?

The Pulmonary Metastasectomy in Colorectal Cancer cohort study: Analysis of case selection, risk factors and survival in a prospective observational study of 512 patients.

AimWe wanted to examine survival in patients with resected colorectal cancer (CRC) whose lung metastases are or are not resected.MethodsTeams participating in the study of Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) identified potential candidates for lung metastasectomy and invited their consent to join Stage 1. Baseline data related to CRC and fitness for surgery were collected. Eligible patients were invited to consent for randomization in the PulMiCC randomized controlled trial (Stage 2). Sites were provided with case report forms for non‐randomized patients to record adverse events and death at any time. They were all reviewed at 1 year. Baseline and survival data were analysed for the full cohort.ResultsTwenty‐five clinical sites recruited 512 patients from October 2010 to January 2017. Data collection closed in October 2020. Before analysis, 28 patients with non‐CRC lung lesions were excluded and three had withdrawn consent leaving 481. The date of death was known for 292 patients, 136 were alive in 2020 and 53 at earlier time points. Baseline factors and 5‐year survival were analysed in three strata: 128 non‐randomized patients did not have metastasectomy; 263 had elective metastasectomy; 90 were from the randomized trial. The proportions of solitary metastases for electively operated and non‐operated patients were 69% and 35%. Their respective 5‐year survivals were 47% and 22%.ConclusionSurvival without metastasectomy was greater than widely presumed. Difference in survival appeared to be largely related to selection. No inference can be drawn about the effect of metastasectomy on survival in this observational study.

The evidence for surgical interventions: Lung metastasectomy outcomes in the PulMiCC trial, an observational cohort study, and big data analysis

We enjoyed the thought provoking literary essay from Brendan Moran and Glen Guerra. Gaining acceptance of innovative ideas can be an uphill struggle, but convincing practitioners to discontinue ineffective therapies can be even more difficult. And in fairness to the many PulMiCC trialists (Pulmonary Metastasectomy in Colorectal Cancer) their hard-won evidence should be considered more thoughtfully, rather than dismissed in a few words with an outdated citation.

Pulmonary Metastasectomy in Colorectal Cancer: A Population-Based Retrospective Cohort Study Using the Korean National Health Insurance Database.

PurposeThe study aimed to investigate the current status and prognostic factors for overall survival in patients who had undergone pulmonary metastasectomy for colorectal cancer.Materials and MethodsThe data of 2,573 patients who had undergone pulmonary metastasectomy after surgery for colorectal cancer between January 2009 and December 2014 were extracted from the Korean National Health Insurance Service claims database. Patient-, colorectal cancer–, pulmonary metastasis–, and hospital-related factors were analyzed using the Kaplan-Meier method, log-rank test, and Cox proportional hazards analysis to identify prognostic factors for overall survival after pulmonary metastasectomy.ResultsThe mean age of the patients was 60.9±10.5 years; 66.2% and 79.1% of the participants were male and had distally located colorectal cancer, respectively. Wedge resection (71.7%) was the most frequent extent of pulmonary resection; 21.8% of the patients underwent repeated pulmonary metastasectomies; 73% of pulmonary metastasectomy cases were performed in tertiary hospitals; 53.9% of patients were treated in Seoul area; 82% of patients received chemotherapy in conjunction with pulmonary metastasectomy. The median survival duration was 51.8 months. The 3- and 5-year overall survival rates were 67.7% and 39.4%, respectively. In multivariate analysis, female sex, distally located colorectal cancer, pulmonary metastasectomy-only treatment, and high hospital volume (> 10 pulmonary metastasectomy cases/yr) were positive prognostic factors for survival.ConclusionPulmonary metastasectomy seemed to provide long-term survival of patients with colorectal cancer. The female sex, presence of distally located colorectal cancer, and performance of pulmonary metastasectomy in high-volume centers were positive prognostic factors for survival.

The Role of Obesity in Early and Long-Term Outcomes after Surgical Excision of Lung Oligometastases from Colorectal Cancer.

Obesity correlates with better outcomes in many neoplastic conditions. The aim of this study was to assess its role in the prognosis and morbidity of patients submitted to resection of lung oligometastases from colorectal cancer. Seventy-six patients undergoing a first pulmonary metastasectomy were retrospectively included in the study. Seventeen (22.3%) were obese (body mass index (BMI) >30 kg/m2). Assessed outcomes were overall survival, time to recurrence, and incidence of post-operative complications. Median follow-up was 33 months (IQR 16–53). At follow-up, 37 patients (48.6%) died, whereas 39 (51.4%) were alive. A significant difference was found in the 3-year overall survival (obese 80% vs. non-obese 56.8%, p = 0.035). Competing risk analysis shows that the cumulative incidence of recurrence was not different between the two groups. Multivariate analysis reveals that the number of metastases (p = 0.028), post-operative pneumonia (p = 0.042), and DFS (p = 0.007) were significant predictors of death. Competing risk regression shows that no independent risk factor for recurrence has been identified. The complication rate was not different between the two groups (17.6% vs. 13.6%, p = 0.70). Obesity is a positive prognostic factor for survival after pulmonary metastasectomy for colorectal cancer. Overweight patients do not experience more post-operative complications. Our results need to be confirmed by large multicenter studies.

Pulmonary metastasectomy in colorectal cancer: PulMiCC and future trials.

Pulmonary metastasectomy in colorectal cancer: PulMiCC and future trials.

Pulmonary metastasectomy in colorectal cancer: health utility scores by EQ-5D-3L in a randomized controlled trial show no benefit from lung metastasectomy.

AimThe aim was to assess the health utility of lung metastasectomy in the treatment of patients with colorectal cancer (CRC) using the EQ-5D-3L questionnaire.MethodsMultidisciplinary CRC teams at 14 sites recruited patients to a two-arm randomized controlled trial—Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC). Remote randomization was used, stratified by site and with minimization for seven known confounders. Participants completed the EQ-5D-3L questionnaire together with other patient reported outcome measures at randomization and then again at 3, 6, 12 and 24 months. These were returned by post to the coordinating centre.ResultsBetween December 2010 and December 2016, 93 participants were randomized, 91 of whom returned questionnaires. Survival and patient reported quality of life have been published previously, revealing no significant differences between the trial arms. Described here are patient reported data from the five dimensions of the EQ-5D-3L and the visual analogue scale (VAS) health state. No significant difference was seen at any time point. The estimated difference between control and metastasectomy patients was −0.23 (95% CI –0.113, 0.066) for the composite 0 to 1 index scale based on the descriptive system and 0.123 (95% CI –7.24, 7.49) for the 0 to 100 VAS scale.ConclusionsFollowing lung metastasectomy for CRC, no benefit was demonstrated for health utility, which alongside a lack of a survival or quality of life benefit calls into question the widespread use of the procedure.

Pulmonary Metastasectomy in Colorectal Cancer: the PulMiCC randomised controlled trial.

Pulmonary Metastasectomy in Colorectal Cancer: the PulMiCC randomised controlled trial.

Pulmonary Metastasectomy in Colorectal Cancer: updated analysis of 93 randomized patients - control survival is much better than previously assumed.

AimLung metastases from colorectal cancer are resected in selected patients in the belief that this confers a significant survival advantage. It is generally assumed that the 5‐year survival of these patients would be near zero without metastasectomy. We tested the clinical effectiveness of this practice in Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC), a randomized, controlled noninferiority trial.MethodMultidisciplinary teams in 14 hospitals recruited patients with resectable lung metastases into a two‐arm trial. Randomization was remote and stratified according to site, with minimization for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, number of metastases and carcinoembryonic antigen level. The trial management group was blind to patient allocation until after intention‐to‐treat analysis.ResultsFrom 2010 to 2016, 93 participants were randomized. These patients were 35–86 years of age and had between one and six lung metastases at a median of 2.7 years after colorectal cancer resection; 29% had prior liver metastasectomy. The patient groups were well matched and the characteristics of these groups were similar to those of observational studies. The median survival after metastasectomy was 3.5 (95% CI: 3.1–6.6) years compared with 3.8 (95% CI: 3.1–4.6) years for controls. The estimated unadjusted hazard ratio for death within 5 years, comparing the metastasectomy group with the control group, was 0.93 (95% CI: 0.56–1.56). Use of chemotherapy or local ablation was infrequent and similar in each group.ConclusionPatients in the control group (who did not undergo lung metastasectomy) have better survival than is assumed. Survival in the metastasectomy group is comparable with the many single‐arm follow‐up studies. The groups were well matched with features similar to those reported in case series.

Colorectal cancer mutations are associated with survival and recurrence after pulmonary metastasectomy

While knowledge has grown extensively regarding the impact of mutations on colorectal cancer prognosis, their role in outcomes after pulmonary metastasectomy (PM) remains minimally understood. We sought to determine the prognostic role of mutant disease on survival and recurrence after metastasectomy. Patients with available tumor sequencing profiles who underwent PM for colorectal cancer at a single institution from 2011 to 2017 were reviewed. Various demographic and clinicopathologic factors, as well as mutational status, were tested in the Cox regression analyses to identify predictors of survival and disease-free survival (DFS). A total of 130 patients met inclusion criteria, among whom 78 (60%) were male and the mean age was 57 years. The median survival time and 5-year survival rate were 58.2 months and 47%, respectively. A single pulmonary nodule was present in 54%. Disease recurrence occurred for 87 (67%) patients, including 75 (58%) who had at least one lung recurrence after metastasectomy at a median time to recurrence of 19.4 months. Upon multivariable analysis, RAS and TP53 mutations were associated with shorter survival DFS, while APC is associated with prolonged survival. After metastasectomy for colorectal cancer, mutations in RAS, TP53, and APC play an important role in survival and recurrence.

A randomized, double-blinded, placebo-controlled multicenter phase II trial of adjuvant immunotherapy with tecemotide (L-BLP25) after R0/R1 hepatic colorectal cancer metastasectomy (LICC): Final results.

3537 Background: Hepatic metastasectomy is the only potential curative treatment option for stage IV colorectal cancer (CRC) limited to liver metastases (LM). After R0 resection of LM the high recurrence rate remains a major challenge. L-BLP25 is an antigen-specific cancer vaccine targeting mucin 1 (MUC1). The LICC trial aimed to improve survival outcome in mCRC patients (pts) after R0/R1 LM resection. Methods: This LICC trial, a binational, multicenter, double-blinded, placebo controlled phase II trial, included pts with stage IV LM limited CRC after resection of primary tumor and LM (R0/R1) within the last 8 weeks, ECOG 0/1 and adequate organ function. Pts were 2:1 randomized to receive L-BLP25 or placebo. L-BLP25 930 µg was administered as 8 weekly subcutaneous doses followed by 6 week maintenance intervals until recurrence or a maximum of 2 years. Cyclophosphamide 300 mg/m2 (CP) or matching saline (NS) was given intravenously 3 days prior to first L-BLP25/placebo. Co-primary endpoints were recurrence-free survival (RFS) and 3-year overall survival (OS), secondary endpoints were RFS and OS in subgroups with different MUC1 expression and safety. Differences in RFS and OS were analyzed with exploratory log-rank tests on the intention-to-treat population. Results: Of 121 pts enrolled between Oct 2011 and Dec 2014, 79 pts received L-BLP25+CP, 42 placebo+NS. Baseline characteristics were well balanced. Median age was 60 years. Median RFS was 6.1 (90% CI: 5.8-8.8) vs. 11.4 months (90% CI: 5.0-20.3) and estimated 3-year OS rate 69.1% vs. 79.1% for L-BLP25 and placebo, respectively. Two-factorial Cox regression models showed no impact of MUC1 expression or treatment on RFS or OS. The most common L-BLP25-related grade 3/4 adverse events were diarrhea, anemia and back pain. There was one death in the L-BLP25 arm due to Merkel cell carcinoma assessed by the investigator as being potentially related to vaccination. Conclusions: The LICC trial failed to meet its primary endpoint of significantly improving RFS and OS with L-BLP25. MUC1 expression was not associated with outcome. Clinical trial information: NCT01462513.

Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC): A Multi-Centre Randomized Clinical Trial

Background: Lung metastasectomy in the treatment of advanced colorectal cancer has been adopted and established without control data. Our aim was to test its effectiveness in a randomised trial. Methods: Multidisciplinary teams in 13 hospitals recruited participants with potentially resectable lung metastases to a multicentre 2-arm randomised trial comparing active monitoring with or without metastasectomy. Other treatments were as decided by the local team. Randomization was centralised with stratification by site and minimisation for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, the number of metastases, and carcinoembryonic antigen. The assigned arm was not disclosed to the trial management group until completion of analysis. Analysis was on intention to treat with a margin for non-inferiority of 10%. Findings: Between December 2010 and December 2016, 65 participants were randomised. Characteristics were well-matched in the two arms and similar to those in reported studies: age 35 to 86 (IQR 60 to 74); primary resection IQR 16 to 35 months previously; stage at resection T1, 2 or 3 in 3, 8 and 46; N1 or N2 in 31 and 26; unknown in 8. Lung metastases 1 to 5 (median 2); 16/65 had previous liver metastases; carcinoembryonic antigen normal in 55/65. There were no other interventions in the first 6 months, no cross overs from control to treatment, and no treatment related deaths or major adverse events. Hazard ratio for death within 5 years, comparing metastasectomy with control, was 0.82 (95%CI 0.43, 1.56). Interpretation: The small number (N=65) precludes a conclusive answer to the research question but the similar survival in metastasectomy and control arms challenges beliefs that there is a 35% survival difference that can be attributed to lung metastasectomy. Clinical Trial Number: Clintrial.gov number NCT01106261. Funding Statement: Cancer Research UK funding Grant No. C7678/A11393. PulMiCC was supported by the UK Thoracic Surgery Research Collaborative which includes the surgeons named as contributors Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Ethics approval was granted by the National Research Ethics Committee London – Hampstead 10/H0720/5.

A randomized, double-blinded, placebo-controlled multicenter phase II trial of adjuvant immunotherapy with tecemotide (L-BLP25) after R0/R1 hepatic colorectal cancer metastasectomy (LICC): Final results.

480 Background: Hepatic metastasectomy is the only potential curative treatment option for stage IV colorectal cancer (CRC) limited to liver metastases (LM). After R0 resection of LM the high recurrence rate remains a major challenge. L-BLP25 is an antigen-specific cancer vaccine targeting mucin 1 (MUC1). The LICC trial aimed to improve survival outcome in mCRC patients (pts) after R0/R1 LM resection. Methods: This LICC trial, a binational, multicenter, double-blinded, placebo controlled phase II trial, included pts with stage IV LM limited CRC after resection of primary tumor and LM (R0/R1) within the last 8 weeks, ECOG 0/1 and adequate organ function. Pts were 2:1 randomized to receive L-BLP25 or placebo. L-BLP25 930 µg was administered as 8 weekly subcutaneous doses followed by 6 week maintenance intervals until recurrence or a maximum of 2 years. Cyclophosphamide 300 mg/m2 (CP) or matching saline (NS) was given intravenously 3 days prior to first L-BLP25/placebo. Co-primary endpoints were recurrence-free survival (RFS) and 3-year overall survival (OS), secondary endpoints were RFS and OS in subgroups with different MUC1 expression and safety. Differences in RFS and OS were analyzed with exploratory log-rank tests on the intention-to-treat population. Results: Of 121 pts enrolled between Oct 2011 and Dec 2014, 79 pts received L-BLP25+CP, 42 placebo+NS. Baseline characteristics were well balanced. Median age was 60 years. Median RFS was 6.1 (90% CI: 5.8-8.8) vs. 11.4 months (90% CI: 5.0-20.3) and estimated 3-year OS rate 69.1% vs. 79.1% for L-BLP25 and placebo, respectively. Two-factorial Cox regression models showed no impact of MUC1 expression or treatment on RFS or OS. The most common L-BLP25-related grade 3/4 adverse events were diarrhea, anemia and back pain. There was one death in the L-BLP25 arm due to Merkel cell carcinoma assessed by the investigator as being potentially related to vaccination. Conclusions: The LICC trial failed to meet its primary endpoint of significantly improving RFS and OS with L-BLP25. MUC1 expression was not associated with outcome. Clinical trial information: NCT01462513 . Clinical trial information: NCT01462513.