Right-sided Colorectal Cancer Research Articles

Should Anti-EGFR Agents Be Used in Right-Sided RAS Wild-type Advanced Colorectal Cancer?

Colorectal cancer is the third most common cancer worldwide with a high mortality rate at the advanced stages of the disease. Treatment options are dependent on the stage of the disease, patients’ performance status, and the specific molecular makeup of the tumor. Adding an anti-epidermal growth factor receptor monoclonal antibody (anti-EGFR mAb) to conventional chemotherapy in molecularly selected patients (i.e., RAS wild-type) leads to a survival advantage. We aim to review the latest evidence on the influence of primary tumor location (PTL) on treatment response to chemotherapy combined with an anti-EGFR in patients with metastatic colorectal cancer (mCRC). Colon cancer arising on the left side versus the right side of the colon portrays different outcomes, emerging PTL as an important characteristic in understanding the outcomes for patients with colorectal cancer. Patients with right-sided tumors have a worse prognosis than those with left-sided tumors. Primary tumor location may also be predictive of treatment benefit from targeted therapy with an anti-EGFR or anti-VEGF in the treatment of RAS wild-type mCRC. Although no benefit in overall survival (OS) has been demonstrated, available data up to now can endorse the use of an anti-EGFR in right-sided RAS wild-type advanced colorectal cancer if the therapy goal is tumor shrinkage (given the higher objective response rate). However, the majority of data on PTL has been obtained through retrospective analysis of clinical trials where PTL was neither part of the stratification nor pre-planned subgroup analysis, rendering it susceptible to recall bias. There is a great necessity to improve our understanding of the molecular and histological variability in left versus right-sided colon cancer and its impact on future targeted therapy.

Primary tumour location affects survival after resection of colorectal liver metastases: A two-institutional cohort study with international validation, systematic meta-analysis and a clinical risk score.

BackgroundColorectal cancer (CRC) represents a major cause for cancer death and every third patient develops liver metastases (CRLM). Several factors including number and size of metastases and primary tumour lymph-node status have been linked to survival. The primary tumour location along the colo-rectum continuum (sidedness) was analysed in first-line chemotherapy trials, where right-sided CRCs showed decreased survival. This association has not yet been clearly established in patients undergoing resection for CRLM.MethodsClinicopathological differences in CRLM resections according to sidedness in two Austrian centres (2003–2016) are described and survival is compared through Kaplan-Meier and multivariable analysis. A risk-score is presented with time-dependent receiver operating curve analysis and international validation in two major hepatobiliary centres. Furthermore, a systematic meta-analysis of studies on primary tumour location and survival after CRLM resection was performed.Results259 patients underwent hepatectomy. Right-sided CRC patients (n = 59) more often had positive primary tumour lymph-nodes (76.3%/61.3%;p = 0.043) and RAS-mutations (60%/34.9%;p = 0.036). The median overall and disease-free survival was 33.5 and 9.1 months in right-sided versus 55.5 (p = 0.051) and 12.1 months (p = 0.078) in left-sided patients. In multivariable analysis nodal-status (HR 1.52), right-sidedness (HR 1.53), extrahepatic disease (HR 1.71) and bilobar hepatic involvement (HR 1.41) were significantly associated with overall survival. Sidedness was not independently associated with disease-free survival (HR 1.33; p = 0.099). A clinical risk score including right-sidedness, nodal-positivity and extrahepatic involvement significantly predicted overall (p = 0.005) and disease-free survival (p = 0.027), which was confirmed by international validation in 527 patients (p = 0.001 and p = 0.011). Meta-analysis including 10 studies (n = 4312) showed a significant association of right-sidedness with overall survival after resection (HR 1.55;p<0.001). There was no significant association with disease-free survival (HR 1.22;p = 0.077), except when rectal-cancers were excluded (HR 1.39;p = 0.006).ConclusionsPatients with liver metastases from right-sided CRC experience worse survival after hepatic resection. Sidedness is a simple yet effective factor to predict outcome.

FOLFOXIRI versus doublet-regimens in the first-line therapy of MSI-S right-sided (RS) metastatic colorectal cancer (mCRC): A survival analysis.

e15060 Background: Microsatellite stable (MSI-S) RS mCRC patients (pts) have a worse prognosis relative to left sided tumors for overall survival (OS). The present analysis aims to test the hypothesis that a triplet-regimen is superior compared to doublet-regimens (DR; FOLFOX or FOLFIRI) for OS. Methods: Pts with treatment-naive RS mCRC at MD Anderson Cancer Center between January/2011 to December/2018 were selected. We compared the progression-free survival (PFS) and OS of mCRC pts treated with FOLFOXIRI versus DR. Pts treated with anti-EGFR therapy were excluded. Results: A total of 37 pts were treated with FOLFOXIRI and 111 pts with DR. There were no statistical difference between groups regarding gender, KRAS and BRAF mutations, peritoneal metastasis and bevacizumab use. There were statistical difference in age (median: 46y vs 59y) and metastasectomy rates (14% vs 32%) (p &lt; 0.001). KRAS mutation was found in 65% of the population. Median follow-up was 55.3m. Median PFS was 6.5m vs 11.2m (HR: 1.30 95% CI 0.85 – 1.99) and median OS was 17.0m vs 26.3m (HR: 1.01 95% CI 0.60 – 1.68). By univariate analysis, pts who have undergone metastasectomy had superior PFS (14.9m vs 9.2m; p&lt;0.001) and OS (32.4m vs 22.9m; p=0.003). By multivariate analysis adjusted for age, BRAF mutation, metastasectomy, bevacizumab use and, treatment regimen, only age and metastasectomy had prognostic influence for PFS (p=0.039 and p=0.026, respectively). Conclusions: Despite RS having a poor prognosis for OS, our study does not suggest that RS mCRC pts benefit from intensive treatment. Randomized clinical trials may suggest more individualized therapies.

Value of tumor size as a prognostic factor in metastatic colorectal cancer patients after chemotherapy: a population-based study.

Aim: To evaluate the relationship between tumor size and survival in metastatic colorectal cancer (mCRC) patients who received chemotherapy. Materials & methods: SEER database was accessed for eligible patients. Multivariate Cox regression analysis was performed to compare the effect of tumor size on overall survival (OS) and CRC-specific survival (CCSS). Results: Tumor size ≥5cm was an independent risk factor for OS and CCSS in mCRC patients treated with chemotherapy. Tumor size <5cm did not show a survival advantage in patients whose primary tumor site was rectosigmoid junction, while tumor size ≥5cm was associated with poor OS and CCSS in left-and right-sided colorectal cancer. Conclusion: Tumor size ≥5cm was associated with poor prognosis after receiving chemotherapy treatment and a risk factor for survival of mCRC.

Population-based assessment of the performance of sigmoidoscopy in the detection of colorectal cancer: implications for future screening recommendations.

Current North American guidelines endorse the use of flexible sigmoidoscopy every 10 years as an alternative to fecal testing for the screening of colorectal cancer (CRC). The present study aims to evaluate its performance in a hypothetical population-based scenario, using data from the Surveillance, Epidemiology and End Results (SEER)-18 database. We explored the SEER database with the SEER*stat software. All cases diagnosed as colorectal carcinoma within the age group of 50-74 years during the year 2010 were included. Cases were considered either accessible or non-accessible to detection by screening sigmoidoscopy by virtue of their anatomic location. For example, cases within the rectum, sigmoid or descending colon were considered accessible whereas cases within other colorectal sub-sites were considered non-accessible. Assuming that all eligible United States' citizens underwent screening sigmoidoscopy and assuming that all CRC cases within accessible sites were correctly identified by sigmoidoscopy, true positive, true negative, and false negative cases were calculated. False positive cases, however, were non-calculable. Sensitivity and negative predictive value (NPV) of screening sigmoidoscopy were derived accordingly. A total of 18,794 patients aged between 50-74 years were diagnosed in 2010. The total United States' population covered by the SEER-18 registry in the same year and within the same age group was 21,613,411 individuals. A total of 10,786 CRC patients (57.4%) were diagnosed in sigmoidoscopy-accessible sites, 7,532 CRC patients (40.1%) were diagnosed in sigmoidoscopy-non-accessible sites, and an additional 476 patients (2.5%) were identified as unknown sub-sites. This translated into 2,853 CRC-related deaths at 5 years for sigmoidoscopy-accessible tumors versus 2,126 CRC-related deaths for sigmoidoscopy-non-accessible tumors. Based on the study's assumptions, sensitivity of screening sigmoidoscopy would be 58.8% and NPV would be 99.9%. Flexible sigmoidoscopy has an unacceptably low sensitivity for the detection of right-sided CRC; therefore, its use as a first-line screening modality should be questioned. Additional studies on alternative screening options for right-sided CRC are warranted.

Comparison of phosphoproteomic profiles in left- and right-sided colorectal cancers.

582 Background: Left- and right-sided colorectal cancers (CRCs) are different in terms of prognosis, treatment response and underlying molecular mechanisms. The aim of this study was to unravel the phosphoproteomic profiles of left- and right-sided primary CRCs and to identify potential drug targets for both primary tumor sites. Methods: In total phosphoproteomic profiles of 69 fresh-frozen biopsies, including 34 left-sided and 35 right-sided primary CRCs, were obtained by LC-MS/MS after cell lysis, digestion and phosphopeptide enrichment using anti-phosphotyrosine antibodies. MS/MS spectra were searched against a UniProt human reference proteome FASTA file using MaxQuant software. Fold changes between normalized intensities were calculated. Group comparison was performed using the R package Limma. P values below 0.01 and fold changes &gt; two were considered significant and biologically relevant. Results: In total 2,840 phosphopeptides were detected in at least 5% of the samples. Of these, 36 phosphopeptides were significantly upregulated and 14 were significantly downregulated in right-sided compared to left-sided CRCs using our stringent selection criteria. Since BRAF mutations and deficient DNA mismatch repair (dMMR) were more frequently observed in right-sided CRC (p &lt; 0.01), group comparison was repeated with MMR proficient CRCs only, resulting in 21 phosphopeptides up- and one downregulated in left- versus right-sided CRC. The identified phosphoproteins from the phosphopeptides included three FDA approved drug targets. Conclusions: Differences in phosphoproteomic profiles were detected between left- and right-sided CRCs, besides molecular differences such as BRAF mutation and MMR status. These results indicate that the molecular biology of left-and right-sided CRCs may explain their differences in clinical behavior and response to treatment.

Genetic Analysis Using a Gene Panel in 87 Caucasian Patients With Colorectal Cancer: Own Results and Review of Literature

Colorectal cancer (CRC) is the third most common cancer worldwide. The prognosis between left- and right-sided CRC differs, partly due to baseline differences as vascular supply. The purpose of the present study was to investigate whether there are genetic differences between left- and right-sided CRC. Eighty-seven patients with CRC (mean age: 61 years) were retrospectively included in the study. Blood samples were used for genetic analysis, by applying the sequencing research panel Ion AmpliSeq Colon and Lung Cancer Research Panel V2. Statistical analyses included Chi-square tests, Kaplan-Meier survival curves, and univariate/multivariate Cox-regression analyses. By testing the sequence of 22 genes included in the panel, a significant difference was detected between left- and right-sided CRC regarding the expression of BRAF and DDR2 genes, with mutations occurring more often in the right-sided CRC. In the multivariate setting, left-sided CRC only turned out as a significant positive prognostic parameter regarding progression-free survival, irrespective of the type of chemotherapy or BRAF and NRAS mutations. Tumour location was the only parameter proven to be an independent prognostic factor for CRC in the present study.

The impact of sidedness of colorectal cancer in tumor immunity.

584 Background: Clinical and molecular characteristics are different between Right-side and left-sided colorectal cancer (CRC). The aim of this study was to clarify the significance of the correlation of the Sidedness of CRC and tumor immunity. Methods: A total of 116 patients who underwent curative colectomy for stage II/III CRC were included in this study. The expression of PD-1, PD-L1, FoxP3, TGF-b, and IDO was examined by immunohistochemistry and the relationship of sidedness to several prognostic factors was examined. Results: In clinicopathological factors, there were no significant difference between right sided and left sided CRC except for differentiation. Regarding tumor immunity, there were no significant difference in PD-1 and IDO expression. However, Fox P3 (right side 72% vs. left side 59%) and TGFβ (right side 72% vs. left side 57%) tended to be highly expressed in right side(p &lt; 0.1). PDL1 was significantly highly expressed in right side(right side 65% vs. left side 35%, p &lt; 0.05). In OS and DFS, the patients with right sided tumor tended to have poor prognosis compared with left side (p &lt; 0.1). The PD-L1 positive patients of right-sided tumor had poor prognosis (p &lt; 0.05). Conclusions: Sidedness is associated with tumor immunity in colorectal cancer.

Left- versus right-side metastatic colorectal cancer: Teasing out clinicopathologic drivers of disparity in survival.

623 Background: Patients with metastatic colorectal cancer (mCRC) arising from a right sided colorectal cancer (RC) have an inferior survival versus patients with a left sided colorectal cancer (LC). Previous analyses have suggested that multiple factors contribute. Methods: The Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Registry has prospectively captured comprehensive data on consecutive mCRC patients since 2009. For this analysis LC were defined as primary tumors at or distal to the splenic flexure and included rectal cancers. We analysed patient, tumor, treatment and outcome data. Results: Of 2306 patients enrolled from July 2009–March 2018, median age 67 years (range 18–100), 1559 (67.6%) had a LC. Patients with a RC were older (median 71 vs 65 years, p &lt; 0.001), more likely to be female (50.2% vs 36.9%, p &lt; 0.001) and to have a Charlson score ≥ 3 (67.5% vs 54.6%, p &lt; 0.001). More common in RC, where tested, were BRAF mutations (22.3% vs 7.2%, p &lt; 0.001) and deficient mismatch repair (6.4% vs 1.5%, p &lt; 0.001), but not RAS mutations. Peritoneal metastases were more frequent in RC (29.7% vs 14.9%, p &lt; 0.001). RC patients were more likely to have their primary tumor resected (77.9% vs 70.6%, p &lt; 0.001) and to receive less first-line chemotherapy (72.2% vs 78.7%, p = 0.001). Progression-free survival on first-line systemic therapy was inferior for RC patients (8.1 vs 10.8 months, HR 1.38, p &lt; 0.001). Median overall survival (OS) for all RC patients was inferior (19.6 vs 27.5 months, HR 1.44, p &lt; 0.001). Primary side remained a significant factor for OS in multivariate analysis. Conclusions: Our data confirms the poor prognosis associated with RC, contributed to by multiple factors. However, primary side remains significant even when adjusting for these, indicating the existence of further as yet undefined differences. [Table: see text]

The Clinical Significance of Microsatellite Instability in Patients with Right-sided Colorectal Cancer.

Colorectal cancer (CRC) with microsatellite instability (MSI) has a better prognosis than CRC with microsatellite stable (MSS). Recent studies have reported biological differences according to tumor location in CRC. In this study, we investigated the clinical significance of MSI in patients with right-sided CRC. The medical records of 1,009 CRC patients diagnosed at our institute between October 2004 and December 2016 with MSI test results were retrospectively reviewed. The long-term outcomes of CRC patients with MSI were assessed with respect to tumor location using Kaplan-Meier curves and Cox regression models. The median follow-up duration for all 1,009 study subjects was 25 months (interquartile range, 15-38). One hundred twenty-four of the study subjects had MSI (12.3%) and 250 had right-sided CRC (24.8%). The patients with MSI and right-sided CRC had better disease-free survival (DFS) than those with MSS as determined by the log-rank test (p=0.013), and this result was significant in females (p=0.035) but not in males with right-sided CRC. Multivariate Cox regression analysis showed MSS significantly predicted poor DFS in patients with right-sided CRC (hazard ratio 3.97, 95% CI 1.30-12.15, p=0.016) and in female patients (hazard ratio 4.69, 95% CI 1.03-21.36, p=0.045). The study shows MSI is a useful predictor of DFS in patients with right-sided CRC, especially in female patients.

The Impact of Primary Tumor Sidedness on the Effect of Regorafenib in Refractory Metastatic Colorectal Cancer.

Recently, the sidedness of the primary tumor (right versus left) has been investigated for its ability to prognosticate and predict outcomes. We evaluated the effect of regorafenib based on KRAS mutation status and the sidedness of the primary tumor in patients with metastatic colorectal cancer (mCRC). We analyzed 135 patients with refractory metastatic colorectal cancer (mCRC) being treated with regorafenib at Samsung Medical Center, between January 2014 and January 2018. Primary tumors originating in the splenic flexure, descending colon, sigmoid colon, rectum, or proximal third of the transverse colon were defined as left-sided CRC (LC). Primary tumors originating in the appendix, cecum, ascending colon, hepatic flexure, or distal two-thirds of the transverse colon were defined as right-sided CRC (RC). Among all 135 patients, 100 (74.1%) had left sided colon cancer and 35 (25.9%) had right-sided colon cancer. No patients achieved a complete response, but four achieved a partial response, revealing a response rate (RR) of 3.0%. Thirty-seven patients had stable disease, yielding a disease control rate (DCR) of 30.4%. There was no difference in RR or DCR according to the location of the primary tumor (LC vs. RC). A significant difference in progression free survival (PFS) with regorafenib was observed between the LC and RC groups (2.6 months; 95% CI, 2.0 to 3.1 vs. 1.9 months; 95% CI, 1.6 to 2.3; P = 0.04, respectively). In a subpopulation with wild type KRAS, PFS with regorafenib was also significantly different between the LC and RC groups (2.9 months; 95% CI, 1.5 to 4.3 vs. 2.1 months; 95% CI, 0.6 to 3.6; P = 0.04). On multivariate analysis, the sidedness of the primary tumor (LC vs. RC) and the number of metastatic sites (≤1 vs. 2>) had a prognostic effect on PFS (P = 0.01 and P = 0.01, respectively). Regorafenib is a current standard treatment for CRC, but treatment outcomes may be improved if regorafenib is administered based on the appropriate biomarker.

Worse survival in liver metastatic right-sided versus left-sided colorectal cancer

Worse survival in liver metastatic right-sided versus left-sided colorectal cancer

Worse survival in liver metastatic right-sided versus left-sided colorectal cancer

Background: Colorectal cancer (CRC) is the third most common cancer and a quarter develop liver metastases (LM). Differences in epidemiological and molecular patterns between right- and left-sided colon cancer are emerging suggestive of a worse prognosis for right-sided cancer. The aim of the study was to describe the liver metastatic patterns and survival as a function of site of primary tumour. Methods: Patients diagnosed with CRC during 2008 in the region of Stockholm, Sweden, were identified through the Swedish Colorectal Cancer Register and followed for 5 years. Additional information on liver metastatic pattern were retrieved from patient electronic charts. Factors influencing overall survival (OS) were examined using Cox proportional hazards model with 95 per cent confidence interval (c.i.) and OS was compared using log-rank test. Results: LM were more often diagnosed in hindgut cancer (28.4% versus 22.1%, p=0.029) but the number and segmental involvement of LM were less extensive compared to midgut cancer (p=0.001). 5-year OS were significantly worse in liver metastatic midgut cancer compared to hindgut cancer (6.5% vs. 21.6%, p<0.001), still significant in the multivariate analysis of patients with LM (HR=0.56, c.i. 0.39 to 0.79). Conclusion: Detailed population-based data on the metastatic pattern of CRC and survival could assist in more structured and individualized guidelines for follow-up. The results are in agreement with previous publications on the worse prognosis for right-sided cancers.

Considering FOLFOXIRI plus bevacizumab for metastatic colorectal cancer with left-sided tumors.

A recent subgroup analysis of the TRIBE trial suggested that FOLFOXIRI plus bevacizumab may be a preferred option for the first-line treatment of only right-sided metastatic colorectal cancer (mCRC), regardless of RAS or BRAF status. Our subanalysis of a phase II trial of the FOLFOXIRI triplet regimen plus bevacizumab in patients with mCRC who had RAS mutant tumors showed that tumor shrinkage was better and the duration of treatment was longer in patients with left-sided tumors than in those with right-sided tumors, leading to a higher rate of conversion to surgery in mCRC patients with left-sided tumors. The early and deep responses to the triplet-regimen in patients with left-sided tumors might facilitate conversion treatment resulting in favorable survival. Our data suggest that the FOLFOXIRI plus bevacizumab might be a promising treatment for left-sided mCRC involving RAS mutant tumors.

Anti-EGFR Therapy in Right-Sided Metastatic Colorectal Cancer: Right or Wrong?

Anti-EGFR Therapy in Right-Sided Metastatic Colorectal Cancer: Right or Wrong?

Impact of Right-sided Primary Tumor Location Among Patients With Oligometastatic Colorectal Cancer Treated With Stereotactic Body Radiotherapy.

Among patients with colorectal cancer, those with right-sided primary tumors have worse outcomes in both the primary and metastatic setting. Patients with oligometastatic colorectal cancer (OMCC) have improved prognosis relative to those with diffusely metastatic disease. We aimed to assess if the trend toward worse outcomes with right-sided tumors remained in the oligometastatic setting. We analyzed 31 patients treated at a single institution with stereotactic body radiotherapy for OMCC from 2011 to 2014 to assess the impact that primary tumor location had on overall survival (OS) and progression-free survival (PFS). Overall, patient local control was fair (66% at 2 y); however, distant control was only 37.4% at 2 years. The median OS was 2.4 years; the median PFS was 6.5 months. Patients with right-sided primary tumors had numerically worse median OS than those with left-sided or rectal primary tumors (1.4 vs. 3.7 y, P=0.09). Median PFS was significantly worse among those with right-sided primaries (2.9 vs. 10.8 mo, P=0.05). This held on multivariate analysis. These results affirm that patients with OMCC have extended OS periods and that stereotactic body radiotherapy offers strong local control in these settings. We show that even in the oligometastatic setting those with right-sided primary tumors have worse outcomes relative to those with left-sided or rectal primary tumors. This suggests more aggressive treatment may be needed for those with oligometastatic right-sided colorectal cancer.

Differences in overall survival and mutation prevalence between right- and left-sided colorectal adenocarcinoma.

Prior reports have demonstrated inferior outcomes for patients with right-sided colorectal cancer (CRC) compared to patients with left-sided disease, as well as differences in treatment response based on disease sidedness. Differences in prognosis remain even among patients with metastatic disease, indicating that anatomy or stage at diagnosis alone cannot explain all of these findings. While genetic differences between right- and left-sided CRC have long been described, the genetic and molecular drivers underlying differences in prognosis and treatment response remain incompletely understood. We compared mutation prevalence between right- (cecum to splenic flexure) and left-sided (descending colon to rectum) CRC among 38 genes in a retrospective review of next-generation sequencing data of CRC samples obtained in routine clinical practice at a single academic medical center. Among 288 cases (167 left-sided, 103 right-sided, 18 synchronous or without clear primary), patients with left-sided primaries had a longer overall survival from pathologic diagnosis (median 1,823 days vs. 1,006 days for right-sided cases, P=0.004). Among the assessed genes, BRAF and CTNNB1 mutations were more prevalent in right-sided CRC. BRAF was mutated in 15.5% of right-sided CRC (95% CI: 8.5-22.5%) compared to 4.8% (95% CI: 1.6-8.0%) (P=0.003). CTNNB1 was mutated in 3.9% of right-sided CRC (95% CI: 0.2-7.6%) compared to no instances of CTNNB1 mutations in left-sided disease (P=0.01). This difference in mutation prevalence may implicate these genetic pathways in the mechanisms underlying the discrepant outcomes and treatment responses between right- and left-sided CRC described in this and prior studies.

589P - The prognostic value of KRAS, NRAS, BRAF and DNA mismatch repair (MMR) status in left- and right-sided metastatic colorectal cancer (mCRC): A Belgian population-based study

589P - The prognostic value of KRAS, NRAS, BRAF and DNA mismatch repair (MMR) status in left- and right-sided metastatic colorectal cancer (mCRC): A Belgian population-based study

The prognostic significance of the expression of monocarboxylate transporter 4 in patients with right- or left-sided colorectal cancer.

Monocarboxylate transporter 4 (MCT4) is a proton pump that exchanges lactate through the plasma membrane. The present study investigated the clinical significance of the expression of MCT4 in patients with right- or left-sided colorectal cancer (CRC). Surgical specimens from 237 CRC patients were immunohistochemically stained with polyclonal anti-MCT4 antibodies. The relationships among the MCT4 expression, the clinicopathological factors, and the prognosis were evaluated. Thirty-six (62.1%) of 58 patients with right-sided CRC and 95 (53.1%) of 179 patients with left-sided CRC showed the high expression of MCT4. The MCT4 expression was significantly correlated with gender and lymph node metastasis in patients with right-sided CRC, and size, depth of invasion, distant metastasis, and tumor-node-metastasis stage in patients with left-sided CRC. A univariate analysis demonstrated that the expression of MCT4 was a significant prognostic factor in both right- and left-sided CRC patients. A multivariate analysis demonstrated the expression of MCT4 was a significantly independent prognostic factor in patients with left-sided CRC, but not in those with right-sided CRC. Our results suggest that the high expression of MCT4 is a useful marker for tumor progression and a poor prognosis in CRC patients, especially those with left-sided CRC.

The location of the primary colon cancer has no impact on outcomes in patients undergoing cytoreductive surgery for peritoneal metastasis

BackgroundThe impact of the location of colorectal cancer on patient outcomes has been reported in several settings. The objective of this study was to assess the prognostic impact of the location of the primary colon cancer among patients with colorectal cancer peritoneal metastases undergoing complete cytoreductive surgery. MethodsUsing the prospectively maintained clinical and biological digestive peritoneal metastasis database of the BIG-RENAPE network, we identified 796 patients treated by a complete cytoreductive surgery between January 2004 and January 2017 for colorectal cancer peritoneal metastases in 16 different institutions. The 2 primary endpoints were overall survival and progression-free survival. To evaluate the impact on overall survival and progression-free survival of potential prognostic factors (including the location of the primary colorectal cancer), these factors were included in univariate and multivariate Cox proportional hazard models. ResultsRight-sided colorectal cancers were more often BRAF mutated and had microsatellite instability, whereas the frequency of RAS mutation was similar between right-sided and left-sided colorectal cancers. After a median follow-up time of 3.3 years, there was no significant difference in overall survival or progression-free survival according to tumor side. The lack of effect of tumor location on overall survival and progression-free survival was consistent across subgroups. ConclusionAmong patients undergoing complete cytoreductive surgery for peritoneal metastases, the site of the primary colorectal cancer was not associated with differences in progression-free survival or overall survival. Tumor side should not be used as a stratification factor in trials of colorectal cancer peritoneal metastases and should not be used in the selection process of patients for cytoreductive surgery.