The survival outcome of patients with metastatic colorectal cancer based on the site of metastases and the impact of molecular markers and site of primary cancer on metastatic pattern

Prasanna, Thiru; Karapetis, Christos S.; Roder, David; Tie, Jeanne; Padbury, Robert; Price, Timothy; Wong, Rachel; Shapiro, Jeremy; Nott, Louise M.; Lee, Margaret; Chua, Yu Jo; Craft, Paul; Piantadosi, Cynthia; Sorich, Michael J.; Gibbs, Peter; Yip, Desmond

doi:10.1080/0284186x.2018.1487581

Cited by 91 publications

(82 citation statements)

References 43 publications

(47 reference statements)

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“…Outcomes of patients with metastatic colorectal cancer (mCRC) have improved enormously over the last decade. Indeed, depending on the extent of metastases and the biology, the median OS of metastatic colorectal cancer patients can exceed 3 years [27]. There are different factors, which led to improved outcomes in patients with metastatic colorectal cancer: first, our knowledge of the tumor heterogeneity based on molecular profiling has changed the therapeutic management of these tumors.…”

Section: Discussionmentioning

confidence: 99%

Population-based SEER analysis of survival in colorectal cancer patients with or without resection of lung and liver metastases

2020

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Background: Approximately one third of all patients with CRC present with, or subsequently develop, colorectal liver metastases (CRLM). The objective of this population-based analysis was to assess the impact of resection of liver only, lung only and liver and lung metastases on survival in patients with metastatic colorectal cancer (mCRC) and resected primary tumor. Methods: Ten thousand three hundred twenty-five patients diagnosed with mCRC between 2010 and 2015 with resected primary were identified in the Surveillance, Epidemiology and End Results (SEER) database. Overall, (OS) and cancer-specific survival (CSS) were analyzed by Cox regression with multivariable, inverse propensity weight, near far matching and propensity score adjustment. Results: The majority (79.4%) of patients had only liver metastases, 7.8% only lung metastases and 12.8% metastases of lung and liver. 3-year OS was 44.5 and 27.5% for patients with and without metastasectomy (HR = 0.62, 95% CI: 0.58-0.65, P < 0.001). Metastasectomy uniformly improved CSS in patients with liver metastases (HR = 0.72, 95% CI: 0.67-0.77, P < 0.001) but not in patients with lung metastases (HR = 0.84, 95% CI: 0.62-1.12, P = 0.232) and combined liver and lung metastases (HR = 0.89, 95% CI: 0.75-1.06, P = 0.196) in multivariable analysis. Adjustment by inverse propensity weight, near far matching and propensity score and analysis of OS yielded similar results. Conclusions: This is the first SEER analysis assessing the impact of metastasectomy in mCRC patients with removed primary tumor on survival. The analysis provides compelling evidence of a statistically significant and clinically relevant increase in OS and CSS for liver resection but not for metastasectomy of lung or both sites.

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Section: Discussionmentioning

confidence: 99%

Population-based SEER analysis of survival in colorectal cancer patients with or without resection of lung and liver metastases

2020

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“…Organ-specific susceptibility of metastasis is common in CRC and is significantly associated with primary tumor location and BRAF, KRAS, and MSI status. 38 Peritoneal metastasis is associated with increased interferon-g levels and is surrounded by natural killer (NK) cells. 37 We previously found a correlation between Figure 4.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Mismatch Repair Status Between Primary and Matched Metastatic Sites in Patients With Colorectal Cancer

Wang¹,

Wang

et al. 2019

Journal of the National Comprehensive Cancer Network

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Background: Differences between the features of primary cancer and matched metastatic cancer have recently drawn attention in research. This study investigated the concordance in microsatellite instability (MSI) and mismatch repair (MMR) status between primary and corresponding metastatic colorectal cancer (CRC). Methods: Consecutive patients with metastatic CRC who had both primary and metastatic tumors diagnosed at our institution in January 2008 through December 2016 were identified. Immunohistochemistry was used to test the MMR status of both primary and matched metastatic tumors, and PCR analysis was performed to test MSI in patients with deficient MMR (dMMR) status. Results: A total of 369 patients were included. Of the 46 patients with MSI-high primary tumors, 37 (80.4%) also had MSI-high metastatic tumors, whereas 9 (19.6%) had microsatellite stable (MSS) metastatic tumors. A high concordance was found in patients with liver, lung, or distant lymph node metastases. Interestingly, the discrepancy was more likely to be limited to peritoneal (5/20) or ovarian (4/4) metastasis (chi-square test, P<.001). These organ-specific features were also found in the pooled analysis. Along with the change of MSI-high in primary cancer to MSS in metastatic cancer, lymphocyte infiltration decreased significantly (P=.008). However, the change did not influence survival; the median overall survival of MSI-high and MSS metastatic tumors was 21.3 and 21.6 months, respectively (P=.774). The discrepancy rate was 1.6% for patients with proficient MMR primary tumors. Conclusions: For patients with dMMR primary tumors, the concordance of MSI and MMR status in primary CRC and corresponding metastatic cancer is potentially organ-specific. High concordance is found in liver, lung, and distant lymph node metastases, whereas discrepancy is more likely to occur in peritoneal or ovarian metastasis. Rebiopsy to evaluate MSI-high/dMMR status might be needed during the course of anti–PD-1 therapy in cases of peritoneal or ovarian metastasis.

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“…The prognostic impact of the most common BRAF mutation in mCRC, BRAF V600E , is well characterized [129]. The survival rate of patients carrying the mutant form is decreased by approximately 50% compared to patients with wild-type BRAF (BRAF WT ) [130][131][132][133]. This is highlighted in a pooled analysis of the CAIRO, CAIRO2, COIN and Focus studies, where patients with BRAF mutations demonstrated worse median PFS and OS compared with patients that had BRAF WT tumors (PFS: 6.2 vs. 7.7 months, respectively; HR, 1.34; 95% CI, 1.17-1.54; p < 0.001; OS: 11.4 vs. 17.2 months, respectively; HR, 1.91; 95% CI, 1.66-2.19; p < 0.001) [133].…”

Section: Braf (V600e)mentioning

confidence: 99%

Personalized Medicine—Current and Emerging Predictive and Prognostic Biomarkers in Colorectal Cancer

Koulis

Yap

Engel

et al. 2020

Cancers

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Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide and is heterogeneous both morphologically and molecularly. In an era of personalized medicine, the greatest challenge is to predict individual response to therapy and distinguish patients likely to be cured with surgical resection of tumors and systemic therapy from those resistant or non-responsive to treatment. Patients would avoid futile treatments, including clinical trial regimes and ultimately this would prevent under- and over-treatment and reduce unnecessary adverse side effects. In this review, the potential of specific biomarkers will be explored to address two key questions—1) Can the prognosis of patients that will fare well or poorly be determined beyond currently recognized prognostic indicators? and 2) Can an individual patient’s response to therapy be predicted and those who will most likely benefit from treatment/s be identified? Identifying and validating key prognostic and predictive biomarkers and an understanding of the underlying mechanisms of drug resistance and toxicity in CRC are important steps in order to personalize treatment. This review addresses recent data on biological prognostic and predictive biomarkers in CRC. In addition, patient cohorts most likely to benefit from currently available systemic treatments and/or targeted therapies are discussed in this review.

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The survival outcome of patients with metastatic colorectal cancer based on the site of metastases and the impact of molecular markers and site of primary cancer on metastatic pattern

Abstract: Survival duration with mCRC is related to the site of metastases with lung limited disease showing a more favorable survival outcome compared to other single metastatic site disease. The BRAF mutation and primary rectal cancer were associated with poor prognostic metastatic sites.

Cited by 91 publications

References 43 publications

Population-based SEER analysis of survival in colorectal cancer patients with or without resection of lung and liver metastases

Population-based SEER analysis of survival in colorectal cancer patients with or without resection of lung and liver metastases

Comparison of Mismatch Repair Status Between Primary and Matched Metastatic Sites in Patients With Colorectal Cancer

Personalized Medicine—Current and Emerging Predictive and Prognostic Biomarkers in Colorectal Cancer

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