30 Oct Prognostic Survival Associated With Left vs Right-Sided Colon Cancer
MedicalResearch.com Interview with:
Fausto Petrelli, MD
Oncology Unit, Oncology Department
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: This meta-analysis evaluated if side (excluding rectum site) represents an independent prognostic factor for survival in patients with stages 1-4 colon cancer. This variable is in fact associated with an adverse outcome with a reduced risk of death by 20% if patients are affected by a left colon cancer compared to those with right colon cancers. Implications are enormous: for prognosis first but also for follow-up, stratification into clinical trials and treatment (for both medical and surgical therapies). The power of the study is relevant: it enclosed 66 studies with more than 1 million of patients retrospectively or prospectively analyzed for survival according to common variables known to be prognostic in colorectal cancer (age, sex, stage, race, adjuvant CT..etc) in multivariate analysis.
Side is significantly associated with survival independent of other covariates analyzed. The question of the side is old and partially known, but no study systematically explored the published literature to confirm this suggestion. Recent large randomized trials in metastatic disease showed different results according to the site of disease with right colon cancers usually less responsive to anti-EGFR treatment due to a different molecular behavior and conversely left colon cancers which attained the greater benefit from cetuximab and panitumumab due to less BRAF mutations in their tissue. Also, a less extensive and radical lymphadenectomy in right-sided cancers, without a complete mesocolon excision during surgery, could hamper their cure rate, as our colorectal surgeon’s team lead by Prof. Giovanni Sgroi and Luca Turati MD, suggested in the discussion. It is also well known the leads term bias with a later diagnosis of right cancers due to clinical and anatomic reasons.
MedicalResearch.com: What should readers take away from your report?
Response: Side is associated with prognosis in all stages of the disease, but with deeper magnitude in metastatic (stage 4) patients. This means that right colon cancer needs likely a more aggressive strategy in early and advanced disease. Stage 2 tumors could qualify for adjuvant chemotherapy if right-sided, and stage 4 patients (in particular those with BRAF- or RAS-mutated tumors) could attain benefit from triplets with a biologic (e.g., FOLFOXIRI bevacizumab), the most effective scheme tested in randomized trials in this setting.
We will now discuss adjuvant chemotherapy with less anxiety in high risk (right-sided) stage 2 colon cancer patients. No change of attitude instead would probably occur in stage 3, waiting for the final results of de-intensification studies (3 vs 6 months of adjuvant chemotherapy) that could even change our practice in next years (3 months in left colon and 6 months in right colon cancers?).
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Colon cancer as other solid tumors is a heterogeneous disease. In the discussion Gianluca Tomasello MD, from Cremona Hospital discussed the different embryological nature of the 2disease, the microbiota, the immunity-based pathways, and the molecular aberrations that make right and left colon cancers 2 different conditions.
This must be taken into consideration when we treat our patients or when we will enroll them into clinical trials. However, more research is needed to translate it from bench to bedside. Left colon cancer for example that doesn’t present mutation in any of RAS and BRAF gene are exceptionally responsive to chemo + anti-EGFR. This is not the case of right cancers that should be tested for different molecularly driven approaches.
MedicalResearch.com: Is there anything else you would like to add?
Response: A more comprehensive molecular profile with discovering of new targets for systemic therapies are needed in both early and advanced stages. More efficient screening modalities, a skilled operative training for surgeons, more effective therapies with a molecularly-driven based trial design will make right cancer a more curable disease.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Petrelli F, Tomasello G, Borgonovo K, Ghidini M, Turati L, Dallera P, Passalacqua R, Sgroi G, Barni S. Prognostic Survival Associated With Left-Sided vs Right-Sided Colon CancerA Systematic Review and Meta-analysis. JAMA Oncol. Published online October 27, 2016. doi:10.1001/jamaoncol.2016.4227
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