Effective prognostic factors and importance of microsatellite instability in the decision of adjuvant chemotherapy in stage 2-3 colon cancer

Purpose: Colorectal cancers are the 3rd most common malignancy worldwide. Although adjuvant chemotherapy is used as a standard treatment for stage 3 patients, it is not given to all stage 2 patients. Adjuvant chemotherapy is given to patients with high risk factors for stage II colorectal cancer. The most important prognostic factor in colorectal cancer is the stage of the disease. High risk markers in stage II are T4 primary; high grade poorly differentiated histology (signet ring cell, mucinosis tumor), lymphovascular invasion (LVI), perineural invasion (PNI), bowel obstruction and / or perforation closed (including perforation), surgical margin positivity, 12 or less lymph nodes in surgical specimens dissection, high preoperative CEA level (> 5). In addition, microsatellite status is accepted as an important prognostic value used for adjuvant chemotherapy evaluation. In our study, we analyzed the prognostic importance and survival relationships of these risk factors, including microsatellite instability, in patients with colorectal cancer. Method: In this study, 388 patients with early stage (stage 2-3) colorectal cancer who applied to Dicle University Medical Faculty Hospital Oncology Department between 2001-2020 and 58 patients (metastatic and nonmetastatic) whose MS status data were examined were included retrospectively. The data of the patients were accessed via HBYS (Hospital Information Management System). Disease-free survival and overall survival status according to age, gender, stage, pathologically T stage, N stage, grade, lymphovascular-perineural invasion information, tumor location, adjuvant chemotherapy and MSS / MSI (Microsatellite stable / Microsatellite unstable) status analyzed. Results: Of the 388 patients included in the study, 199 (51.3%) were male, 189 (48.7%) were female, 246 (59%) were stage 2 and 142 (42%) were stage 3. In terms of tumor localization, 314 (81.3%) patients were located in the left colon, while 72 (18.7%) patients were located in the right colon. Of these, 186 (48.2%) were located in the rectum, 128 (33.2%) in the sigmoid colon, 46 (11.9%) in the ascending colon, and 26 (6.7%) in the transverse colon. Median disease-free survival of all patients was 91.7 months (64.3-119.2). The median disease-free survival time of stage 2 patients was 135.7 months (107-164.5), and the median disease-free survival time of stage 3 patients was 47 months (27.8-67.3). Median disease-free survival time was statistically higher in stage 2 patients (p < 0.001). While 281 of the patients (78.4%) received adjuvant chemotherapy, 77 (21.5%) of them were not given adjuvant chemotherapy and treatment information of the remaining patients could not be reached. While 166 (72.8%) of stage 2 patients received adjuvant chemotherapy, 62 (27.2%) of them did not receive chemotherapy, while 122 (87.7%) of stage 3 patients received adjuvant chemotherapy treatment, 17 (12.3%) ) the patient did not receive adjuvant chemotherapy. In stage 2 and stage 3 patients, disease-free survival was 111 months in those who received adjuvant chemotherapy, while it was 79 months in those who did not, but there was no statistical significance (p = 0,5). According to the lymphovascular-perineural invasion (LVI-PNI), which is one of the risk factors, the average disease-free survival time of the patients was 54.6 months (30.3-78.9), while the mean disease-free survival time of patients without LVI-PNI was 94.1 months (74.4) -113.8) and it was statistically significant (p = 0.015). When microsatellite (MS) status and disease-free survival data were analyzed, the median disease-free survival time of patients with microsatellite (CNS) stable (CNS) was 39.8 months, while the median disease-free survival time of patients with microsatellite (MSI) instability could not be reached, although statistically the p value has not reached significance yet, there is an expected significance. Median overall survival of all patients was 111.6 months (93.0-130.1). The median overall survival time of stage 2 patients was 134.8 months (120.4-149.1), and the median overall survival time of stage 3 patients was 74.0 months (64.9-83.2). Median overall survival time was found to be statistically higher in stage 2 patients (p <0.001). According to lymphovascular-perineural invasion information obtained from pathology reports, the median overall survival time of patients with LVI-PNI was 48.7 months (43.2-54.1), while the median overall survival of patients without LVIPNI was 108.5 months (47.7) -169.3) and it was statistically significant (p = 0.002). In the MS status and overall survival data analysis, the mean overall survival time of patients with CNS was 43.8 months (34.7-52.9), while the mean overall survival time of patients with MSI was 63.0 months (12.2-113.8), but No statistically significant difference was found (p = 0.513). When the overall survival times of patients who received and did not receive adjuvant chemotherapy were examined, the median overall survival time of patients who received adjuvant chemotherapy was 122.8 months (100.0-145.6), while patients who did not receive adjuvant chemotherapy were 97.0 months (45.0-149.0). There was no clinically significant but statistically significant difference (p = 0.318). When MS status and gender were analyzed, it was MSS in 33 (62.3%) of 53 male patients and MSI in 20 patients (37.7%). MSS was detected in 29 (82.9%) of 35 female patients, while MSI was detected in 6 patients (17.1%) (p = 0.038). Among the pathology data, the MS status of 39 early-stage patients and 29 metastatic patients were analyzed. 25 (64.19%) of the early stage patients were MSS and 14 (35.9%) were MSI. While 24 (82.8%) of metastatic patients were MSS, MSI was detected in 5 patients (17.2%) (p = 0.090). Data of 43 patients were obtained in MS status analysis with grade. While 14 (77.8%) of grade 1 patients were MSS, 4 patients (22.2%) were MSI, while 12 (54.5%) of grade 2 patients were MSS, 10 patients (45.5%) were MSI, while 1 (33.3%) of the grade 3 patients was MSS, 2 patients (66.7%) were MSI (p = 0.175). 66 patients were analyzed for MS status and tumor localization data. Of the 45 left colon tumors, 34 (75.6%) were MSS, while 11 (24.4%) had MSI. Of the 21 right colon tumors, 12 (57.1%) were MSS, while 9 (42.9%) had MSI (p = 0.130). When stage 2 patients were analyzed according to risk factors, the median disease-free survival time of patients without high risk factors was 161.1 months (105.5-216.7), while the median disease-free survival time of patients with high risk factors was 38.6 months (25.6- 51). , 7), and a statistically significant difference was found (p = 0.002). The median overall survival time of patients without high risk factors for overall survival was 161.1 months (146.7-175.5), while the median overall survival time for patients with high risk factors was 77.9 months (20.8-135.8), and There was a statistically significant difference (p = 0.003). When the effect of lymphovascular-perineural invasion and adjuvant chemotherapy status on disease-free survival was examined in stage 2 patients, the mean disease-free survival time of patients with lymphovascular-perineural invasion who received adjuvant chemotherapy was 53.3 months (13.8-92.8), while patients who did not receive adjuvant chemotherapy The average disease-free survival time was 22.2 months (3.7-40.0). Among patients without lymphovascular-perineural invasion, the mean overall survival time of patients who received adjuvant chemotherapy was 100.5 months (76.3-124.8), while the mean disease-free survival time of patients not receiving adjuvant chemotherapy was 115.9 months (96.5-135.3). was calculated and a statistically significant difference was found (p = 0.001). Conclusion: In our study, disease-free and overall survival was longer in stage 2 patients compared to stage 3 patients. The overall survival of patients who received adjuvant chemotherapy was longer than those who did not receive chemotherapy, and had clinical significance. In our study, it has been shown that lymphovacular and perineural invasion are prognostic factors in Stage 2 patients, and their presence causes shorter survival times. In addition, adjuvant chemotherapy in stage 2 patients with high risk group with LVI-PNI prolonged both disease-free and overall survival. In terms of the effect of MSI status on survival, the median disease-free survival time has not been reached yet, and there is a statistically expected significance.