Node-positive Colon Cancer Research Articles

Outcomes of Elderly Patients with Node-Positive Colon Cancer. A Multi-Center Population-Based Cohort Study

BackgroundIn this large population-based cohort study, we examined the prognostic significance of various clinical, pathological, and contextual variables for their correlation with survival in elderly patients with stage III colon cancer. MethodsPatients aged ≥70 years with stage III colon cancer, diagnosed in Saskatchewan during 2012–2018, were evaluated. A Cox proportional multivariate survival analysis was performed to determine factors correlated with overall survival and disease-free survival. Results404 patients with a median age of 79 years and a male-to-female ratio of 1:1 were identified. Among them, 48% were aged ≥80 years, 66% had ≥1 major comorbid illness, 46% had high-risk disease, and 50% had a node-positive to node-harvested (NPNH) ratio of >0.1. Forty-three percent of patients received adjuvant chemotherapy. The 5-year disease-free survival with chemotherapy was 49% vs. 30% without chemotherapy (p < 0.001). The 5-year overall survival with adjuvant chemotherapy was 64% vs. 49% without chemotherapy (p < 0.001). On multivariate analysis a past history of cancer, hazard ratio (HR): 1.47 (95%CI: 1.12–1.94); presence of an ostomy, HR: 1.53 (1.16–2.03); NPNH ratio > 0.1, HR: 1.51 (1.15–1.98); grade III tumor, HR: 1.54 (1.16–2.04); WHO performance status > 1, HR: 1.42 (1.06–1.90); no adjuvant chemotherapy, HR: 1.82 (1.32–2.50); high-risk stage III disease, HR: 1.60 (1.22–2.11), and baseline CEA > 5, HR: 1.98 (1.50–2.61) were independently correlated with OS. ConclusionsThis study highlights the prognostic importance of several factors in elderly patients with stage III colon cancer, particularly the benefit of adjuvant chemotherapy on survival. Key predictors of poorer overall survival include a past history of cancer, presence pf an ostomy, and a higher NPNH ratio. These findings emphasize the need for personalized treatment approaches to improve outcomes in this vulnerable population. Mico-AbstractThis population-based cohort study evaluated 404 elderly patients with stage III colon cancer in Saskatchewan from 2012 to 2018. Multivariate analysis identified a past history of cancer, presence of an ostomy, high-risk disease, high node-positive-to-node-harvested ratio, high-grade cancer, low performacne status and no adjuvant chemotherapy, all correlated with inferior outcomes. These findings emphasize the benefit of chemotherapy and the importance of personalized care for this vulnerable population.

The prognostic and predictive significance of perineural invasion in stage I to III colon cancer: a propensity score matching-based analysis

BackgroundColorectal cancer (CRC) presents with varying prognoses, and identifying factors for predicting metastasis and outcomes is crucial. Perineural invasion (PNI) is a debated prognostic factor for CRC, particularly in stage I-III patients, but its role in guiding adjuvant chemotherapy for node-positive colon cancer remains uncertain.MethodsWe conducted a single-center study using data from the Colorectal Section Tumor Registry Database at Chang Gung Memorial Hospital, Taiwan. This prospective study involved 3,327 CRC patients, 1,536 of whom were eligible after application of the exclusion criteria, to investigate the prognostic value of PNI in stage I-III patients and its predictive value for node-positive/negative cancer patients receiving adjuvant chemotherapy. Propensity score matching (PSM) was used to minimize selection bias, and follow-up was performed with standardized procedures.ResultsPNI-positive (PNI+) tumors were associated with higher preoperative CEA levels and more frequent adjuvant chemotherapy. After PSM, PNI + tumors were associated with marginally significantly lower 5-year disease-free survival (DFS) and significantly lower overall survival (OS) rates in stages III CRC. However, no significant differences were observed in stages I and II. Subgroup analysis showed that among PNI + tumors, only poorly differentiated tumors had higher odds of recurrence. PNI did not predict outcomes in node-negative colon cancer. Adjuvant chemotherapy benefited PNI + patients with node-positive but not those with node-negative disease.ConclusionsOur study indicates that PNI is an independent poor prognostic factor in stage III colon cancer but does not predict outcomes in node-negative disease. Given the potential adverse effects of adjuvant chemotherapy, our findings discourage its use in node-negative colon cancer when PNI is present.

Outcomes of elderly patients with node-positive colon cancer: A multi-center population-based cohort study.

33 Background: Patients with stage III colon cancer are at high risk of recurrent disease. In this large population based cohort study we examined prognostic significance of chemotherapy and other clinical, pathological &amp; contextual variables that are associated with inferior outcomes in elderly patients with stage III colon cancer. Methods: Patients ≥ 70 years with stage III colon cancer diagnosed in Saskatchewan, a Canadian province, and underwent resection of the primary tumor during 2012-2018 were evaluated. A Cox proportional multivariate survival analysis was performed to determine factors correlated with overall survival (OS) and disease-free survival (DFS). Results: 404 eligible patients with median age of 79 yrs &amp; M:F of 1:1 were identified. 48% were ≥80 years, 60% were rural resident, 66% had ≥ 1 major comorbid illness, 34% had WHO performance status &gt;1, 14% has an ostomy formation, 46% had a T4 or N2 high-risk disease, and 50% had node positive to node harvested (NPNH) ratio of &gt;0.1. 43% patients received adjuvant chemotherapy. Median time to start chemo was 9 weeks. Patients who did not receive adjuvant chemotherapy were significantly older, had low performance status or experienced high rate of post-operative complications, high serum creatinine, low albumin, anemia, elevated WBC count and platelets. Median OS of all patients was 51 months (95%CI: 42.4-59.6), with estimated 5 &amp; 10-yr OS of 45% and 30%. Median DFS of entire cohort was 32 months (26.3-37.7) with 5 &amp; 10-yr DFS of 34% and 20%. Patients who received adjuvant chemotherapy had median OS of 106 months (83.8-128.5) vs. 30 months (23.4-36.6), p&lt;0.001 with 5 &amp; 10-yr OS of 64% and 49% vs. 31% and 19% (p&lt;0.001). Patients who received adjuvant chemotherapy had median DFS of 56 months (28.2-83.9) vs. 22 months (16.5-27.5), p&lt;0.001 with 5 &amp; 10-yr DFS of was 49% and 30% vs. 24% and 13% (p=&lt;0.001). The Cox-multivariate analysis revealed a past history of cancer, HR, 1.32 (1.03-1.72); ostomy, HR, 1.33 (1.02-1.74); NPNH ratio &gt;0.1, 1.34 (1.04-1.78); grade III tumor, 1.36 (1.04-1.78); WHO performance status &gt;1, HR, 1.38 (1.05-1.82); no adjuvant chemo, HR, 1.38 (1.03-1.85); high-risk stage III disease, HR, 1.39 (1.10-1.79), and baseline CEA &gt;5, HR, 1.75 (1.34-2.29), were independently correlated with DFS whereas past history of cancer, HR, 1.47 (1.12-1.94); ostomy, HR, 1.53 (1.16-2.03); NPNH ratio &gt;0.1, 1.51 (1.15-1.98); grade III tumor, 1.54 (1.16-2.04); WHO performance status &gt;1, HR, 1.42 (1.06-1.90); no adjuvant chemo, HR, 1.82 (1.32-2.50); high-risk stage III disease, HR, 1.60 (1.22-2.11), and CEA &gt;5, HR, 1.98 (1.50-2.61) were independently correlated with OS. Conclusions: In elderly patients with stage III colon cancer lack of adjuvant chemotherapy, poor performance status, T4 or N2 disease, grade III tumor, elevated baseline CEA, past history of a secondary cancer, elevate NPNH ratio &gt;0.1 and an ostomy formation correlate with inferior outcomes.

Higher Numbers of Examined Lymph Nodes Are Associated with Increased Survival in Resected, Treatment-Naïve, Node-Positive Esophageal, Gastric, Pancreatic, and Colon Cancers

Background or PurposeThe role of extended lymphadenectomy as part of resection for lymph node (LN)–positive gastrointestinal (GI) malignancies remains controversial with no clear clinical guidance. The purpose of this retrospective study is to determine whether the number of LNs examined as part of GI malignancy resections affects overall survival (OS) among patients with node-positive esophageal, gastric, pancreatic, and colon cancers. MethodsParticipants with LN-positive GI cancers who were diagnosed between 2004 and 2015 and underwent oncologic resections were selected from National Cancer Database (NCDB). The primary predictor was the number of examined LNs categorized in tertiles. The effect on OS was measured by hazard ratio (HR) derived from multivariate Cox regression analyses. ResultsFrom 2004 to 2015, 1877, 10,086, 18,193, and 102,500 patients with LN-positive esophageal, gastric, pancreatic, and colon adenocarcinomas who did not receive neoadjuvant treatment and underwent oncologic tumor resection were registered in the NCDB. Using multivariate Cox proportional hazard modeling, greater LNs examined in surgically resected LN-positive GI cancers were found to be associated with increased OS for all histologies. This association was the strongest (as compared to the lowest tertile) for gastric cancer (middle tertile: HR = 0.91, 95% CI, 0.86–0.96, p = 0.001; highest tertile: HR = 0.73, 95% CI, 0.69–0.78, p < 0.001), followed by colon (highest tertile: HR = 0.86, 95% CI, 0.84–0.88, p < 0.001), esophageal (highest tertile: HR = 0.83, 95% CI, 0.72–0.95, p = 0.01), and pancreatic (highest tertile: HR = 0.93, 95% CI, 0.89–0.98, p = 0.002) cancers. Discussion and ConclusionIn patients with surgically resected node-positive GI malignancies who did not receive neoadjuvant systemic therapy, a higher number of examined LNs is associated with increased OS. This association is the strongest for gastric cancer, followed by colon, esophageal, and pancreatic cancers respectively.

The Negative Prognostic Impact of Lymph Node Skip Metastasis in Stage III Colon Cancer With pN1 Disease: A Single Center and Retrospective Cohort Study.

Lymph node skip metastasis is a subgroup of lymph node metastatic patterns with low incidence in node-positive colon cancer. Its clinical significance is still unclear. This study aimed to investigate the prognostic impact of lymph node skip metastasis in stage III colon cancer. Retrospective observational analysis. The study was conducted at Taipei Veterans General Hospital. Patients with stage III colon cancer who underwent D3 lymphadenectomy between 2006 and 2015. The patients were divided into a lymph node skip metastasis positive group and a negative group. Recurrence-free survival and overall survival were compared using Kaplan-Meier curves and log-rank test. Cox regression was applied to identify related risk factors influencing survival. A total of 461 patients were reviewed, and lymph node skip metastasis positive patients represented 13.2% of our sample. Patients with lymph node skip metastasis tended to present with a higher proportion of right sided cancer, lower positive lymph nodes, lower lymph node ratio and higher mean BMI. Liver recurrence was more prevalent in the lymph node skip metastasis group ( p = 0.028) than in the negative group. The presence of lymph node skip metastasis was a negative prognostic factor for 5-year recurrence-free survival (51.4% vs. 68.7%, p = 0.002) and 5-year overall survival (66.4% vs. 80.4%, p = 0.024) in Kaplan-Meier curves and multivariate Cox regression. Subgroup analysis revealed the survival significance of recurrence-free survival ( p = 0.001) and overall survival ( p = 0.011) in lymph node skip metastasis with pN1 disease. Retrospective design, single center nature, and sampling error. Lymph node skip metastasis is an independent negative prognostic factor in stage III colon cancer with pN1 disease. More intensive surveillance may be necessary for patients of this subgroup. See Video Abstract at http://links.lww.com/DCR/C60.

The Impact of Metastatic Lymph Node Size on Long-term Outcomes for pStage III Colon Cancer.

To clarify the impact of metastatic lymph node size on long-term outcomes in patients undergoing curative colectomy for pathological stage III colon cancer. This study enrolled patients who underwent curative colectomy for pStage III colon cancer between January 2013 and December 2015. All patients were divided into four groups based on the short-axis diameter of the largest MLN: Group A, <5 mm; Group B, ≥5 mm and <10 mm; Group C, ≥10 mm and <15 mm; Group D, ≥15 mm. A total of 209 patients were analyzed. The 5-year recurrence-free survival rates of Groups A, B, C, and D were 82.3%, 74.6%, 74.5% and 60.7%, respectively. In multivariate analysis, Group D (hazard ratio=3.95; 95% confidence interval, 1.34-11.65; p=0.01) was independently associated with worse RFS. Bulky MLNs might be a poor prognostic factor in node-positive colon cancer.

Combining tumor deposits with the number of lymph node metastases to improve the prognostic accuracy in stage III colon cancer: a post hoc analysis of the CALGB/SWOG 80702 phase III study (Alliance)☆

In colon cancer, tumor deposits (TD) are considered in assigning prognosis and staging only in the absence of lymph node metastasis (i.e. stage III pN1c tumors). We aimed to evaluate the prognostic value of the presence and the number of TD in patients with stage III, node-positive colon cancer. All participants from the CALGB/SWOG 80702 phase III trial were included in this post hoc analysis. Pathology reports were reviewed for the presence and the number of TD, lymphovascular and perineural invasion. Associations with disease-free survival (DFS) and overall survival (OS) were evaluated by multivariable Cox models adjusting for sex, treatment arm, T-stage, N-stage, lymphovascular invasion, perineural invasion and lymph node ratio. Overall, 2028 patients were included with 524 (26%) TD-positive and 1504 (74%) TD-negative tumors. Of the TD-positive patients, 80 (15.4%) were node negative (i.e. pN1c), 239 (46.1%) were pN1a/b (<4 positive lymph nodes) and 200 (38.5%) were pN2 (≥4 positive lymph nodes). The presence of TD was associated with poorer DFS [adjusted hazard ratio (aHR)= 1.63, 95% CI 1.33-1.98] and OS (aHR= 1.59, 95% CI 1.24-2.04). The negative effect of TD was observed for both pN1a/b and pN2 groups. Among TD-positive patients, the number of TD had a linear negative effect on DFS and OS. Combining TD and the number of lymph node metastases, 104 of 1470 (7.1%) pN1 patients were re-staged as pN2, with worse outcomes than patients confirmed as pN1 (3-year DFS rate: 65.4% versus 80.5%, P= 0.0003; 5-year OS rate: 87.9% versus 69.1%, P= <0.0001). DFS was not different between patients re-staged as pN2 and those initially staged as pN2 (3-year DFS rate: 65.4% versus 62.3%, P= 0.4895). Combining the number of TD and the number of lymph node metastases improved the prognostication accuracy of tumor-node-metastasis (TNM) staging.

P-118 Survival outcomes of adjuvant chemotherapy in stage IVA/B high-grade appendiceal cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Despite the lack of supporting data, it is a common practice to use adjuvant chemotherapy (ACT) in high-grade appendiceal cancer patients with peritoneal metastases (stage IVA/B) after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Low incidence precludes conducting randomized clinical trials; therefore, many oncologists extrapolate from node-positive colon cancer studies demonstrating benefits of ACT. We aimed to evaluate ACT efficacy after CRS/HIPEC in patients with stage IVA/B appendiceal cancer. A single-institution retrospective cohort study using a prospective database was conducted. Stage IVA/B high-grade appendiceal cancer patients who underwent CRS/HIPEC with CC-0/1/2 were included. Survival outcomes were compared between patients receiving ACT and those under observation. Subgroup analysis was performed based on histopathologic subtype, neoadjuvant chemotherapy (NACT), lymph node (LN) status, and peritoneal cancer index (PCI) ≥20. We identified 196 patients: 84 with ACT and 112 with no adjuvant chemotherapy (NoCT). There was no significant difference between groups in age, preoperative tumor markers, NACT frequency, PCI, as well as complete cytoreduction (CC-0/1) and postoperative major complication rates. ACT group had more patients with signet ring cell carcinoma (SRC) (51% vs 31%, p=0.022) and positive LN (56% vs 34%, p=0.002). ACT regimens included 5-FU/capecitabine in 11 (13%), FOLFOX in 53 (63%), FOLFIRI in 17 (20%), with/without bevacizumab. Regimens were unknown in 3 (4%) patients. Median number of cycles was 8 (IQR: 4-12) and median time between CRS/HIPEC and ACT was 12 (IQR: 8-15) weeks. Median follow-up was 68 months. Overall survival (OS) did not significantly differ between groups (54 months in ACT vs 66 in NoCT, p=0.894). Subgroup analysis showed no OS benefit of ACT compared to NoCT for patients with NACT (median OS: 40 vs 33 months, p=0.284) or without NACT (53 vs 82 months, p=0.457), with SRC (39 vs 33 months, p=0.389) or without SRC (54 vs 89 months, p=0.583), positive LNs (39 vs 33 months, p=0.894), or PCI ≥20 (39 vs 24 months, p=0.356), respectively. Additionally, ACT did not impact OS after adjusting for other factors in the multivariable Cox regression model. In our patient cohort, colorectal-type ACT did not improve OS in stage IVA/B appendiceal cancer treated with CRS/HIPEC, even when adjusting for confounding factors. This may be due to differences in tumor biology compared to colon cancer or the inability to detect differences in a small sample size. Data from prospective collaborative clinical trials are needed.

Adherence to clinical practice guidelines for adjuvant chemotherapy for colorectal cancer in Uruguay: A population-based study.

53 Background: Despite surgery, the 5-year risk of systemic recurrence of colorectal cancer (CRC) in the absence of any further therapy is approximately 50 % for those with lymph node involvement and 20 ─ 30 % if the lymph nodes are negative. Adjuvant chemotherapy contributes to improved disease-free and overall survival for node-positive (stage III) or high-risk node negative (stage IIB) colon cancer. Similar benefits are observed for adjuvant chemoradiotherapy in rectal cancer. Previous research shows varied rates of adherence to published adjuvant chemotherapy Clinical Practice Guidelines (CPGs) for CRC, although population-based data is scarce. Purpose: The aim of this analysis was to assess adherence rates to adjuvant chemotherapy prescription within 16 weeks of surgery according to local and international CPGs for CRC patients treated with curative intent between 2008 and 2019 at the Uruguayan National Cancer Institute. Data regarding factors associated with chemotherapy receipt beyond 16 weeks from surgery and chemotherapy non receipt was also retrieved and analysed. Methods: We retrospectively reviewed medical and pathology reports of 833 patients diagnosed with CRC at our institution. Patients with stages IIB or III CRC who underwent curative-intent surgery were identified and included in the present analysis. A 16-week benchmark timeline for treatment initiation from date of surgery was considered. Fisher’s exact test was used to determine factors independently associated with receipt of chemotherapy and meeting the 16-week benchmark (p 0.05). Results: A total of 400 patients were identified of which 72% had peritoneal colorectal tumors and 28% had sub-peritoneal rectal tumors. Approximately 70% of the latter group received neoadjuvant chemo-radiotherapy. Considering the total cohort, 61% received adjuvant chemotherapy. Factors predicting chemotherapy receipt in the peritoneal colorectal group were age ≤ 70 and stage III disease. In the sub-peritoneal rectal group no significant effect was found. The 16-week benchmark was met in 72% (175) of those receiving chemotherapy and 70.6% (167) completed 6 months of systemic adjuvant treatment. A total of 156 patients (39%) did not receive adjuvant chemotherapy. The factors predicting chemotherapy non receipt were age &gt; 70 and stage IIB in the peritoneal colorectal group. Conclusions: This analysis of adherence to CPGs identified several factors associated with chemotherapy non receipt and chemotherapy receipt outside of timeline benchmarks from date of curative-intent surgery in Montevideo, Uruguay. The two main factors significantly associated with chemotherapy non receipt were advanced age and lower disease stage. To our knowledge, our data is the first to elucidate these specific factors in the Uruguayan CRC patient population.

Tumour size and overall survival among surgically treated patients with non-metastatic colon cancer in the U.S. Military Health System.

Larger tumour size and lymph node involvement traditionally predict poorer survival in colon cancer patients. However, it has been recently suggested that very small tumours (<5mm) may be a predictor of poor prognosis in colon cancer patients when lymph nodes are involved. This study investigated whether node-positive colon cancer patients with small tumours had worse survival compared to those with larger tumours in the Department of Defense's (DoD) Military Health System (MHS), a universal health care system. Surgically treated colon cancer patients were identified from the DoD's Automated Central Tumour Registry (ACTUR). These patients were diagnosed with Stage I-III colon cancer between 1989 and 2010, had one or more lymph nodes examined, did not receive pre-operative radiotherapy and were followed through 2013 to determine vital status. Multivariable Cox models were used to examine survival differences according to tumour size, and data were stratified by lymph node status and age. There were no differences in overall survival according to tumour size in the study population. These findings remained similar in analyses stratified by lymph node status and age. In a universal healthcare system, small tumour size is not associated with worse prognosis in node-positive colon cancer patients.

The Prognostic Significance of Lymph Node Status and Lymph Node Ratio (LNR) on Survival of Right Colon Cancer Patients: a Tertiary Center Experience.

Colon cancer is a major health problem and is one of the most frequent cancers all over the world. In Egypt, the incidence of colon cancer is relatively low, but its mortality rate is high. Lymphatic spread of colon cancer is one of the most important factors affecting the prognosis of patients. Recently, the lymph node ratio (LNR) has been evaluated as a prognostic parameter for survival. This study aimed at evaluation of nodal status of resected specimens and LNR, as well as its impact on the disease-free survival (DFS) and overall survival (OS) after curative resection of right colon cancer. The institutional registry of the Oncology Center Mansoura University (OCMU) was revised for node-positive right colon cancer cases that were operated in the period between January 2010 and January 2015. Fifty-three patients met the inclusion criteria and were followed up till January 2020. A total of 766 lymph nodes were excised from the patients. Thirty-two patients (60.4%) had a LN yield of ≥12 LNs with a mean LNR of 0.257 ± 0.27. Multivariate analysis of outcomes showed that LNR was significantly correlated with both DFS (p = 0.015) and OS (p = 0.024). Moreover, the number of resected LNs was also associated with statistically significant relationship with the DFS and OS. Our study confirms the validity of LNR as a prognostic tool that correlates with the survival of patients. Moreover, LNR cutoff values may help predict those of high chance of tumor recurrence. MS/20.03.1087 (Institutional IRB), date of registration: March 10, 2020, "retrospectively registered".

The prognostic effect of adjuvant chemotherapy in the colon cancer patients with solitary lymph node metastasis

PurposePrevious studies have reported paradoxical survival prognoses for some node-negative and node-positive colon cancer patients. However, current guidelines recommend adjuvant chemotherapy (CT) only for node-positive patients. This study investigated the efficacy of adjuvant CT for patients who underwent radical surgery for colon cancer with solitary lymph node (LN) metastasis.MethodsThis study included 281 patients treated between 2004 and 2015. Patients were classified into no-CT (n = 39) and CT (n = 242) groups, and the survival outcomes and recurrence-related follow-up data were analyzed.ResultsThe groups exhibited similarities in tumor sidedness, tumor differentiation, and pathologic stage. However, the age, ASA class, and preoperative CEA level were relatively lower in the CT group. Although the CT group had a higher 5-year overall survival (OS) rate than the no-CT group (88.4% vs. 65.3%, p < 0.001), the groups did not differ in terms of 5-year disease-free survival (DFS) (CT, 84.1% vs. no-CT, 83.3%, p = 0.490). A multivariate analysis identified adjuvant CT as an independent factor for OS but not for DFS. A highly examined LN count (≥ 12) was associated with improved DFS improvement. However, D3 LN dissection was not associated with DFS or OS. For DFS, intermediate/apical positive LNs received a high hazard ratio relative to pericolic/epicolic LNs (2.080, 95% confidence interval: 0.979–4.416), but this was not significant (p = 0.057).ConclusionsAdjuvant chemotherapy did not provide clear advantages for colon cancer with solitary LN metastasis. Further large studies that analyze several prognostic factors are needed to establish tailored adjuvant CT administration guidelines.

Neoadjuvante, adjuvante und palliative onkologische Therapie beim kolorektalen Karzinom

Neoadjuvant, adjuvant and palliative systemic therapy of colorectal cancer Abstract. Neoadjuvant therapy is indicated for stage T3 / 4 and all N1 rectal cancers. Usually, chemoradiotherapy with capecitabine or 5FU is applied within a timeframe of 5 ½ weeks. 6 to 9 weeks later surgery is performed. The aim of neoadjuvant chemoradiotherapy is resectability and a low local recurrence rate. After surgery with curative intent, adjuvant chemotherapy increases the cure rate by 20 % in node-positive (stage III) colon cancer. For most patients, 3 months of capecitabine / oxaliplatin are adequate. For high risk patients, 6 months of therapy are necessary if a Folfox regimen is used. In the palliative setting, understanding the biology of the tumor is the key to systemic therapy. Next generation sequencing of tumor DNA is mandatory. Mismatch repair proficient tumors benefit from dual chemotherapy in combination with an antibody. Median survival increases from 6 to 30 months through palliative chemotherapy. Mismatch repair deficient tumors are in need of immunotherapy. Long lasting remission have been observed in this population.

Lymph node ratio is inferior to pN-stage in predicting outcome in colon cancer patients with high numbers of analyzed lymph nodes

BackgroundThe lymph node ratio (LNR), i.e. the number of positive lymph nodes (LN) divided by the total number of analyzed LN, has been described as a strong outcome predictor in node-positive colon cancer patients. However, most published analyses are constrained by relatively low numbers of analyzed LN. Therefore, the objective of the present study was to evaluate the prognostic impact of LNR in colon cancer patients with high numbers of analyzed LN.MethodsOne hundred sixty-six colon cancer patients underwent open colon resection. All node-positive patients were analyzed for this study. The number of analyzed LN, of positive LN, the disease-free (DFS) and overall survival (OS) time were prospectively recorded. Patients were dichotomously allocated to a high or a low LNR-group, respectively, with the median LNR (0.125) as a cut-off value. Median follow-up was 34.3 months.ResultsFifty-eight patients (34.9%) were node-positive. The median number of analyzed LN was 23 (range 8–54). DFS and OS were significantly shorter in pN2 vs pN1 patients (p < 0.001, and p = 0.001, respectively), and in LNR high vs low patients (p = 0.032, and p = 0.034, respectively). pN2 (vs pN1) disease showed hazard ratios (HR) of 6.2 (p < 0.001), and 6.8 (p < 0.005; for DFS and OS, respectively), while LNR high (vs low) showed HR of 3.0 (p =0.041), and 4.5 (p = 0.054).ConclusionsLNR is a reasonable outcome predictor in node-positive colon cancer patients. However, LNR is inferior to pN-stage in predicting survival in patients with high number of harvested lymph nodes.

The prognostic significance of lymph node size in node-positive colon cancer.

ObjectivesTo (i) show the outcome benefits of enlarged lymph nodes in node-positive colon cancer cases, as it was shown previously in negative node cases; (ii) disprove the stage migration theory and (iii) list the factors affecting lymph node size and yield.MethodsA retrospective study including 234 node-positive colon cancer cases was scheduled and performed. All recovered lymph nodes (6969) from 234 cases were microscopically examined in regard to (a) lymph node size (b) presence of metastasis (c) extent of intra-nodal metastasis. On the basis of resulting data, a statistical analysis was performed.ResultsMetastases occurred in all size categories, though more often in larger lymph nodes. Fifty-one percent of all metastasised nodes were 2 to 6 mm in size. Approximately half of all nodes >10 mm were microscopically free of cancer. Cases with a small lymph node metastasis to lymph node size ratio (MSR) had a better prognosis than others: 85 months (95% CI: 72–97) vs. 67 months (95% CI: 47–88), p <0.001 (mean, overall survival). To differentiate between cases with the same ratio but different absolute lymph nodes sizes, we divided the cases into two groups that differed in their number of moderate to large lymph nodes. The group with more moderate to large lymph nodes showed a clear outcome benefit: 104 months (95% CI: 86–122) vs. 66 months (95% CI: 54–77), p = 0.014 (mean, overall survival).ConclusionsMetastasised lymph nodes affect all size categories, and large lymph nodes are not always metastasised. The combination of enlarged lymph nodes and a small lymph node metastasis to lymph node size ratio (MSR) is associated with a better prognosis than others. When enlarged lymph nodes were considered as surrogate markers of an effective local immune response due to nodal hyperplasia, the immune system could be seen as the confounder affecting both lymph node size and prognosis. Our results are pointing in this direction and, along with other reasons, are challenging the stage migration theory.

Prognostic significance of number versus location of positive mesenteric nodes in node positive colon cancer.

3587Background: Metastasis to locoregional lymph nodes (LN) is one of the most powerful predictors of recurrence free survival (RFS) in colon cancer (CC). Debate persists on the prognostic value of...

Prognostic value of total number of lymph nodes retrieved differs between left-sided colon cancer and right-sided colon cancer in stage III patients with colon cancer

BackgroundThe consensus is that a minimum of 12 lymph nodes should be analyzed at colectomy for colon cancer. However, right colon cancer and left colon cancer have different characteristics, and this threshold value for total number of lymph nodes retrieved may not be universally applicable.MethodsThe data of 63,243 patients with colon cancer treated between 2004 and 2012 were retrieved from the National Cancer Institute’s Surveillance, Epidemiology, and End Results database. Multivariate Cox regression analysis was used to determine the predictive value of total number of lymph nodes for survival after adjusting for lymph nodes ratio. The predictive value in left-sided colon cancer and right-sided colon cancer was compared. The optimal total number of lymph nodes cutoff value for prediction of overall survival was identified using the online tool Cutoff Finder. Survival of patients with high total number of lymph nodes (≥12) and low total number of lymph nodes (< 12) was compared by Kaplan–Meier analysis.ResultsAfter stratifying by lymph nodes ratio status, total number of lymph nodes≥12 remained an independent predictor of survival in the whole cohort and in right-sided colon cancer, but not in left-sided colon cancer. The optimal cutoff value for total number of lymph nodes was determined to be 11. Low total number of lymph nodes (< 11) was associated with significantly poorer survival after adjusting for lymph nodes ratio in all subgroups except in the subgroup with high lymph nodes ratio (0.5–1.0).ConclusionsPrevious reports of the prognostic significance of total number of lymph nodes on node-positive colon cancer were confounded by lymph nodes ratio. The 12-node standard for total number of lymph nodes may not be equally applicable in right-sided colon cancer and left-sided colon cancer.

The Prognostic Significance of the Metastatic Lymph Node Ratio versus the Number of Affected Lymph Nodes in Patients with Colorectal Cancer Stage III Undergoing Potentially Curative Surgery

AbstractBackground: Many investigators have questioned the prognostic power of the TNM system in the prognosis of colorectal cancer because of the possibility of stage migration, and have proposed alternative prognostic methods; one of those is the lymph node ratio.Aim of Work: The objective of this study is to compare the prognostic significance of the LNR with the absolute number of affected lymph nodes for resected colorectal ade-nocarcinoma stage III regarding overall and disease specific survival.Patients and Methods: 55 patients with colorectal cancer stage III who underwent curative surgery were enrolled in a retrospective cohort study reviewing their medical charts from Medical Oncology Department between January 2005 and December 2006, and their five years follow-up period regarding local recurrence, metastasis and survival.Results: The mean follow-up time was 55.1±18 months (range 6-72, median 60 months). During this time period, 12 (21.8%) patients died of disease, 20 (36.4%) patients developed local recurrence or metastasis. Overall Survival (OS) was 90.9%, 85.5%, 78.2% at 1.5, 3, 5 years respectively. Disease Specific Survival (DSS) was 90.9%, 74.5%, 63.6% at 1.5, 3, 5 years respectively.Five year overall survival rates was significantly worse in colorectal cancers with LNR >40% (p-value 4 showed significant worsening in the 5 year DSS only (p-value <0.05, hazard ratio 2.8, 95% CI 1.025-7.7) vs. (p-value <0.05, hazard ratio 0.32, 95% CI 0.13-0.8) respectively.Conclusion: LNR was a robust prognostic indicator for node-positive colon cancers undergoing curative surgery. Because this ratio-based staging was demonstrated to reduce stage migration and to aid in identifying high-risk patients, application of the pLNR improved patient stratification in colorectal cancer and may be considered in future staging systems, it could be proposed as a standard tool for colon cancer staging.

Comparison of two novel staging systems with the TNM system in predicting stage III colon cancer survival

Adaptations of the TNM staging system that incorporate the Lymph Node Ratio (LNR) have been proposed for stage III colon cancer. This study compared the concordance of two novel staging systems and the TNM system with observed survival outcomes in stage III patients. A review of patients who underwent surgery for stage III colon cancer between January 2002 and April 2015 at a tertiary care centre was performed. The Kaplan-Meier method was used to estimate the 5-year overall (OS) and disease free survival (DFS) rates, and the concordance probability was calculated to evaluate the discriminatory power of the staging systems. Two hundred and sixty-one patients were identified. For TNM stages IIIA, IIIB, and IIIC, 5-year OS was 83.4%, 67.6%, and 38.3%, respectively (P < 0.001). All three staging systems were independently predictive of OS and DFS (P < 0.001). However, the novel staging system by Sugimoto et al18 was the most favourable prognostic tool, with a concordance of 0.646 for DFS and 0.659 for OS. The novel staging system by Sugimoto et al18 was superior to the TNM system. Incorporating LNR into staging models for node positive colon cancers may improve survival information available to patients and potentially aid treatment decisions.

Revisiting Dukes' paradigm; some node positive colon cancer patients have better prognosis than some node negative patients.

The current study tried to evaluate the prognostic value of a modified staging system compared to the American Joint Committee on Cancer (AJCC) staging system for patients with colon cancer. Surveillance, epidemiology and end results (SEER) database (2004-2014) was queried through SEER*Stat program and AJCC 7th stages were constructed. Through recursive partitioning analysis and subsequent decision tree formation, suggested new stages were formulated based on T and N descriptors. Overall survival analyses were performed through Kaplan-Meier analysis. The cancer-specific Cox regression hazard (adjusted for age, gender, sub-site, grade, race and surgery) was calculated and pair wise comparisons of hazard ratios were conducted. A total of 159,683 non-metastatic patients with colon cancer were recruited in the analysis. Pair wise hazard ratio comparisons among different AJCC 7th stages were conducted and all comparisons were significant (P<0.0001). However, it should be noted that the adjusted risk of death among stage IIC patients was higher than stage IIIA and IIIB. Pair wise hazard ratio comparisons among different modified system stages were also conducted and all comparisons were significant (P<0.0001). The outcomes of survival analysis were the same regardless of the number of examined lymph nodes (<12 vs.≥12). Concordance index (using death from colon cancer as the dependent variable) for AJCC 6th staging system was 0.704 (SE 0.002; 95% CI 0.701-0.708); for AJCC 7th staging system was 0.708 (SE 0.002; 95% CI 0.704-0.711); for Dukes staging system was 0.670 (SE 0.002; 95% CI 0.666-0.674); and for modified staging system was 0.712 (SE 0.002; 95% CI 0.709-0.716). The proposed modified staging system provided an improved prognostication for colon cancer patients (particularly for stage II/III disease) compared to AJCC staging system. Further external validation of the proposed staging system is needed before adoption into routine practice.