IIIA Colon Cancer Research Articles

Staging Paradox and recurrence pattern among stage IIB, IIC, and IIIA Colon cancers: a retrospective cohort study

PurposeThe survival rates of patients with stage IIB and IIC colon cancer are paradoxically inferior to that of patients with stage IIIA colon cancer. This study aimed to examine the oncological outcomes and investigate the factors that could affect the staging paradox among stage IIB, IIC, and IIIA colon cancers based on a 9-year cancer database.MethodsPatients with stage IIB (pT4aN0M0), IIC (pT4bN0M0), or IIIA (pT1-2N1M0) colon cancer were retrospectively selected from a prospectively maintained medical database from January 2011 to December 2019. Factors that might influence the staging paradox, including radicality, harvested lymph nodes, and chemotherapy administration, were examined.ResultsA total of 282 patients (stage IIB, n = 59; stage IIC, n = 46; and stage IIIA, n = 177) were enrolled. Patients with stage IIB/C cancer demonstrated higher carcinoembryonic antigen levels, larger tumor size, more frequent tumor obstruction, and higher locoregional recurrence than those with stage IIIA cancer. With respect to 10-year locoregional recurrence-free survival and cancer-specific survival, patients with stage IIB and IIC cancers had significantly lower survival rates than did those with stage IIIA cancer (73.7% vs. 66.3% vs. 91.2%, P = 0.0003; 5.4% vs. 10.9% vs. 11.2%, P = 0.0023). The staging paradox persisted in patients who underwent R0 resection, had harvested lymph nodes ≥ 12, and received chemotherapy, as confirmed by multivariate regression analysis.ConclusionsBased on the inferior oncological outcomes and higher locoregional recurrence rate, this study highlighted the need for intensified cytotoxic chemotherapy specific to this recurrence pattern for patients with stage IIB/C colon cancer.

Revisiting the survival paradox between stage IIB/C and IIIA colon cancer.

Patients with stage IIB/C (T4a-bN0) colon cancer often exhibit worse survival rates compared to those with stage IIIA (T1-2N1, T1N2a) colon cancer. This study re-evaluates the survival paradox using the latest Surveillance, Epidemiology, and End Results (SEER) data (released on April 17, 2024) to inform potential revisions to the staging criteria. Utilizing SEER data with 8th edition TNM staging criteria, 4692 colon cancer patients diagnosed between 2018 and 2021 were analyzed with chi-square test. Cox regression and Kaplan-Meier survival analysis were employed to assess factors associated with cancer-specific survival (CSS) and overall survival (OS). The 3-year CSS rates for stage IIB and IIC were 73.1% and 70.3%, respectively, whereas stage IIIA had a substantially higher CSS rate of 91% (P < 0.001). Similarly, the OS rates were 64.9% and 63.0% for stage IIB and IIC, respectively, compared to 83.1% for stage IIIA (P < 0.001). Multivariate analyses revealed stage IIIA patients had significantly lower risks of cancer-specific mortality (hazard ratio (HR) = 0.374, 95% CI: 0.296-0.473, P < 0.001) and overall mortality (HR = 0.575, 95% CI: 0.483-0.685, P < 0.001) compared to stage IIB patients. The upcoming 9th edition of the AJCC staging system should address this paradox by integrating advanced diagnostic markers and emphasizing the aggressive biology of T4 tumor, providing more accurate prognostic information and guiding more effective treatment strategies for colon cancer patients.

Survival paradox between stage IIB/C and stage IIIA colon cancer: is it time to revise the American Joint Committee on Cancer TNM system?

A survival paradox between T4N0 (Stage IIB/IIC) and Stage IIIA colon cancer exists, even after adjusting for adequate lymph node (LN) retrieval and receipt of adjuvant chemotherapy (C). We conducted a large hospital-based study to re-evaluate this survival paradox based on the newest 8th edition staging system. The National Cancer Data Base was queried to evaluate 35,606 patients diagnosed with Stage IIB, IIC, and IIIA colon cancer between 2010 and 2017. The Kaplan-Meier method and log-rank test were used to compare unadjusted overall survival (OS). Multivariable Cox proportional hazards model was used to determine the association of stage with hazard ratios adjusted for relevant demographic and clinical variables including ≥ 12 LNs retrieved and receipt of adjuvant chemotherapy. P value < 0.05 was considered statistically significant. The 5-year OS for optimally treated stage IIIA colon cancer (receipt of C) was 84.3%, which was significantly higher than stage IIB/C (≥ 12 LNs retrieved + C) (72.8%; P < 0.0001). Stage was an independent predictor of OS. Among optimally treated Stage IIIA patients, T1N1 had the best survival (90.6%) while stage T4bN0 (stage IIC) had the worst (70.9%) (P < 0.0001). Compared to stage IIB, stage IIC had a 17% increased risk of overall death while stage IIIA had a 21% reduction in death (P < 0.0001). Stage IIB/C and Stage IIIA survival paradox persists even after accounting for receipt of adjuvant chemotherapy and adequate lymph node retrieval. Future iteration of the TNM system should take this paradox into consideration.

Chemotherapy exacerbates the survival paradox of colon cancer: a propensity score matching analysis.

Colon cancer is one of the most common tumor diseases in the world. Currently, clinicians usually evaluate the survival and prognosis of patients according to their tumor-node-metastasis (TNM) stage. However, current studies have found that there is a certain survival paradox in TNM staging. In the Surveillance, Epidemiology, and End Results (SEER) database, patients diagnosed with colon cancer by surgical pathology from 2004 to 2011 were selected for analysis of 5-year overall survival (OS). Propensity score matching (PSM) was performed to analyze the difference in survival between different stages and the effect of chemotherapy on prognosis. The OS of stage IIIA colon cancer sufferers was significantly superior to stage IIB/IIC and separate stage IIB or IIC colon cancer patients before and after PSM analysis (P<0.05 for all). Moreover, the difference in survival was more significant when stage IIB/IIC patients were compared with stage IIIA patients with chemotherapy. The survival paradox existed both in all stage IIB/IIC patients, or individual stage IIB or IIC patients compared with stage IIIA sufferers, and the survival paradox between stage IIIA and stage IIC was more obvious. Moreover, chemotherapy had a positive effect on the prognosis of patients with stage IIIA, IIC and IIB in this study. Chemotherapy exacerbates the survival paradox of colon cancer, even if it is not the cause of the survival paradox.

Survival Contradiction in Stage II, IIIA, And IIIB Colon Cancer: A Surveillance, Epidemiology, and End Result-Based Analysis.

There exists an inconsistency between stage and survival in the current American Joint Committee on Cancer (AJCC) staging system for colon cancer. In this study, we compared the clinicopathological characteristics and prognosis of colon cancer patients with stage II, IIIA, and IIIB disease based on the surveillance, epidemiology, and end results (SEER) database. Kaplan-Meier analysis was used to generate overall survival (OS) and cancer-specific survival (CSS) curves. The Cox regression was employed to identify risk factors. The competing risk model was completed by the cumulative incidence function and Gray's test. In the final population of 31,361 colon cancer patients, Kaplan-Meier curve analysis showed that stage IIIA had the highest OS and CSS, followed by stage IIA and IIIB, and IIB and IIC showed the worst OS and CSS. In the Cox model, the stage was proven to be an independent prognostic factor. In the competing risk model, stage IIIA colon cancer patients had the lowest 5-year cancer-specific death rate in stages II, IIIA, and IIIB. In conclusion, the prognosis of colon cancer patients in stage IIA was worse than that of patients in stage IIIA, while the survival rate of stage IIB and IIC was lower than that of stage IIIB.

What are the problems with the current staging of discontinuous tumour nodules (DTNs) in colorectal carcinoma? Is there a better way?

Discontinuous extramural tumour nodules (DTNs) are deposits of metastatic carcinoma in soft tissue not associated with lymph nodes. Although they are established as an adverse prognostic factor in colorectal carcinoma (CRC), under the AJCC eighth edition staging system their presence does not upstage patients who also have lymph node metastases. Counterintuitively, in some situations the presence of lymph node metastases may in effect downstage a patient with DTNs from pN1c to pN1a/b. Therefore, we sought to critically assess the significance of DTNs in a large unselected single institution cohort of patients undergoing surgical resection for CRC. Of 3822 CRC patients undergoing surgical resection from 2005 to 2021, DTNs were present in 686 (18.0%). In univariate (HR=2.687, 95CI 2.355-3.065; p<0.001) and multivariate analysis (HR=1.805, 95CI 1.529-2.132; p<0.001) in a model including age, gender, stage, grade, location, lymph node ratio and apical lymph node status, DTNs were associated with worse overall survival (OS). N1c patients (DTN present but no nodal metastasis) demonstrated worse OS compared to the current pN1a group (p<0.001) and were least different to the current pN2a group (p=0.571). Within the current N1a (p=0.013), N1b (p=0.004) and N2a (p=0.002) groups, patients who also had DTNs had worse OS. DTNs were associated with worse OS for all stage III CRCs combined (p<0.001), and for stage IIIB (p<0.001) and stage IIIC (p=0.007) individually. We conclude that DTNs are an independent adverse prognostic factor that should be considered in the staging system in a way that is additional to (rather than integrated with) the number of involved lymph nodes. We then assess a simple suggestion for how this could be achieved by increasing the overall stage by one group in the presence of DTNs (requiring the creation of a new stage IIID).

Number of negative lymph nodes with a positive impact on survival of stage III colon cancer; a retrospective observation study for right side and left side colon

BackgroundThe purpose was to examine the effect of negative lymph nodes (NLN) number on survival in stage III colon cancer. To reduce the interference of acute inflammation, we included patients with stage III colon cancer who had undergone elective surgery and excluded those who had tumor perforation, obstruction, ischemia, or massive tumor bleeding.MethodsThis retrospective cohort study included 2244 patients with stage III colon cancer between 1995 and 2016 at a single center. The effect of NLN on 5-year relapse-free survival (RFS), 5-year overall survival (OS), and comparison of multivariate factors was assessed according to tumor locations.ResultsThe two optimal cutoff values of NLN for proximal and distal colon, namely 27 and 12, were determined by plotting the time-dependent receiver operating characteristic curve. Overall, 499 of 891 and 1020 of 1353 patients with right-side and left-side colon cancer, respectively, had high NLN. In right-side colon cancer, patients with high NLN (≥ 27) had superior OS (74.9% vs. 62.7%, P < 0.001) and RFS (75.0% vs. 61.9%, P < 0.001) than did those with low NLN. Moreover, in left-side colon cancer, patients with high NLN (≥12) experienced significantly superior OS (80.8% vs. 68.6%, P < 0.001) and RFS (77.3% vs. 66.2%, P < 0.001) than did those with low NLN. Among the different subgroups of stage III colon cancer, the high NLN group showed significantly superior RFS and OS in stage IIIB (RFS: 77.0% vs. 68.0%, P = 0.001; OS: 78.6% vs. 67.9%, P < 0.001) and IIIC (RFS: 58.2% vs. 44.1%, P = 0.001; OS: 65.7% vs. 51.1%, P < 0.001) colon cancer. However, in stage IIIA colon cancer, high NLN only showed survival benefit in OS (91.5% vs. 89.8%, P = 0.041). Multivariate analyses confirmed that high NLN, high carcinoembryonic antigen (≥ 5 ng/mL) level, and stage IIIC status are three independent prognostic factors in both the proximal and distal colon.ConclusionsNLN is a crucial prognostic factor for stage III colon cancer in various tumor locations or in the subgroups of stage III disease. In advanced stage III colon cancer, the importance of NLN and its role in anti-cancer immune response could be highlighted.

MiRNA Profile and Bioinformatic Analysis for Diagnosis in Patients with Stage IIIA Colon Cancer.

Early diagnosis is a critical factor in deciding the outcome of colon cancer, as is the case with other types of cancers. Recent scientific developments have enabled the use of biomarkers for diagnosis and for designing treatment strategies for various cancer types. Further, identification of potential targets of these biomarkers will facilitate a better understanding of molecular processes. The aim of this study is to analyze microRNA expression profile, and through bioinformatic analyses determine the cellular processes of potential target genes and understand their molecular mechanism in stage IIIA colon cancer patients. The microRNA expression profiles of both normal and tumor tissues of seven patients were analyzed using the Affymetrix microarray system. The target genes were identified by performing a KEGG pathway analysis on eight miRNAs (hsa-miR-362-3p, hsa-miR-34c-5p, hsa-miR-34c-3p, hsa-miR-34a-3p, hsa-miR-19b-1-3p, hsa-miR-371a-5p, hsa-miR-941 ad hsa-miR-7-5p), which were selected through an array scan by using DIANA-miRPath v.3 bioinformatic analysis tool. Biological pathway and cellular component analyses were performed on 30 genes targeted by miRNAs using FunRich Gene Enrichment tool. These analyses indicated that the genes targeted by these eight miRNAs played a role in either cell communication (53%), signal transduction (60%) or apoptosis (20%) in stage IIIA colon cancer. Taken together, these data suggest that these miRNAs can be used as biomarkers in Stage IIIA colon cancer.

Re-Evaluation of the Survival Paradox Between Stage IIB/IIC and Stage IIIA Colon Cancer.

ObjectiveWe conducted this large population-based study to re-evaluate the survival paradox between stage IIB/C and stage IIIA colon cancer based on the newest staging criteria.MethodsColon cancer patients were recruited from the Surveillance, Epidemiology, and End Results (SEER) database using SEER*Stat software (version 8.3.4) with strict inclusion criteria. We used Chi-square test to compare categorical variables between patients diagnosed with stage IIB/IIC and stage IIIA colon cancer. Survival probabilities were then assessed using the Kaplan–Meier method. Cox proportional hazards models were used to analyze hazard ratios (HRs) and 95% confidence intervals (CIs) of clinicopathologic characteristics in stage IIB/IIC and stage IIIA colon cancer patients.ResultsIn the current study, a total of 9,227 eligible colon cancer patients were collected from the SEER database between 2010 and 2015. It was found that stage IIIA had 66.4% decreased risk of colon cancer-specific mortality compared with stage IIB (HR = 0.336, 95%CI = 0.286–0.394 for stage IIIA, P < 0.001, using stage IIB as the reference) after the adjustment for other known prognostic factors. And T1N2a colon cancer had significantly lower 5-year overall survival (OS) rate compared with T2N1 disease (74.7% vs. 57.1%, P = 0.018).ConclusionsOur study confirmed the existence of survival paradox between stage IIB/IIC and stage IIIA colon cancer based on the newest staging criteria. What is more, the subgroup analyses revealed that T1N2a had the least influence on the survival paradox. N2a colon cancer seemed to be associated with worse prognosis than T2 disease, which would give us a better understanding of tumor biology of colon cancer and be conducive to the refinement of individualized treatment regimens in stage III disease.

Controversial Issues Regarding Obligatory Adjuvant Chemotherapy for Stage IIIA Colon Cancer

PurposeTo investigate the survival outcomes of patients with stage IIIA colon cancer. In addition, risk factors that affect the oncologic outcome of stage IIIA colon cancer patients and the role of adjuvant chemotherapy were evaluated. Patients and MethodsData from 326 colon cancer patients with stage IIIA who underwent surgery between January 2000 and December 2016 were retrospectively reviewed. Patients diagnosed with hereditary cancer and those who received preoperative neoadjuvant therapy were excluded. ResultsThe 5-year recurrence-free survival (RFS) rate in stage IIIA colon cancer patients who underwent curative resection was 93.9%. Of the patients with recurrence, the survival rate of those who underwent surgical resection was better than that of patients who received palliative chemotherapy or no treatment (12/13, 92.3% vs. 2/4, 50.0%), respectively; P = .052). Multivariate analysis showed that high serum carcinoembryonic antigen (s-CEA) was an independent and statistically significant prognostic factor for RFS, and ulcerative gross-type disease tended to be a poor prognostic factor. There was no difference in RFS in patients with elevated s-CEA or ulcerative gross-type disease according to receipt of adjuvant chemotherapy. ConclusionPatients with stage IIIA colon cancer had a relatively favorable survival outcome. Even in patients with relapsed disease, long-term survival could be a result if surgical resection is accomplished. High s-CEA concentration is a significant poor prognostic factor for recurrence, and ulcerative gross-type disease tends to be a poor prognostic factor. Postoperative adjuvant chemotherapy may not provide a survival benefit for stage IIIA colon cancer, even in the presence of risk factors. Because of the rarity of this patient group and the low rate of recurrence, large-scale multicenter studies are needed to find and confirm the risk group that would receive a benefit from adjuvant chemotherapy.

Clinicopathological and biomolecular characteristics of stage IIB/IIC and stage IIIA colon cancer: Insight into the survival paradox.

A survival paradox of stage IIB/IIC and IIIA colon cancer has been consistently observed throughout revisions of the TNM system. This study aimed to understand this paradox with clinicopathological and molecular differences. Clinicopathological characteristics of patients with pathologically confirmed stage IIB/IIC or IIIA colon cancer were retrospectively reviewed from a database. Publicly available molecular data were retrieved, and intrinsic subtypes were identified and subjected to gene sets enrichment analysis (GSEA). Among the 159 patients included in the clinicopathological analysis, those at stage IIB/IIC had worse 3-year disease-free and overall survival than those at stage IIIA (59.3% vs 91.7%, P < 0.001 and 82.7% vs 98.5%, P < 0.001, respectively), even after adjusting for confounding factors. Data of 95 patients were retrieved from public databases, demonstrating a higher frequency of the microsatellite instable subtype in stage IIB/IIC. The consensus molecular subtype distribution pattern differed between the groups. The GSEA further suggested the protumor inflammatory reaction might be more prominent in stage IIB/IIC. The survival paradox in colon cancer was confirmed and appears to be a multifactorial phenomenon not attributed to a single clinicopathologic factor. However, the greater molecular heterogeneity in stage IIB/IIC could contribute to the poor prognosis.

Use of antidepressants after colon cancer diagnosis and risk of recurrence.

Prior research examining the association between use of antidepressants after colon cancer diagnosis and risk of recurrence is scant. We evaluated this association among colon cancer patients diagnosed at two integrated health care delivery systems in the United States. We conducted a cohort study of stage I to IIIA colon cancer patients diagnosed at greater than or equal to 18years of age at Kaiser Permanente Colorado and Kaiser Permanente Washington during 1995 to 2014. We used pharmacy records to identify dispensings for antidepressants and tumor registry records and patients' medical charts to identify cancer recurrences. Using Cox proportional hazards models, we estimated the adjusted hazard ratio (HR) of colon cancer recurrence comparing patients who used antidepressants after diagnosis to those who did not. We also evaluated the risk associated with use of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) separately. Among the 1923 eligible colon cancer patients, 807 (42%) used an antidepressant after diagnosis and 139 had a colon cancer recurrence during an average 5.6years of follow-up. Use of antidepressants after colon cancer diagnosis was not associated with risk of recurrence (HR: 1.14; 95% confidence interval [CI], 0.69-1.87). The HR for use of SSRIs was 1.22 (95% CI, 0.64-2.30), and for TCAs, it was 1.18 (95% CI, 0.68-2.07). Our findings suggest that use of antidepressants after colon cancer diagnosis was common and not associated with risk of recurrence. Future larger studies with greater power to examine risk associated with individual antidepressants would be valuable additions to the evidence base.

Right- and left-sided stage III colon cancers present different prognostic outcomes of oxaliplatin-based adjuvant chemotherapy after curative resection.

BackgroundGrowing evidence has suggested that right-sided colon cancer (RCC) and left-sided colon cancer (LCC) should be considered as different tumor entities. However, stage III colon cancer is currently treated as the same entity with uniform therapy. This study was aimed at investigating the prognostic influence of tumor location in patients with stage III colon cancer receiving adjuvant chemotherapy after curative resection.Patients and methodsWe retrospectively analyzed 274 eligible patients with stage III colon cancer undergoing curative tumor resection followed by adjuvant chemotherapy with oxaliplatin and capecitabine between December 2007 and December 2013. Disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan–Meier and log-rank tests, and prognostic factors were identified by Cox regression methods.ResultsPatients with RCC exhibited lower hemoglobin levels (23.6% vs. 9.8%; P = 0.002), larger tumor size (60.6% vs. 40.9%; P = 0.001), and a higher proportion of 12 or more resected lymph nodes (86.4% vs. 64.6%; P < 0.001) than patients with LCC. Grade 1 neurotoxicity was more common in patients with RCC than in those with LCC (53.6% vs. 40.9%; P = 0.037). RCC was significantly associated with a shorter 3-year OS than LCC, whereas a difference was noted only for stage IIIC and not stage IIIA or stage IIIB colon cancer. Multivariate analyses revealed that RCC was independently associated with a worse 3-year OS (hazard ratio: 2.213; 95% CI: 1.063–4.606; P = 0.002). In addition, an increase in 3-year OS and DFS after 6–8 cycles of adjuvant chemotherapy was only observed in patients with RCC and not in those with LCC.ConclusionThis study indicated that RCC has a worse prognostic outcome for stage III colon cancer, and a full course of adjuvant chemotherapy should be suggested for patients with RCC.

Positive surgical margins contribute to the survival paradox between patients with stage IIB/C (T4N0) and stage IIIA (T1-2N1, T1N2a) colon cancer

The underlying reasons for the survival paradox between stage IIB/C and stage IIIA colon cancer are elusive. We hypothesized that positive margins contribute to this paradox. We evaluated a cohort of 16,471 patients with stage IIIA and stage IIB/C colon cancer from 709,583 cases diagnosed between 2003-2012 in the National Cancer Data Base. All patients had chemotherapy, and all stage IIB/C patients had ≥12 lymph nodes retrieved. Patients with stage IIIA were subdivided further into those with <12 lymph nodes retrieved and those with ≥12 lymph nodes retrieved. Univariable and multivariable survival analyses were used. The 5-year overall survival rate was 70.8% for stage IIB/C, 81.6% for stage IIIA with <12 lymph nodes, and 85.6% for stage IIIA with ≥12 lymph nodes (P<.0001). The 5-year overall survival rate was 84.3% for stage IIIA with no residual tumor, 74.8% for stage IIIA with residual tumor, 73.3% for stage IIB/C with no residual tumor, and 60.5% for stage IIB/C with residual tumor (P<.0001). Independent predictors (P<.01) of poor overall survival include stage IIB/C, advanced age, African American ethnicity, community cancer program, uninsured and Medicaid, low education level, high comorbidity index, and positive surgical margins. Positive surgical margins may contribute to the survival paradox between stage IIB/C and stage IIIA colon cancer patients.

Survival paradox between stage IIB/C (T4N0) and stage IIIA (T1-2N1) colon cancer.

The survival paradox between stage IIB/C (T4N0) and stage IIIA (T1-2N1) colon cancer remains in the 7th edition of the American Joint Committee on Cancer staging system. This multicenter study aimed to compare the oncologic outcomes of T4N0 and T1-2N1 colon cancers and to investigate the presumptive prognostic factors that might influence the survival paradox. Patients who underwent curative surgery for pT4N0 (n=224) and pT1-2N1 (n=135) primary colon cancer between January 1999 and December 2010 at five tertiary referral cancer centers were included for analysis. The clinicopathologic, treatment-related factors, and oncologic outcomes in terms of the 5-year overall survival (5-OS) and 5-year disease-free survival (5-DFS) were compared. The T4N0 group had significantly worse 5-OS and 5-DFS rates than the T1-2N1 group (5-OS: 84.0 vs. 92.3%, p=0.012; 5-DFS: 73.6 vs. 88.0%, p=0.001). T4N0 cancers more frequently showed elevated preoperative carcinoembryonic antigen, lower grade of differentiation, larger tumor size, and higher proportions of perineural invasion, microsatellite instability, obstruction, and perforation than T1-2N1 cancers. Peritoneal seeding and liver metastasis were the predominant recurrence pattern in the T4N0 and T1-2N1 groups, respectively (p=0.042). The T4N0 group showed inferior survival to the T1-2N1 group in postoperative adjuvant chemotherapy (5-OS: 87.1 vs. 93.2%, p=0.045; 5-DFS: 76.1 vs. 89.0%, p=0.001). T4N0 colon cancer had significantly worse oncologic outcomes than T1-2N1 cancer regardless of adjuvant chemotherapy. The survival paradox may result from the biologic aggressiveness of T4N0 colon carcinomas.

Efficacy of Postoperative Adjuvant Chemotherapy According to Prognostic Factor in Patients with Stage III Colon Cancer

Background: We retrospectively identified prognostic factors in patients with Stage III colon cancer and considered the effectiveness of postoperative adjuvant chemotherapy based on these prognostic factors. Methods: Two hundred and thirty four patients with lymph node metastases who underwent curative surgery for colon cancer between 1999 and 2005 were enrolled in the present study. Firstly, clinicopathological factors and survival data, were analyzed to determine prognostic factors related to cancer-specific survival. Secondly, we examined the effectiveness of postoperative adjuvant chemotherapy based upon these prognostic factors. Results: The multivariate analysis revealed that differentiation (P = 0.03, Hazard ratio = 2.50), lymphatic invasion (P = 0.02, Hazard ratio = 3.23) and the TNM classification, 7th edition (P = 0.04, Hazard ratio = 1.94) were found to be significant independent prognostic factors. Among the patients classified as TNM IIIA, the recurrence-free survival rates were extremely good. Among the patients classified as IIIB and IIIC, there was no significant difference between the patients with and without postoperative adjuvant chemotherapy. Conclusion: The present study suggests that the patients with Stage IIIA colon cancer may not require postoperative adjuvant chemotherapy. The addition of oxaliplatin to 5-FU should be considered for the patients with Stage IIIB and IIIC colon cancer, for whom the prognoses are far from satisfactory.

Stage IIIa結腸・直腸S状部癌根治切除症例における再発危険因子の検討

目的：Stage IIIa結腸・直腸S状部癌の根治切除例における再発危険因子を明らかにする．方法：当科で1990年～2007年の間にR0切除を行ったStage IIIa結腸・直腸S状部癌236例について，非再発群と再発群とに分けて検討した．成績：再発率は22.0％（52/236例）．単変量解析では術前CEA値，腫瘍最大径，壁深達度において無再発生存期間に有意差を認めた．多変量解析の結果では静脈侵襲あり，リンパ管侵襲あり，SE以深が独立した再発危険因子として抽出された（HR1.830，2.316，2.156，95％CI 1.009-3.320，1.206-4.449，1.204-3.863，p＝0.0467，0.0117，0.0098）．結論：Stage IIIa結腸・直腸S状部癌において脈管侵襲あり，SE以深の症例は再発リスクが高いと考えられ，積極的な術後補助化学療法を考慮すべきと考えられる．

522PD - Development and Validation of a Robust Molecular Diagnostic Test (COLOPRINT) for Predicting Outcome in Stage II Colon Cancer Patients

ABSTRACT Background Only between 25 to 35% of stage II and IIIA colon cancer patients will experience a relapse of their disease and may benefit from adjuvant chemotherapy. ColoPrint is a gene expression classifier that can predict disease relapse in patients with early-stage colorectal cancer and helps to identify patients with higher risk of relapse. Methods ColoPrint was developed using whole genome expression data and was validated in public datasets and an independent patient cohort of 206 patients (Salazar et al., JCO 2011). The signature was translated to a customized 8-pack microarray. Positive and negative hybridization control genes monitor the quality of hybridization and a colon specific normalization gene set (n = 461) guarantee reliability of results. Reproducibility and precision studies with 20 times 6 samples were performed by multiple operators on multiple days. Additional independent patient cohorts were validated on the customized arrays. Uni- and multi-variate analyses were performed on the pooled stage II patient set (n = 320), the subset of T3/ MSS patients (n = 227) and stage IIIA (n = 16). Results The prognostic classifier was evaluated in reproducibility and stability assays and stringent quality controls were established following the successful lead of the FDA-cleared MammaPrint assay. Results of all tests met the pre-set criteria. In the analysis of all stage II and IIIA patients, ColoPrint classified two-third of patients as being at low risk. The 3-year Relapse-Free-Survial (RFS) RFS was 92% and 77% for low and high risk patients respectively with a HR of 2.9 (p = 0.001). Clinical and pathological risk parameters from the NCCN guidelines can be combined with ColoPrint for even more personalized risk assessment. ColoPrint is also able to distinguish risk groups in the subgroup of patients with T3 and MSS phenotype (HR= 2.7, p = 0.01) and IIIA (HR= 3.6, p = 0.08). Conclusions ColoPrint was technically and clinically validated and is now available for diagnostic use. ColoPrint significantly improves prognostic accuracy, thereby facilitating the identification of patients at higher risk who might be considered for additional treatment. Disclosure I. Simon: Employee of Agendia (maker of ColoPrint). J. van der Akker: Employee of Agendia (maker of ColoPrint). Y. Li: Employee of Agendia (maker of ColoPrint). B. Chan: Employee of Agendia (maker of ColoPrint). A. Glas: Employee of Agendia (maker of ColoPrint). All other authors have declared no conflicts of interest.

O-0025 Personalized Treatment Planning of Stage II and IIIA Colon Cancer Patients using Genomic Classifiers (ColoPrint/ MSI-Print)

ABSTRACT Introduction Adjuvant therapy for stage II patients is recommended for patients with high risk features, especially with T4 tumors, and recommended for all stage III patients. Adjuvant therapy is not indicated for patients with MSI-H status who are considered of being at low risk of disease relapse. However, this leaves the majority of stage II patients with an undetermined risk. ColoPrint is an 18-gene expression classifier that identifies patients at higher risk of disease relapse. Together with a genomic classifier to determine MSI-status, ColoPrint can help making treatment decisions for early stage colon cancer patients. Methods ColoPrint was developed using whole genome expression data and was validated in public datasets (n = 322) and independent patient cohorts from 5 European hospitals (n = 341). Tissue specimen, clinical parameters, MSI-status and follow-up data (median follow-up 70 months) for patients were available and the ColoPrint index was determined using validated diagnostic arrays. The 64-gene MSI-signature (MSI-Print) was developed using full genome expression data of 276 primary stage II and III colorectal tumors with known MSI-status (n = 29 MSI-H, n = 247 MSS). Uni-and multivariate analysis was performed on the pooled stage II and stage IIIA patient set and in the subsets of patients who were stage IIIA or stage II T3/ MSS. Results In the analysis of all stage II and IIIA patients, ColoPrint classified two-third of stage II patients as being at lower risk. The 3-year Relapse-Free-Survival (RFS) was 91% for Low Risk and 74% for patients at higher risk with a HR of 2.9 (p = 0.001). Clinicopathological parameters from the 2012 NCCN guidelines (T4, perforation, Conclusion The diagnostic MSI signature identifies patients with MSI-H status with high accuracy. Combined with ColoPrint, the prognostic accuracy in stage II and stage IIIA patients can be significantly improved, thereby facilitating the identification of patients at higher risk who might be considered for additional treatment.

Oncologic Outcomes of Stage IIIA Colon Cancer for Different Chemotherapeutic Regimens

PurposeAdjuvant chemotherapy is currently recommended for Stage IIIA colon cancers. This study aimed to elucidate the oncologic outcomes of Stage IIIA colon cancer according to the chemotherapeutic regimen based on a retrospective review.MethodsFrom 1995 to 2008, Stage IIIA colon cancer patients were identified from a prospectively maintained database at a single institution. Exclusion criteria were as follows: rectal cancer, another malignancy other than colon cancer, no adjuvant chemotherapy and unknown chemotherapeutic regimen. One hundred thirty-one patients were enrolled in the study, and the clinicopathologic and the oncologic characteristics were analyzed. The number of males was 72, and the number of females was 59; the mean age was 59.5 years (range, 25 to 76 years), and the median follow-up period was 33 months (range, 2 to 127 months).ResultsOf the 131 patients, fluorouracil/leucovorin (FL)/capecitabine chemotherapy was performed in 109 patients, and FOLFOX chemotherapy was performed in 22 patients. When the patients who received FL/capecitabine chemotherapy and the patients who received FOLFOX chemotherapy were compared, there was no significant difference in the clinicopathologic factors between the two groups. The 5-year overall survival and the 5-year disease-free survival were 97.2% and 94.5% in the FL/capecitabine patient group and 95.5% and 90.9% in the FOLFOX patient group, respectively, and no statistically significant differences were noted between the two groups.ConclusionStage IIIA colon cancer showed good oncologic outcomes, and the chemotherapeutic regimen did not seem to affect the oncologic outcome.