Causes of death in patients operated for colorectal cancer.

BACKGROUND: Colorectal cancer remains the third leading cause of cancer-related mortality in the United States. This study evaluates the causes of death in patients operated on for colorectal cancer and their determinants. METHODS: An Instructional Review Board-approved database containing patients who underwent surgical resection for colorectal cancer from 2004 to 2018 (last followed up in December 2020) in a tertiary care institution. Data on the underlying cause of death was extracted from the Registry of Vital Records and Statistics in Massachusetts. RESULTS: A total of 576 deaths were recorded in the database, of which 290 (50.35%) patients died of colorectal cancer. Deaths from colorectal cancer gradually decreased over time, whereas deaths from other cancers increased, and deaths from cardiovascular diseases remained stable. Patients who died from colorectal cancer were younger, died earlier in the disease course, had fewer comorbidities, higher rates of stage IV disease, rectal cancer, neoadjuvant therapy, extramural vascular invasion, perineural invasion, R0 resection, and preserved mismatch repair protein status. On multivariate analysis, age (adjusted odds ratio for 10-year increase = 0.79, 95% confidence interval 0.65-0.95), American Society of Anesthesiologists score (adjusted odds ratio = 0.64, confidence interval 0.42-0.98), stage IV disease (adjusted odds ratio = 3.02, confidence interval 1.59-5.9), neoadjuvant therapy (adjusted odds ratio = 7.91, confidence interval 2.64-28.13), extramural vascular invasion (adjusted odds ratio = 2.3, confidence interval 1.36-3.91) & time from diagnosis to death (adjusted odds ratio = 0.76, confidence interval 0.68-0.83) predicted death due to colorectal cancer versus other causes, whereas tumor location, perineural invasion, R0 resection, and mismatch repair protein status did not. CONCLUSION: There is a declining trend of deaths from colorectal cancer, presumably reflecting advances in colorectal cancer management strategies and better screening over time. However, younger patients disproportionately contribute to death due to colorectal cancer and need aggressive screening and management strategies.

Metformin Does not Affect Outcomes in Patients With Locally Advanced Rectal Cancer Treated With Neoadjuvant Therapy and Resection.

INTRODUCTION: There is emerging evidence that metformin may have a protective effect in patients with cancer. However, its current evidence in locally advanced rectal cancer (LARC) is inconclusive. We aim to assess the effect of metformin on long-term outcomes in patients with LARC who received neoadjuvant therapy and surgical resection. METHODS: A retrospective review of 324 patients with nonmetastatic LARC who received neoadjuvant therapy and major surgical resection from 2004 to 2018. There were 27 patients who received metformin before surgery and 297 patients who did not receive metformin. RESULTS: Metformin users were associated with a significantly higher age, BMI, ASA score, and 30-day readmissions (P < .05). There was no difference in overall survival (OS, P = .18) or disease-free survival (DFS, P = .33) between the two groups. On Cox regression, metformin intake did not predict OS (HR 0.85, 95% CI 0.4-1.77) when controlled for age (HR 1.04, 1.02-1.06), sex (HR 1.13, 0.69-1.85), BMI (HR 0.97, 0.92-1.02), ASA score (HR: 1.7, 1.06-2.73), TNT (HR 0.31, 0.1-0.92), pathological Stage III disease (HR 2.55, 1.51-4.32), extramural vascular invasion (EMVI) (HR 3.06, 1.7-5.5), and adjuvant therapy (HR 0.1, 0.04-0.27 for <25 months OS and HR 0.3, 0.15-0.59 for ≥25 months). Disease-free survival showed a similar trend with no significant effect of metformin (HR 0.77, 0.39-1.52) when controlled for age, sex, BMI, ASA, TNT, Stage III disease, EMVI, and adjuvant therapy. CONCLUSION: Metformin does not affect long-term survival in LARC treated with neoadjuvant therapy followed by surgical resection. Studies with larger sample sizes are needed to validate the findings further.

Trends and Determinants of Location of Death Due to Colorectal Cancer in the United States : A Nationwide Study.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States (US); however, there are limited data on location of death in patients who die from CRC. We examined the trends in location of death and determinants in patients dying from CRC in the US. METHODS: We utilized the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database to extract nationwide data on underlying cause of death as CRC. A multinomial logistic regression was performed to assess associations between clinico-sociodemographic characteristics and location of death. RESULTS: There were 850,750 deaths due to CRC from 2003 to 2019. There was a gradual decrease in deaths in hospital, nursing home, or outpatient facility/emergency department over time and an increase in deaths at home and in hospice. Relative to White decedents, Black, Asian, and American Indian/Alaska Native decedents were less likely to die at home and in hospice compared with hospitals. Individuals with lower educational status also had a lower risk of dying at home or in hospice compared with in hospitals. CONCLUSIONS: The gradual shift in location of death of patients who die of CRC from institutionalized settings to home and hospice is a promising trend and reflects the prioritization of patient goals for end-of-life care by healthcare providers. However, there are existing sociodemographic disparities in access to deaths at home and in hospice, which emphasizes the need for policy interventions to reduce health inequity in end-of-life care for CRC.

Incidence of Secondary Cancers After Neoadjuvant Therapy for Locally Advanced Rectal Cancer.

INTRODUCTION: Whether neoadjuvant chemoradiation for locally advanced rectal cancer (LARC) induces secondary cancers is controversial. This retrospective cohort study describes the incidence of secondary cancers in LARC patients. METHODS: We compared 364 LARC patients who received conventional (50.4 Gy) or short course neoadjuvant radiation (25 Gy x 5 fractions) followed by resection to 142 patients with surgically resected rectal cancer who did not receive radiation at a single institution from 2004 to 2018. Secondary cancer was defined as any nonmetastatic noncolorectal malignancy diagnosed via biopsy or definitive imaging criteria at least 6 mo after completion of neoadjuvant therapy or after resection in the comparison group. RESULTS: Among the neoadjuvant radiation group (364 patients, 40% female, age 61 ± 13 y), 32 patients developed 34 (9.3%) secondary cancers. Three cases involved a pelvic organ. Among the comparison group (142 patients, 39% female, age 64 ± 15 y), 15 patients (10.6%) developed a secondary cancer. Five cases involved pelvic organs. Secondary cancer incidence did not differ between groups. Latency period to secondary cancer diagnosis was 6.7 ± 4.3 y. Patients who received radiation underwent longer median follow-up (6.8 versus 4.5 y, P < 0.01) and were significantly less likely to develop a pelvic organ cancer (odds ratio 0.18; 95% confidence interval, 0.04-0.83; P = 0.02). No genetic mutations or cancer syndromes were identified among patients with secondary cancers. CONCLUSIONS: Neoadjuvant chemoradiation is not associated with increased secondary cancer risk in LARC patients and may have a local protective effect on pelvic organs, especially prostate. Ongoing follow-up is critical to continue risk assessment.

Colitis-Associated Colorectal Cancer Survival is Comparable to Sporadic Cases after Surgery: a Matched-Pair Analysis.

BACKGROUND: Inflammatory bowel disease (IBD) confers an increased lifetime risk of colorectal cancer (CRC). The pathogenesis of colitis-associated CRC is considered distinct from sporadic CRC, but existing is mixed on long-term oncologic outcomes. This study aims to compare clinicopathological characteristics and survival between colitis-associated and sporadic CRC. METHODS: Data was retrospectively extracted and analyzed from a single institutional database of patients with surgically resected CRC between 2004 and 2015. Patients with IBD were identified as having colitis-associated CRC. The remainder were classified as sporadic CRC. Propensity score matching was performed. Univariate and survival analyses were carried out to estimate the differences between the two groups. RESULTS: Of 2275 patients included in this analysis, 65 carried a diagnosis of IBD (2.9%, 33 Crohn's disease, 29 ulcerative colitis, 3 indeterminate colitis). Average age at CRC diagnosis was 62 years for colitis-associated CRC and 65 for sporadic CRC. The final propensity score matched cohort consisted of 65 colitis-associated and 130 sporadic CRC cases. Patients with colitis-associated CRC were more likely to undergo total proctocolectomy (p < 0.01) and had higher incidence of locoregional recurrence (p = 0.026) compared to sporadic CRC patients. There were no significant differences in time to recurrence, tumor grade, extramural vascular invasion, perineural invasion, or rate of R0 resections. Overall survival and disease-free survival did not differ between groups. On multiple Cox regression, IBD diagnosis was not a significant predictor of survival. CONCLUSIONS: Patients with colitis-associated CRC who undergo surgical resection have comparable overall and disease-free survival to patients with sporadic CRC.

Patient Factors Affecting Inpatient Mortality Following Colorectal Cancer Resection.

BACKGROUND: Our objective is to identify factors for inpatient death in patients undergoing resection for colorectal cancer (CRC). STUDY DESIGN: Unmatched 1:3 case-control study of surgically resected CRC at a tertiary care institution between 2004 and 2018. Variables for multivariate analysis were selected using tetrachoric correlation followed by a least absolute shrinkage and selection operator (LASSO) penalized regression model. RESULTS: A total of 140 patients were included (N = 35 patients who died inpatient, N = 105 patients who did not die). Patients who died were older, had higher Charlson Comorbidity Index (CCI), higher rates of preoperative anemia, hypoalbuminemia, emergency surgeries, blood transfusion, postoperative vasopressor requirement, anastomotic leak, and postoperative ICU admission than patients who underwent surgical resection without inpatient mortality. Anemia (aOR = 8.62, 1.44-91.58), emergency admission (aOR = 5.71, 1.46-24.36), and ICU admission (aOR 45.51, 8.31-448.4) significantly predicted inpatient mortality when controlled for CCI and hypoalbuminemia. CONCLUSIONS: Surprisingly, it appears that pre-existing anemia and perioperative factors are more important in predicting inpatient mortality of patients undergoing CRC surgery than baseline comorbidity or nutritional status.

Association of age with outcomes in locally advanced rectal cancer treated with neoadjuvant therapy followed by surgery.

INTRODUCTION: We aimed to assess the association of age with outcomes in patients with Locally Advanced Rectal Cancer (LARC) who received neoadjuvant therapy followed by major surgery. METHODS: Retrospective review of 328 patients with LARC, N = 99 < 70 years (younger) versus N = 229 ≥ 70 years (elderly) from 2004 to 2018. RESULTS: Elderly patients had a higher American Society of Anesthesiologists (ASA) score, Charlson Comorbidity Index (CCI), length of stay and 30-day readmissions (p < 0.05). They also had worse overall survival (OS) & disease-free survival (DFS) (p < 0.001), but similar disease-specific survival (DSS) compared to younger group. Age was not associated with hazard of death (HR 1.01, 0.98-1.03). Rather, CCI (HR 1.29, 1.01-1.5), extramural vascular invasion (HR 4.98, 2.84-8.74), and adjuvant therapy (0.37, 0.21-0.64) were significantly associated with the hazard of death; when controlled for stage, tumor distance from anal verge, and neoadjuvant completion. CONCLUSION: Comorbidities and lower rates of adjuvant therapy, and not chronologic age, are associated with poor OS of elderly patients with LARC treated with neoadjuvant therapy and major surgery.

Immunological and Clinico-Molecular Features of Tumor Border Configuration in Colorectal Cancer.

INTRODUCTION: Infiltrating tumor border configuration (ITBC) portends a poor prognosis compared with pushing tumor border configuration (PTBC) in colorectal cancer. The tumor and its surrounding immune microenvironment of tumor border configuration is not well-characterized. We aim to elucidate the differences in expression of molecular markers between the 2 groups using tissue microarray (TMA). STUDY DESIGN: Immunohistochemistry was performed on TMAs of surgical pathology specimens obtained from colorectal cancer patients consecutively operated at our institution from 2004 to 2015. TMAs were stained for immune cells (CD8, FOXP3, LAG3, PU1, CD163, and PDL1); HLA II, beta 2 microglobulin, and HC10 on tumor cells; BRAFV600E mutation; and DNA mismatch repair proteins (MMR) status. Patients who received neoadjuvant therapy were excluded. RESULTS: There were 646 tumors with ITBC and 310 tumors with PTBC. There was a significantly lower expression (p < 0.05) of immune components, namely CD8, FOXP3, LAG3, PU1, PDL1 immune cells, and Beta-2 Microglobulin on tumor cells in the tumors with ITBC compared with PTBC, except CD163 immune cells, and HC10 and HLAII on tumor cells. Tumors with ITBC were less likely to be associated with BRAFV600E mutations and deficient MMR proteins (p < 0.001). On analyzing MMR-proficient tumors separately, we could not find any difference in the expression of any molecular marker (including BRAF), except a lower expression of PDL1 immune cells in tumors with ITBC (p < 0.001). CONCLUSIONS: Colorectal tumors with ITBC are associated with a generalized low immune microenvironment and low rates of BRAFV600E mutation compared with tumors with PTBC. However, the molecular expression of tumor border configuration seems confounded by the MMR molecular signature. MMR-proficient colorectal tumors with ITBC are associated with a lower expression of only PDL1 immune cells among all immune markers examined.

The time Interval Between the End of Radiotherapy and Surgery Does Not Affect Outcomes in Rectal Cancer.

INTRODUCTION: The ideal time interval between the completion of chemoradiotherapy and subsequent surgical resection of advanced stage rectal tumors is highly debated. Our aim is to study the effect of the time interval between the completion of chemoradiotherapy and surgical resection on postoperative and oncologic outcomes in rectal cancer. METHODS: Patients who underwent neoadjuvant chemoradiotherapy for resected locally advanced rectal tumors between 2004 and 2015 were included in this analysis. The time interval was calculated from the date of radiation completion to date of surgery. Patients were split into 2 groups based on the time interval (<8 weeks and >8 weeks). Postoperative outcomes (anastomotic leak, pathologic complete response (pCR), and readmission) and survival were assessed with multivariable logistic regression and Cox regression models while adjusting for relevant confounders. RESULTS: 200 patients (62% male) underwent resection with a median time interval of 8 weeks from completion of radiotherapy. On multivariable logistic regression, there was no significant increase in odds between time interval to surgery and anastomotic leak (aOR = .8 [.27-2.7], P = .8), pCR (aOR = 1.2[.58-2.6] P = .6), or readmission (aOR = 1.02, 95% CI:0.49-2.24, P = .9). Time interval to surgery was not an independent prognostic factor for overall (HR = 1.04 CI = .4-2.65, P = .9) and disease-free survival (HR = 1.2 CI = .5-2.9, P = .6). CONCLUSION: The time interval between neoadjuvant radiotherapy completion and surgical resection does not affect anastomotic leak rate, achievement of pCR, or overall and disease-free survival in patients with rectal cancer. Extended periods of time to surgical resection are relatively safe.

Molecular Basis of Extramural Vascular Invasion (EMVI) in Colorectal Carcinoma.

BACKGROUND: Extramural vascular invasion (EMVI) is a known poor prognostic factor in colorectal carcinoma; however, its molecular basis has not been defined. This study aimed to assess the expression of molecular markers in EMVI positive colorectal carcinoma to understand their tumor microenvironment. METHODS: Immunohistochemistry was performed on tissue microarrays of surgically resected colorectal cancer specimens for immunological markers, and BRAFV600E mutation (and on the tissue blocks for mismatch repair proteins). Automated quantification was used for CD8, LAG3, FOXP3, PU1, and CD163, and manual quantification was used for PDL1, HLA I markers (beta-2 microglobulin, HC10), and HLA II. The Wilcoxon rank-sum test was used to compare EMVI positive and negative tumors. A logistic regression model was fitted to assess the predictive effect of biomarkers on EMVI. RESULTS: There were 340 EMVI positive and 678 EMVI negative chemo naïve tumors. PDL1 was barely expressed on tumor cells (median 0) in the entire cohort. We found a significantly lower expression of CD8, LAG3, FOXP3, PU1 cells, PDL1 positive macrophages, and beta-2 microglobulin on tumor cells in the EMVI positive subset (p ≤ 0.001). There was no association of BRAFV600E or deficient mismatch repair proteins (dMMR) with EMVI. PU1 (OR 0.8, 0.7-0.9) and low PDL1 (OR 1.6, 1.1-2.3) independently predicted EMVI on multivariate logistic regression among all biomarkers examined. CONCLUSION: There is a generalized blunting of immune response in EMVI positive colorectal carcinoma, which may contribute to a worse prognosis. Tumor-associated macrophages seem to play the most significant role in determining EMVI.

Tumour genotypes account for survival differences in right- and left-sided colon cancers.

AIM: We sought to identify genetic differences between right- and left-sided colon cancers and using these differences explain lower survival in right-sided cancers. METHOD: A retrospective review of patients diagnosed with colon cancer was performed using The Cancer Genome Atlas, a cancer genetics registry with patient and tumour data from 20 North American institutions. The primary outcome was 5-year overall survival. Predictors for survival were identified using directed acyclic graphs and Cox proportional hazards models. RESULTS: A total of 206 right- and 214 left-sided colon cancer patients with 84 recorded deaths were identified. The frequency of mutated alleles differed significantly in 12 of 25 genes between right- and left-sided tumours. Right-sided tumours had worse survival with a hazard ratio of 1.71 (95% confidence interval 1.10-2.64, P = 0.017). The total effect of the genetic loci on survival showed five genes had a sizeable effect on survival: DNAH5, MUC16, NEB, SMAD4, and USH2A. Lasso-penalized Cox regression selected 13 variables for the highest-performing model, which included cancer stage, positive resection margin, and mutated alleles at nine genes: MUC16, USH2A, SMAD4, SYNE1, FLG, NEB, TTN, OBSCN, and DNAH5. Post-selection inference demonstrated that mutations in MUC16 (P = 0.01) and DNAH5 (P = 0.02) were particularly predictive of 5-year overall survival. CONCLUSIONS: Our study showed that genetic mutations may explain survival differences between tumour sites. Further studies on larger patient populations may identify other genes, which could form the foundation for more precise prognostication and treatment decisions beyond current rudimentary TNM staging.

Zip Code-Related Income Disparities in Patients With Colorectal Cancer.

INTRODUCTION: Screening and early detection reduce morbidity and mortality in colorectal cancer. Our aim is to study the effect of income disparities on the clinical characteristics of patients with colorectal cancer in Massachusetts. METHODS: Patients were extracted from a database containing all surgically treated colorectal cancers between 2004 and 2015 at a tertiary hospital in Massachusetts. We split patients into 2 groups: "above-median income" and "below-median income" according to the median income of Massachusetts ($74,167). RESULTS: The analysis included 817 patients. The above-median income group consisted of 528 patients (65%) and the below-median income group consisted of 289 patients (35%). The mean age of presentation was 64 ± 15 years for the above-median income group and 67 ± 15 years for the below-median income group (P = .04). Patients with below-median income were screened less often (P < .001) and presented more frequently with metastatic disease (P = .02). Patients with above-median income survived an estimated 15 months longer than those with below-median income (P < .001). The survival distribution was statistically significantly different between the groups for stage III disease (P = .004), but not stages I, II, or IV (P = 1, 1, and .2, respectively). For stage III disease, a lower proportion of below-median income patients received chemotherapy (61% vs. 79%, P = .002) and a higher proportion underwent nonelective surgery (5% vs. 2%, P = .007). CONCLUSIONS: In Massachusetts, patients with colorectal cancer residing in lower income areas are screened less, received adjuvant chemotherapy less, and have worse outcomes, especially when analyzing those who present with stage III disease.

Response prediction of neoadjuvant chemoradiation therapy in locally advanced rectal cancer using CT-based fractal dimension analysis.

OBJECTIVES: There are individual variations in neo-adjuvant chemoradiation therapy (nCRT) in patients with locally advanced rectal cancer (LARC). No reliable modality currently exists that can predict the efficacy of nCRT. The purpose of this study is to assess if CT-based fractal dimension and filtration-histogram texture analysis can predict therapeutic response to nCRT in patients with LARC. METHODS: In this retrospective study, 215 patients (average age: 57 years (18-87 years)) who received nCRT for LARC between June 2005 and December 2016 and underwent a staging diagnostic portal venous phase CT were identified. The patients were randomly divided into two datasets: a training set (n = 170), and a validation set (n = 45). Tumor heterogeneity was assessed on the CT images using fractal dimension (FD) and filtration-histogram texture analysis. In the training set, the patients with pCR and non-pCR were compared in univariate analysis. Logistic regression analysis was applied to identify the predictive value of efficacy of nCRT and receiver operating characteristic analysis determined optimal cutoff value. Subsequently, the most significant parameter was assessed in the validation set. RESULTS: Out of the 215 patients evaluated, pCR was reached in 20.9% (n = 45/215) patients. In the training set, 7 out of 37 texture parameters showed significant difference comparing between the pCR and non-pCR groups and logistic multivariable regression analysis incorporating clinical and 7 texture parameters showed that only FD was associated with pCR (p = 0.001). The area under the curve of FD was 0.76. In the validation set, we applied FD for predicting pCR and sensitivity, specificity, and accuracy were 60%, 89%, and 82%, respectively. CONCLUSION: FD on pretreatment CT is a promising parameter for predicting pCR to nCRT in patients with LARC and could be used to help make treatment decisions. KEY POINTS: • Fractal dimension analysis on pretreatment CT was associated with response to neo-adjuvant chemoradiation in patients with locally advanced rectal cancer. • Fractal dimension is a promising biomarker for predicting pCR to nCRT and may potentially select patients for individualized therapy.

Is Microsatellite Status Associated With Prognosis in Stage II Colon Cancer With High-Risk Features?

BACKGROUND: The influence of microsatellite instability on prognosis in high-risk stage II colon cancer is unknown. OBJECTIVE: This study aimed to investigate the relationship between microsatellite instability and overall survival in high-risk stage II colon cancer. DESIGN: This is a retrospective review of the National Cancer Database from 2010 to 2016. SETTINGS: This study included national cancer epidemiology data from the American College of Surgeons Commission on Cancer. PATIENTS: Included were 16,788 patients with stage II colon adenocarcinoma and known microsatellite status (1709 microsatellite unstable). MAIN OUTCOME MEASURES: The primary outcome measured was overall survival. RESULTS: Microsatellite unstable cancers with high-risk features had significantly better overall survival than microsatellite stable cancers with high-risk features (5-year survival 80% vs 72%, p = 0.01), and had survival equivalent to microsatellite stable cancers with low-risk features (5-year survival, 80%). When stratified by specific high-risk features, patients with lymphovascular invasion, perineural invasion, or high-grade histology had overall survival similar to patients without these features, only in microsatellite unstable cancers. However, patients with high-risk features of T4 stage, positive margins, and <12 lymph nodes saw no survival benefit based on microsatellite status. This was confirmed on multivariable Cox regression modeling. A subgroup analysis of patients who did not receive chemotherapy similarly demonstrated that microsatellite unstable cancers with lymphovascular invasion, perineural invasion, or high-grade histology had overall survival similar to microsatellite unstable cancers without those features. LIMITATIONS: The study is limited by the lack of specific clinical data and potential treatment bias. CONCLUSIONS: In microsatellite unstable cancers, lymphovascular invasion, perineural invasion, and high-grade histology are not associated with worse overall survival, even when deferring adjuvant chemotherapy. These data support National Comprehensive Cancer Network recommendations to forego chemotherapy in stage II cancers with microsatellite instability and these features. In contrast, some high-risk features were associated with worse survival despite microsatellite unstable biology, and therapies to improve survival need to be explored. See Video Abstract at http://links.lww.com/DCR/B500. ¿EL ESTADO MICROSATÉLITE ESTÁ ASOCIADO CON EL PRONÓSTICO EN EL CÁNCER DE COLON EN ESTADIO II CON CARACTERÍSTICAS DE ALTO RIESGO: Se desconoce la influencia de la inestabilidad microsatélite en el pronóstico del cáncer de colon en estadio II de alto riesgo.Investigar la relación entre la inestabilidad microsatélite y la supervivencia general en el cáncer de colon en estadio II de alto riesgo.Revisión retrospectiva de la base de datos nacional del cáncer de 2010 a 2016.Este estudio incluyó datos nacionales de epidemiología del cáncer de la Comisión de Cáncer del Colegio Americano de Cirujanos.16,788 pacientes con adenocarcinoma de colon en estadio II y estado microsatélite conocido (1,709 microsatélite inestables).Supervivencia global.Los cánceres microsatélite inestables con características de alto riesgo tuvieron una supervivencia general significativamente mejor que los cánceres microsatélite estables con características de alto riesgo (supervivencia a 5 años 80% vs 72%, p = 0.01), y tuvieron una supervivencia equivalente a los cánceres microsatélite estables con características de bajo riesgo (supervivencia a 5 años 80%). Al estratificar por características específicas de alto riesgo, los pacientes con invasión linfovascular, invasión perineural o histología de alto grado tuvieron una supervivencia general similar a la de los pacientes sin estas características, solo en cánceres microsatélite inestables. Sin embargo, los pacientes con características de alto riesgo en estadio T4, márgenes positivos y <12 ganglios linfáticos no tuvieron ningún beneficio de supervivencia basado en el estado de microsatélites. Esto se confirmó en un modelo de regresión de Cox multivariable. Un análisis de subgrupos de pacientes que no recibieron quimioterapia demostró de manera similar que los cánceres microsatélite inestables con invasión linfovascular, invasión perineural o histología de alto grado tenían una supervivencia general similar a los cánceres microsatélite inestables sin esas características.El estudio está limitado por la falta de datos clínicos específicos y el posible sesgo de tratamiento.En los cánceres microsatélite inestables, la invasión linfovascular, la invasión perineural y la histología de alto grado no se asocian con una peor sobrevida general, incluso cuando se aplaza la quimioterapia adyuvante. Estos datos respaldan las recomendaciones de la National Comprehensive Cancer Network de omitir la quimioterapia en los cánceres en estadio II con inestabilidad microsatélite y estas características. Por el contrario, algunas características de alto riesgo se asociaron con una peor supervivencia a pesar de la biología microsatélite inestable, y es necesario considerar las terapias para mejorar la supervivencia.Consulte Video Resumen en http://links.lww.com/DCR/B500. (Traducción-Dr. Jorge Silva Velazco).