Survival In Rectal Cancer Research Articles

Radiation Therapy Improves Survival in Small Cell Rectal Cancer: Analysis of Surveillance, Epidemiology, and End Results (SEER) Data

Purpose/Objective(s): Small cell rectal cancer is a rare entity with scant literature to guide treatment. We used SEER data to investigate the role of radiation therapy (RT) in the management of this unusual cancer. Materials/Methods: The SEER database (National Cancer Institute) was queried using software for cases of small cell rectal cancer. Locoregional cases were defined using the “SEER Historic Stage A” variable to exclude patients with distant metastatic disease. Years of diagnosis were limited to 1988-2009 to reduce variability in staging criteria or longitudinal changes in surgery and radiation techniques. Two month conditional survival was applied to minimize bias by excluding patients who did not survive long enough to receive cancer-directed therapy. Overall survival was compared between patients who received RT (RT) and those who did not (No_RT) using the Kaplan-Meier method. Multivariate Cox proportional hazards model was used to evaluate important covariates, with AJCC Stage as a stratification variable. Case data were extracted and analyzed. Results: A total of 70 cases of locoregional small cell rectal cancer met the study criteria, No_RT Z 29 and RT Z 41. There were 23 deaths in each group. Median survival was significantly longer for patients who received radiation (RT 30 months vs No_RT 9 months, log-rank p Z 0.003). This corresponded to a higher 2-year overall survival rate for those who received radiation (56.8% vs 23.2%). Unadjusted hazard ratio for death (HR) was 0.43 with the use of radiation (95% CI, 0.24-0.76). Cox proportional hazards model (see Table) identified radiation therapy as the only significant factor for overall survival, multivariate HR Z 0.30 (95% CI, 0.150.62; p Z 0.001). Age, surgery and sex were not significant covariates. Conclusions: Small cell rectal cancer is a rare disease with no proven standard of care. Using the SEER data, we have identified a significant survival advantage with the use of radiation therapy. No survival benefit was seen with surgical resection, although this study lacked power to exclude small to moderate differences. Known limitations of the SEER data apply to this study, especially the lack of information on chemotherapy usage. Our findings strongly support the use of radiation therapy for patients with locoregional small cell rectal cancer. Author Disclosure: H.C. Hsu: None. C.G. Leichman: None. K.L. Du: None.

Prognostic Significance of Serum Carcinoembryonic Antigen Normalization on Survival in Rectal Cancer Treated with Preoperative Chemoradiation

PurposeThe purpose of this retrospective study was to identify factors predictive of survival in rectal cancer patients who received surgery with curative intent after preoperative chemoradiotherapy (CRT).Materials and MethodsBetween July 1996 and June 2010, 104 patients underwent surgery for rectal cancer after preoperative CRT. The median dose of radiotherapy was 50.4 Gy (range, 43.2 to 54.4 Gy) for 6 weeks. Chemotherapy was a bolus injection of 5-fluorouracil and leucovorin for the first and last week of radiotherapy (n=84, 77.1%) or capecitabine administered daily during radiotherapy (n=17, 16.3%). Low anterior resection (n=86, 82.7%) or abdominoperineal resection (n=18, 17.3%) was performed at a median 47 days from the end of radiotherapy, and four cycles of adjuvant chemotherapy was administered. The serum carcinoembryonic antigen (CEA) level was checked at initial diagnosis and just before surgery.ResultsAfter a median follow-up of 48 months (range, 9 to 174 months), 5-year disease free survival (DFS) was 74.5% and 5-year overall survival (OS) was 86.4%. Down staging of T diagnoses occurred in 32 patients (30.8%) and of N diagnoses in 40 patients (38.5%). The CEA change from initial diagnosis to pre-surgery (high-high vs. high-normal vs. normal-normal) was a statistically significant prognostic factor for DFS (p=0.012), OS (p=0.002), and distant metastasis free survival (p=0.018) in a multivariate analysis.ConclusionPatients who achieve normal CEA level by the time of surgery have a more favorable outcome than those who retain a high CEA level after preoperative CRT. The normalization of CEA levels can provide important information about the prognosis in rectal cancer treatment.

Prognostic Significance of Partial Tumor Regression After Preoperative Chemoradiotherapy for Rectal Cancer

Complete tumor regression after preoperative chemoradiotherapy for rectal cancer has been associated with better disease-free and overall survival. The survival experience for patients with partial tumor regression is less clear. The aim of this meta-analysis was to evaluate the prognostic significance of partial response after preoperative chemotherapy on disease-free survival in rectal cancer patients. Relevant studies were identified by a search of MEDLINE and EMBASE databases with no restrictions to October 31, 2012. We included long-course radiotherapy that reported the association between degree of tumor regression and disease-free survival of rectal cancer. Direct, indirect, and graph methods were used to extract HRs. Study-specific HRs on the disease-free survival were pooled using a random-effects model. Eleven articles in total were selected. Analysis was performed first among the 6 studies that separated partial response from the complete response and later among all 11 of the studies. Pooled HR was 0.49 (95% CI, 0.28-0.85) for the 6 studies that compared partial response with poor response. It was 0.41 (95% CI, 0.25-0.67) when all 11 of the studies were analyzed together. The studies were limited by not being prospective, randomized trials, and the tumor regression grades were not uniform. Partial tumor response is associated with a 50% improvement in disease-free survival and should be considered as a favorable prognostic factor.

Combined modality therapy: Is it necessary for everyone?

Survival and relapse in rectal cancer are intimately associated with disease stage. Although surgery remains the primary treatment modality for rectal cancer, its limitations as an isolated curative treatment are well recognized. Trimodality therapy combining surgery, chemotherapy, and radiation has improved local recurrence rates and survival in patients with advanced rectal tumors (T3/4) or those with nodal involvement (N1/2). With the broad application of trimodality therapy, concern for over-treatment in select groups of patients exists. Current investigations are now focused on identifying subsets of favorable-risk patients who may benefit from tailored therapy and reducing exposure to unnecessary treatment-related risk.

Relative Survival is an Adequate Estimate of Cancer-Specific Survival: Baseline Mortality-Adjusted 10-Year Survival of 771 Rectal Cancer Patients

The objective of the present investigation is to assess the baseline mortality-adjusted 10-year survival of rectal cancer patients. Ten-year survival was analyzed in 771 consecutive American Joint Committee on Cancer (AJCC) stage I-IV rectal cancer patients undergoing open resection between 1991 and 2008 using risk-adjusted Cox proportional hazard regression models adjusting for population-based baseline mortality. The median follow-up of patients alive was 8.8 years. The 10-year relative, overall, and cancer-specific survival were 66.5% [95% confidence interval (CI) 61.3-72.1], 48.7% (95% CI 44.9-52.8), and 66.4% (95% CI 62.5-70.5), respectively. In the entire patient sample (stage I-IV) 47.3% and in patients with stage I-III 33.6 % of all deaths were related to rectal cancer during the 10-year period. For patients with AJCC stage I rectal cancer, the 10-year overall survival was 96% and did not significantly differ from an average population after matching for gender, age, and calendar year (p = 0.151). For the more advanced tumor stages, however, survival was significantly impaired (p < 0.001). Retrospective investigations of survival after rectal cancer resection should adjust for baseline mortality because a large fraction of deaths is not cancer related. Stage I rectal cancer patients, compared to patients with more advanced disease stages, have a relative survival close to 100% and can thus be considered cured. Using this relative-survival approach, the real public health burden caused by rectal cancer can reliably be analyzed and reported.

A Novel Risk-Adjusted Nomogram for Rectal Cancer Surgery Outcomes

The circumferential resection margin is the primary determinant of local recurrence and a major factor in survival in rectal cancer. Neither chemotherapy nor chemoradiation compensates for a margin positive for cancer. To identify treatment-related factors associated with hospital margin-positive resection and to develop a tool that could be used by individual hospitals to assess their outcomes based on their unique mix of patient and tumor characteristics. Retrospective review of the National Cancer Data Base, 1998-2007. Community and academic/research hospitals. Individuals with histologically confirmed localized rectal/rectosigmoid adenocarcinoma. All individuals underwent radical resection for rectal cancer with or without neoadjuvant therapy. Rate of margin positivity determined and adjusted for patient- and tumor-related factors to calculate expected margin positivity per hospital. An observed to expected ratio was calculated based on patient- and tumor-related factors to identify treatment-associated variation. The overall margin-positive resection rate was 5.2%. Patients with margins positive for cancer were more likely to be older, male, and African American; not have private insurance; and have their cancer diagnosed later in the study period. Associated tumor-related factors include rectal location, higher American Joint Committee on Cancer stage, signet/mucinous histology, and poor/undifferentiated grade. Among hospitals that were significantly low outliers, 47% were comprehensive community hospitals, and 43.9% were academic/research hospitals; of those that were significantly high outliers, 52.3% were comprehensive community hospitals, and 17.8% were academic/research hospitals. High-volume centers made up 80% of significantly low outlier hospitals and 17% of significantly high outlier hospitals. The rates of chemotherapy and radiation were similar, but low outlier hospitals gave more neoadjuvant radiation (26.3% vs 17%). After adjustment for patient- and tumor-related factors, we identified both low and high outlier hospitals for margin positivity at resection, as well as potentially modifiable risk factors. The nomogram created in this model allows for the evaluation of observed and expected event rates for individual hospitals, providing a hospital self-assessment tool for identifying targets for improvement.

Colon and Rectal Cancer Survival by Tumor Location and Microsatellite Instability

Cancers in the proximal colon, distal colon, and rectum are frequently studied together; however, there are biological differences in cancers across these sites, particularly in the prevalence of microsatellite instability. We assessed the differences in survival by colon or rectal cancer site, considering the contribution of microsatellite instability to such differences. This is a population-based prospective cohort study for cancer survival. This study was conducted within the Colon Cancer Family Registry, an international consortium. Participants were identified from population-based cancer registries in the United States, Canada, and Australia. Information on tumor site, microsatellite instability, and survival after diagnosis was available for 3284 men and women diagnosed with incident invasive colon or rectal cancer between 1997 and 2002, with ages at diagnosis ranging from 18 to 74. Cox regression was used to calculate hazard ratios for the association between all-cause mortality and tumor location, overall and by microsatellite instability status. Distal colon (HR, 0.59; 95% CI, 0.49-0.71) and rectal cancers (HR, 0.68; 95% CI, 0.57-0.81) were associated with lower mortality than proximal colon cancer overall. Compared specifically with patients with proximal colon cancer exhibiting no/low microsatellite instability, patients with distal colon and rectal cancers experienced lower mortality, regardless of microsatellite instability status; patients with proximal colon cancer exhibiting high microsatellite instability had the lowest mortality. Study limitations include the absence of stage at diagnosis and cause-of-death information for all but a subset of study participants. Some patient groups defined jointly by tumor site and microsatellite instability status are subject to small numbers. Proximal colon cancer survival differs from survival for distal colon and rectal cancer in a manner apparently dependent on microsatellite instability status. These findings support the premise that proximal colon, distal colon, and rectal cancers are clinicopathologically distinct.

VEGFA, FLT1, KDR and colorectal cancer: Assessment of disease risk, tumor molecular phenotype, and survival

Angiogenesis is essential for tumor progression. Vascular endothelial growth factor (VEGFA) and its receptors 1 (FLT1) and 2 (KDR), have been identified as major mediators of this process. We hypothesized that genetic variation in FLT1 (38 SNPs), KDR (22 SNPS), and VEGFA (11 SNPs) would be associated with colon and rectal cancer development and survival. Data from a case-control study of 1555 colon cancer cases and 1956 controls and 754 rectal cancer cases and 959 controls were used. An adaptive rank truncation product (ARTP), based on 10,000 permutations, was used to determine the statistical significance of the candidate genes and angiogenesis pathway. Based on ARTP results, FLT1 was significantly associated with risk of colon cancer (P(ARTP) = 0.045) and VEGFA was significantly associated with rectal cancer (P(ARTP) = 0.036). After stratifying by tumor molecular subtype, SNP associations observed for colon cancer were: VEGFA rs2010963 with CIMP+ colon tumors; FLT1 rs4771249 and rs7987649 with TP53; FLT1 rs3751397, rs7337610, rs7987649, and rs9513008 and KDR rs10020464, rs11941492, and rs12498529 with MSI+ and CIMP+/KRAS2-mutated tumors. FLT1 rs2296189 and rs600640 were associated with CIMP+ rectal tumors and FLT1 rs7983774 was associated with TP53-mutated rectal tumors. Four SNPs in FLT1 were associated with colon cancer survival while three SNPs in KDR were associated with survival after diagnosis with rectal cancer. Aspirin/NSAID use, smoking cigarettes, and BMI modified the associations. These findings suggest the importance of inflammation and angiogenesis in the etiology of colorectal cancer and that genetic and lifestyle factors may be targets for modulating disease risk.

Multidisciplinary Approach to Rectal Cancer: Are we Ready for Selective Treatment Strategies?

With optimized local treatment, achieved in the last years by TME surgery and the shift from a postoperative to a preoperative treatment approach, distant metastases have become the predominant mode of failure in rectal cancer. Therefore, the intensification of chemotherapy seems essential to improve distant control and survival in rectal cancer. The integration of newer generation chemotherapeutics and target agents into fluoropyrimidines-based chemoradiotherapy (CRT) has been the more actively pursued intensification strategy. However, early results from randomized phase III trials, evaluating the addition of oxaliplatin to preoperative fluoropyrimidines-based CRT, did not show a significant impact on early pathological response with the addition of oxaliplatin, with the exception of the German CAO/ARO/AIO-04 study. Moreover, the integration of target agents into preoperative CRT, although attractive in principle, has yielded low rates of pathologic complete responses when combined with cetuximab and some concerns on surgical morbidity following preoperative treatment with bevacizumab have been raised. Several novel strategies with different sequence of multimodal treatment components have been developed. However, the evidence that rectal cancers are a widely heterogeneous group of tumors with different prognostic implications, has indicated that the careful assessment of the risk of recurrence is a critical issue. In the era of the preoperative approach, staging with MRI, for its ability to predict the involvement of the mesorectal fascia, should be mandatory for all patients with rectal cancer, to refine the selection of patients for different treatment strategies. Moreover, considering that response to preoperative treatment is not uniformly obtained in all patients and post-operative chemotherapy is generally met with poor adherence, a risk-adapted strategy should be pursued in the postoperative setting as well. The selection of patients for different multidisciplinary treatment strategies based on clinico-pathological features, rather than the current "one size fits all" approach, will allow minimizing therapy and maximizing outcome for rectal cancer patients.

Clinical, MRI, and PET-CT Criteria Used by Surgeons to Determine Suitability for Pelvic Exenteration Surgery for Recurrent Rectal Cancers

Surgical resection with clear margins is the major predictor of long-term survival in recurrent rectal cancer. The extent of pelvic exenteration surgery depends on many factors including clinical and radiological criteria. The aim of this study was to establish which clinical, MRI, and PET criteria were considered important by surgeons who perform pelvic exenteration surgery, when assessing a patient with recurrent rectal cancer for pelvic exenteration surgery. A 2-stage Delphi study was conducted among an international panel of 36 colorectal surgeons recruited via a snowball-sampling method. Surgeons rated the importance of 99 clinical and radiological criteria by using a 9-point scale. Consensus was attained when at least 85% of the panel rated criteria within 3 points. Clinical factors suggestive of systemic disease, symptoms of advanced local recurrence such as pain, surgical fitness, and cognitive impairment were considered important by the panel when considering suitability for surgery. Agreement regarding the indication for surgery was reached for 20 radiological factors. Strong agreement was achieved for factors associated with tumor involvement in the axial and anterior compartments. For only 16 of these 20 radiological factors was there an agreement that a clear resection margin was likely to be achieved. Further rounds of Delphi may have yielded greater consensus. This study has identified a set of criteria considered by experts to be important in evaluating patients' suitability for pelvic exenteration surgery. Evaluation of these criteria is required to determine their clinical utility in predicting a negative resection margin at pelvic exenteration surgery.

Multivisceral Resection in Colorectal Cancer: A Systematic Review

The objective of this study was to critically evaluate current literature on outcomes following multivisceral resection (MVR) in colorectal cancer (CRC). Adequate surgical resection with clear margins is imperative in achieving long-term survival in colorectal cancer. Where there is adherence to or invasion of adjacent organs, (MVR) may be needed to achieve complete disease clearance. A systematic review of MVR in CRC was performed. Pubmed/Medline and Cochrane databases were searched for English language articles from 1995 to 2012 using a predefined strategy. Retrieved abstracts were independently screened for relevance and data extracted from selected studies by 2 researchers. Results are reported as weighted means. Included were 22 studies comprising 1575 patients (87.0% primary colorectal cancer; 13.0% recurrent, 63.8% rectal; 36.2% colon). The most common organs resected were the bladder and reproductive organs. The perioperative mortality was 4.2% with morbidity of 41.5% (95% CI, 40.8-42.2%). The overall 5-year survival rate was 50.3% (95% CI, 49.9-50.8%). Surgery for recurrence was associated with worse outcomes than primary tumors with 5-year survival 19.5% (95% CI, 17.8-21.1%) for recurrent rectal cancer and primary rectal tumors 5-year overall survival 52.8% (95% CI, 52.0-53.8%). R0 resection was the strongest factor associated with long-term survival. Multivisceral resection provides the best possibility of long-term survival in locally advanced primary colorectal cancer in which a clear margin has been achieved.

Differential lymph node retrieval in rectal cancer: associated factors and effect on survival.

Recent publications have identified positive associations between numbers of lymph nodes pathologically examined and five-year overall survival (5-yr OS) in colon cancer. However, focused examinations of relationships between survival of rectal cancer and lymph node counts are less common. We conducted a single institution, retrospective review of rectal cancer resections to determine whether lymph node counts correlated with 5-yr OS and to explore the relationship between lymph node counts and various clinical and pathologic factors. A retrospective review of our institutional tumor registry identified 159 patients with AJCC Stage 1, 2, or 3 rectal cancers that underwent surgical resection at our institution over eleven years. Univariate analysis was used to explore the relationship between lymph node counts and age, AJCC Stage, time period of diagnosis, preoperative radiotherapy, and performance of TME. Survival analysis was performed by the Kaplan-Meier method and the Cox proportional hazards model. In univariate analysis, there was an association between increased lymph node counts and age <70, higher stage, and diagnosis during the later portion of the study period [all P-values <0.05]. Lymph node counts were not associated with survival in Kaplan-Meier analysis or in multivariate Cox proportional hazards analysis. Increasing lymph node counts improve survival and the accuracy of colorectal cancer staging. The body of literature recommends identical minimum lymph node counts in both colon and rectal cancer. In our study, which exclusively examined rectal cancer, we could not demonstrate that increased lymph node counts were associated with improved survival.

Pre-operative hypoalbuminaemia predicts poor overall survival in rectal cancer: a retrospective cohort analysis

BackgroundSerum albumin is a marker of nutrition and inflammation. It has recently emerged as a predictor of outcome after surgery for rectal cancer. Our aim was to evaluate if pre-operative serum albumin would predict survival after resection for rectal cancer.Method226 Patients with rectal cancer of all stages undergoing resection with curative intent were studied. Kaplan-Meier curves analysed survival based on a pre-operative albumin level of <35 g/L vs. >35 g/L. We sought for significant associations of survival with age, sex, stage, tumour site, use of neoadjuvant chemoradiation, microscopic positive resection margins, differentiation, angio, peri-neural, and lymphovascular invasion using individual variable analysis. Multifactorial analysis was performed using type III analysis with Weibull hazard model and Cox-proportional hazard model. Significance was assigned to a P value <0.05.ResultsOf 226 patients (median age- 59 years; range 19 – 88, Male - 54%), forty five (20%) had an albumin level < 35 g/L and was associated with a poor overall survival (P = 0.02). Mean survival in months for <35 g/L vs. >35 g/L was 64.7 (SE - 9.3) vs. 95.8 (SE – 7.0) and 5 year overall survival rates were 49% and 69%. Individual variable analysis revealed age, circumferential margin, stage, perineural, lympho-vascular and angio invasion to be also significant. With multifactorial analysis hypoalbuminaemia (HR = 0.58; 95% CI: 0.35 - 0.95, P = 0.03), advanced stage (HR = 2.0; 95% CI: 1.26 - 3.23, P < 0.01) and positive circumferential margin (HR = 2.2; 95% CI: 1.26 - 3.89, P < 0.01) remained significant.ConclusionPreoperative hypoalbuminaemia is an independent risk factor for poor overall survival in rectal cancer. Advanced tumour stage and circumferential margin positivity were the other associations with poor survival.

Abstract LB-321: Combination dendritic cell and conventional chemoradiation therapy improves survival for rectal cancer in a murine model.

Abstract The goal of neoadjuvant therapy in rectal cancer is to downstage or preferably eradicate the tumor prior to resection. Achieving complete pathologic response (CPR) using neoadjuvant chemoradiation is associated with improved overall and disease free survival. The aim of this study was to achieve improved complete pathologic response rates and survival by combining intra-tumoral injection of dendritic cells with conventional therapy. A syngeneic rectal cancer cell line (CT26) was subcutaneously injected into the thigh of immunocompetent Balb/c mice. Mice either received no treatment, conventional chemoradiation (CXRT) (5-fluorouracil + XRT) for 3 weeks, or CXRT plus tumor-lysate pulsed dendritic cells (CXRT/DC). Specific anti-CT26 cytotoxic T cell (CTL) activity was determined using standard chromium release assay. Flow cytometry for immune cell subsets was performed on cells isolated from spleens and tumors. Animals in the control group showed predictable uninhibited growth and all were euthanized due to tumor size. CXRT animals showed improved survival but none achieved complete response. Thirty three percent of the animals in CXRT/DC group exhibited CPR. Median survival for the control, CXRT, and CXRT/DC treated animals was 24, 46.5, 67 days, (p&amp;lt;0.0001). Splenocytes from CXRT/DC treated mice exhibited higher specific anti-CT26 CTL activity (28%) when compared to CXRT (17%), untreated control (11%) and naïve mice (&amp;lt;1%). Flow cytometry demonstrated an increase in regulatory T cells (Tregs), macrophages, granulocytic myeloid derived suppressor cells (MDSCs) and monocytic MDSCs in tumor bearing animals, (p&amp;lt;0.05). Dendritic cell activity stimulates anti-tumor CTL responses, but may also decrease MDSC and Treg mediated immunosuppression. Addition of dendritic cells to conventional chemoradiation therapy for rectal cancer increases complete pathologic response and thereby survival via immune modulation. Further analysis will allow subset comparisons between treatment groups. Citation Format: Swapnil D. Kachare, Jennifer M. Cayer, F. Melinda Carver, Zachary P. Englert, Kathryn M. Verbanac, Emmanuel E. Zervos, Nasreen A. Vohra. Combination dendritic cell and conventional chemoradiation therapy improves survival for rectal cancer in a murine model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-321. doi:10.1158/1538-7445.AM2013-LB-321

Interdisziplinäre, primäre Rekonstruktion des Perineums zur Vermeidung von Wundkomplikationen nach abdominoperinealer Rektumexstirpation

Multimodal treatment options for ultra-low neoplasms of the rectum or anal cancer include chemotherapy, radical abdominoperineal resection and/or radiation. Primary wound closure increases the risk of perineal wound complications that require secondary revision. Perineal wound complications may trigger delay of adjacent tumor therapy and thus have an impact on rate of local recurrence and long-term survival for rectal cancer. Simultaneous primary reconstruction of the perineal defect has been shown to reduce the incidence of perineal wound complications as well as hospital stay which enables timely adjacent therapy and may improve prognosis. This study was designed to retrospectively evaluate wound complications after abdominoperineal resection by comparing a group with and one without primary perineal reconstruction. Between 2005 and 2011, patients were analysed and divided into cohorts 1 and 2. Cohort 1 included n = 33 patients without primary perineal reconstruction. Cohort 2 included n = 4 patients with primary perineal reconstruction. Risk factors were identified for increased wound complications and delay of adjacent therapy. Subgroup analysis revealed that 18 out of 33 patients of cohort 1 had wound complications. In five cases, prolonged wound healing resulted in a delay of adjacent therapies. Four patients suffered from progression of tumour, 2 out of these 4 patients had a history of delayed adjacent therapy. The main risk factor for prolonged wound healing due to postoperative complications was a history of neoadjuvant treatment resulting in a rate of 64.7 %. Cohort 2 undergoing primary reconstruction presented without wound complications or delay in adjuvant therapy. A primary perineal reconstruction after APRE can reduce the rate of perineal wound complications. Furthermore, neoadjuvant treatment was shown to carry a major risk for wound complications. Patients after radio-/chemotherapy should undergo a primary reconstruction to prevent procedure-related perioperative morbidity. Subsequently, delays in adjuvant therapy, and prolonged hospital stay can be inhibited. Moreover, quality of life can be increased. The interdisciplinary approach aims at identifying high-risk patients for perineal wound complications who may benefit from primary reconstruction in order to reduce rate of wound complications with potential impact on rate of local recurrence. All these measures contribute to an optimized surgical standard.

Altered PTEN function caused by deletion or gene disruption is associated with poor prognosis in rectal but not in colon cancer

Colorectal cancer is the third most common malignancy worldwide. Anti-epidermal growth factor receptor (EGFR)-targeted therapy shows clinical evidence in this malignancy and improves outcome. The tumor suppressor gene phosphatase and tensin homologue (PTEN) is considered a potential predictor of nonresponse to anti-EGFR agents. The purpose of this study was to assess whether associations between PTEN alterations (PTEN gene deletion or PTEN gene disruption) and clinical outcome could be caused by a prognostic (and not predictive) effect of PTEN inactivation. Therefore, we analyzed 404 colorectal cancers not previously treated with anti-EGFR drugs in a tissue microarray format. PTEN deletion and PTEN gene rearrangements were analyzed by fluorescence in situ hybridization. Heterogeneity analysis of all available large tissue sections was performed in 6 cases with genomic PTEN alteration. Twenty-seven (8.8%) of 307 analyzable colorectal cancer spots showed genomic PTEN alterations including 24 hemizygous and 1 homozygous deletion as well as 2 PTEN gene disruptions. Genomic PTEN alterations were associated with reduced patient survival in rectal cancer in univariate and multivariate analyses (P = .012; hazard ratio, 2.675; 95% confidence interval, 1.242-5.759) but not in colon cancer. Large-section evaluation revealed a homogeneous distribution pattern in all 4 analyzed cases with PTEN deletion and in both cases with a PTEN gene disruption. In conclusion, genomic PTEN gene alterations caused by deletion or gene disruption characterize a fraction of rectal cancers with particularly poor outcome.

Surgical practice patterns and long-term survival for early-stage rectal cancer.

459 Background: Local excision (LE) is considered a standard option only for patients with T1N0 rectal cancer and those who are medically unfit for proctectomy. The growing numbers of case series suggest that use of LE may be increasing. The objectives of this study are to characterize practice patterns for surgical management of rectal cancer and determine the comparative effectiveness of LE versus proctectomy for overall survival (OS) for Stage I rectal cancer. Methods: National Cancer Database data were used to identify all patients with rectal cancer diagnosed from 1998-2010. Patient and tumor characteristics associated with procedure type were examined. Kaplan-Meier plots and Cox proportional hazards models, controlling for patient and tumor characteristics and receipt of radiation (XRT), were used to compare OS for Stage I cases from 1998-2005. Results: 147,553 (50%) of 296,068 cases were excluded due to prior malignancy, non-invasive disease, distant metastases, failure to receive definitive surgery, treatment indicated to be palliative, or receipt of neoadjuvant therapy. 76,756 (69%) cases were treated with proctectomy and 34,697 (31%) with LE. Use of LE steadily increased from 23% in 1998 to 41% in 2010, p&lt;0.001. LE was most commonly used for Stage I cases. Women, older patients, patients with less comorbidities, black patients, uninsured patients, and those with T1 tumors were more likely to receive LE than other Stage I patients. Socioeconomic status and rurality were not associated with use of LE. Adjuvant XRT was used for 12% of T1 tumors and 46% of T2 tumors after LE and 5% of T1 tumors and 12% of T2 tumors after proctectomy. For patients with T1N0 tumors, adjusted OS was associated with receipt of proctectomy (HR 0.83; 95%CI 0.77, 0.89) but not XRT. For patients with T2N0 tumors, adjusted OS was associated with both proctectomy and XRT: LE only HR 1.0; proctectomy only HR 0.70; LE+XRT HR 0.70; proctectomy+XRT HR 0.70. Conclusions: Use of LE for rectal cancer is increasing. LE alone is associated with poorer long-term OS than proctectomy. For patients with larger tumors, those that receive adjuvant XRT in addition to LE have significantly better OS than those who receive LE alone.

Prognostic markers of time to local recurrence and overall survival in early-stage rectal cancer.

473 Background: Surgical resection without adjuvant therapy results in a low recurrence rate for patients with early stage (i.e. T1-2 N0) rectal cancer, in the range of 4-15% at 5 years. There are limited data regarding clinical or pathologic markers that are prognostic for recurrence in this population. This study assesses factors associated with time to local recurrence (TTLR) and overall survival (OS) in these patients. Methods: From 2000 to 2008, 177 patients with stage I rectal cancer treated with surgery alone were identified. Data were retrospectively reviewed to identify markers associated with TTLR and OS, including staging method, preoperative CEA, type of surgery, tumor size, lymph node resection, histological grade, circumferential resection margin, and presence of lymphovascular invasion (LVI), lymphocytic infiltration, or ulceration on pathology. Data were analyzed using a Cox proportional hazards regression model. Results: Of the eligible cohort, 137 patients had complete follow up data for analysis of TTLR, and 23 (16.8%) locally recurred. Among these 23 patients, the median TTLR was 1.1 years (0.1-7.8). On univariate analysis, male gender, current alcohol use, LVI and tumor ulceration were associated with heightened risk for LR, and male gender (HR 3.3, p=0.02), current alcohol use (HR 3.4, p=0.01) and tumor ulceration (HR 4.2, p=0.001) remained statistically significant on multivariate analysis. Of the original cohort, 173 patients had complete follow up for OS analysis. Among these patients, the median OS was 12 years. On univariate analysis, age at diagnosis &gt; 65 years, T2 pathologic stage, and tumor size &gt; 4.5 cm were associated with decreased OS, and age at diagnosis &gt; 65 years (HR 2.1, p=0.04) and T2 pathologic stage (HR 2.5, p=0.008) were predictors of reduced OS on multivariate analysis. Conclusions: For patients with stage I rectal cancer treated with surgery alone, male gender, current alcohol use, and tumor ulceration are poor prognostic markers for TTLR. Within this population, age at diagnosis &gt; 65 years and T2 pathologic stage are predictive for reduced OS. These results provide important prognostic information for patients and may help identify those who could benefit from additional therapy.

Prognostic Impact of the Metastatic Lymph Node Ratio on Survival in Rectal Cancer

PurposeLymph-node metastasis is the most important predictor of survival in stage III rectal cancer. The number of metastatic lymph nodes may vary depending on the level of specimen dissection and the total number of lymph nodes harvested. The aim of this study was to evaluate whether the lymph node ratio (LNR) is a prognostic parameter for patients with rectal cancer.MethodsA retrospective review of a database of rectal cancer patients was performed to determine the effect of the LNR on the disease-free survival (DFS) and the overall survival. Of the total 228 patients with rectal cancer, 55 patients with stage III cancer were eligible for analysis. Survival curves were estimated using the Kaplan-Meier method. Cox regression analyses, after adjustments for potential confounders, were used to evaluate the relationship between the LNR and survival.ResultsAccording to the cutoff point 0.15 (15%), the 2-year DFS was 95.2% among patients with a LNR < 0.15 compared with 67.6% for those with LNR ≥ 0.15 (P = 0.02). In stratified and multivariate analyses adjusted for age, gender, histology and tumor status, a higher LNR was independently associated with worse DFS.ConclusionThis study showed the prognostic significance of ratio-based staging for rectal cancer and may help in developing better staging systems. LNR 0.15 (15%) was shown to be a cutoff point for determining survival and prognosis in rectal cancer cases.

Colon and Rectal Cancer Survival by Tumor Location and Microsatellite Instability: The Colon Cancer Family Registry

Colon and Rectal Cancer Survival by Tumor Location and Microsatellite Instability: The Colon Cancer Family Registry