NCCN Guidelines® Insights: Rectal Cancer, Version 3.2024.

The determination of an optimal treatment plan for an individual patient with rectal cancer is a complex process. In addition to decisions relating to the intent of rectal cancer surgery (ie, curative or palliative), consideration must also be given to the likely functional results of treatment, including the probability of maintaining or restoring normal bowel function/anal continence and preserving genitourinary functions. Particularly for patients with distal rectal cancer, finding a balance between curative-intent therapy while having minimal impact on quality of life can be challenging. Furthermore, the risk of pelvic recurrence is higher in patients with rectal cancer compared with those with colon cancer, and locally recurrent rectal cancer is associated with a poor prognosis. Careful patient selection and the use of sequenced multimodality therapy following a multidisciplinary approach is recommended. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Rectal Cancer, including the addition of endoscopic submucosal dissection as an option for early-stage rectal cancer, updates to the total neoadjuvant therapy approach based on the results of recent clinical trials, and the addition of a "watch-and-wait" nonoperative management approach for clinical complete responders to neoadjuvant therapy.

Colon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States. Management of disseminated metastatic CRC involves various active drugs, either in combination or as single agents. The choice of therapy is based on consideration of the goals of therapy, the type and timing of prior therapy, the mutational profile of the tumor, and the differing toxicity profiles of the constituent drugs. This manuscript summarizes the data supporting the systemic therapy options recommended for metastatic CRC in the NCCN Guidelines for Colon Cancer.

Anal Carcinoma, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

This discussion summarizes the NCCN Clinical Practice Guidelines for managing squamous cell anal carcinoma, which represents the most common histologic form of the disease. A multidisciplinary approach including physicians from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology is necessary. Primary treatment of perianal cancer and anal canal cancer are similar and include chemoradiation in most cases. Follow-up clinical evaluations are recommended for all patients with anal carcinoma because additional curative-intent treatment is possible. Biopsy-proven evidence of locally recurrent or persistent disease after primary treatment may require surgical treatment. Systemic therapy is generally recommended for extrapelvic metastatic disease. Recent updates to the NCCN Guidelines for Anal Carcinoma include staging classification updates based on the 9th edition of the AJCC Staging System and updates to the systemic therapy recommendations based on new data that better define optimal treatment of patients with metastatic anal carcinoma.

Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Rectal Cancer focuses on management of malignant polyps and resectable nonmetastatic rectal cancer because important updates have been made to these guidelines. These recent updates include redrawing the algorithms for stage II and III disease to reflect new data supporting the increasingly prominent role of total neoadjuvant therapy, expanded recommendations for short-course radiation therapy techniques, and new recommendations for a "watch-and-wait" nonoperative management technique for patients with cancer that shows a complete response to neoadjuvant therapy. The complete version of the NCCN Guidelines for Rectal Cancer, available online at NCCN.org, covers additional topics including risk assessment, pathology and staging, management of metastatic disease, posttreatment surveillance, treatment of recurrent disease, and survivorship.

Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation-positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org. Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.

NCCN Guidelines Insights: Rectal Cancer, Version 6.2020.

The NCCN Guidelines for Rectal Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with rectal cancer. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines. These updates include clarifying the definition of rectum and differentiating the rectum from the sigmoid colon; the total neoadjuvant therapy approach for localized rectal cancer; and biomarker-targeted therapy for metastatic colorectal cancer, with a focus on new treatment options for patients with BRAF V600E- or HER2 amplification-positive disease.

Pathologic Complete Response Despite Nodal Yield Has Best Survival in Locally Advanced Rectal Cancer.

BACKGROUND: Controversy exists regarding the ability of neoadjuvant chemoradiation (nCR) to diminish lymph node yield (LNY) and how that relationship is influenced by tumor response in patients undergoing proctectomy for locally advanced rectal cancer. MATERIALS AND METHODS: The National Cancer Database was used to identify patients with rectal adenocarcinomas from 2004 to 2014. Patients that received nCR were compared with those that underwent surgery alone. LNY was stratified into <12 and ≥12 groups to determine their differences in stage specific overall survival. RESULTS: Of 56,812 patients 46.5% underwent surgery alone and 53.5% were administered nCR. There were more patients with LNY<12 in the nCR group compared to surgery alone, across all stages (44.1% versus 36.5%, P < 0.001). nCR improved OS regardless of LNY (P < 0.001). Although patients with LNY≥12 had improved overall survival, patients who had a pathologic complete response (pCR) achieved the greatest survival. In patients that did not achieve a pCR, LNY≥12 was a marker of improved OS but LNY did not impact OS in patients that attained pCR (P < 0.001). CONCLUSIONS: Although nCR diminished LNY, LNY≥12 improved OS demonstrating the importance of quality total mesorectal excision. However, LNY did not impact patients that achieved pCR. These patients, who achieved the best OS, demonstrated that tumors' biologic response to nCR had the greatest impact on patient outcomes.

Small Bowel Adenocarcinoma, Version 1.2020, NCCN Clinical Practice Guidelines in Oncology.

Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract that has increased in incidence across recent years. Often diagnosed at an advanced stage, outcomes for SBA are worse on average than for other related malignancies, including colorectal cancer. Due to the rarity of this disease, few studies have been done to direct optimal treatment, although recent data have shown that SBA responds to treatment differently than colorectal cancer, necessitating a separate approach to treatment. The NCCN Guidelines for Small Bowel Adenocarcinoma were created to establish an evidence-based standard of care for patients with SBA. These guidelines provide recommendations on the workup of suspected SBA, primary treatment options, adjuvant treatment, surveillance, and systemic therapy for metastatic disease. Additionally, principles of imaging and endoscopy, pathologic review, surgery, radiation therapy, and survivorship are described.

Enhanced Recovery After Surgery for Noncolorectal Surgery?: A Systematic Review and Meta-analysis of Major Abdominal Surgery.

OBJECTIVE: To evaluate the impact of enhanced recovery after surgery (ERAS) protocols across noncolorectal abdominal surgical procedures. BACKGROUND: ERAS programs have been studied extensively in colorectal surgery and adopted at many centers. Several studies testing such protocols have shown promising results in improving postoperative outcomes across various surgical procedures. However, surgeons performing major abdominal procedures have been slower to adopt these ERAS protocols. METHODS: A systematic review was performed using "enhanced recovery after surgery" or "fast track" as search terms and excluded studies of colorectal procedures. Primary endpoints for the meta-analysis include length of stay (LOS) and complication rate. Secondary endpoints were time to first flatus, readmission rate, and costs. RESULTS: A total of 39 studies (6511 patients) met inclusion and exclusion criteria. Among them 14 studies were randomized trials, and the remaining 25 studies were cohort studies. Meta-analysis showed a decrease in LOS of 2.5 days (95% confidence interval, CI: 1.8-3.2, P < 0.001) and a complication rate of 0.70 (95% CI: 0.56-0.86, P = 0.001) for patient treated in ERAS programs. There was also a significant reduction in time to first flatus of 0.8 days (95% CI: 0.4-1.1, P < 0.001) and cost reduction of $5109.10 (95% CI: $4365.80-$5852.40, P < 0.001). There was no significant increase in readmission rate (OR 1.03, 95% CI: 0.84-1.26, P = 0.80) in our analysis. CONCLUSIONS: ERAS protocols decreased length of stay and cost by not increasing complications or readmission rates. This study adds to the evidence that ERAS protocols are safe to implement and are beneficial to surgical patients and the healthcare system across multiple abdominal procedures.

Anal Carcinoma, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Guidelines for Anal Carcinoma provide recommendations for the management of patients with squamous cell carcinoma of the anal canal or perianal region. Primary treatment of anal cancer usually includes chemoradiation, although certain lesions can be treated with margin-negative local excision alone. Disease surveillance is recommended for all patients with anal carcinoma because additional curative-intent treatment is possible. A multidisciplinary approach including physicians from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology is essential for optimal patient care.

Rectal Cancer, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Rectal Cancer address diagnosis, staging, surgical management, perioperative treatment, management of recurrent and metastatic disease, disease surveillance, and survivorship in patients with rectal cancer. This portion of the guidelines focuses on the management of localized disease, which involves careful patient selection for curative-intent treatment options that sequence multimodality therapy usually comprised of chemotherapy, radiation, and surgical resection.

NCCN Guidelines Insights: Colon Cancer, Version 2.2018.

The NCCN Guidelines for Colon Cancer provide recommendations regarding diagnosis, pathologic staging, surgical management, perioperative treatment, surveillance, management of recurrent and metastatic disease, and survivorship. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel discussions for the 2018 update of the guidelines regarding risk stratification and adjuvant treatment for patients with stage III colon cancer, and treatment of BRAF V600E mutation-positive metastatic colorectal cancer with regimens containing vemurafenib.

Does neoadjuvant/perioperative chemotherapy improve overall survival for T2N0 gastric adenocarcinoma?

BACKGROUND: The purpose of this study was to determine whether neoadjuvant and/or perioperative chemotherapy (NAC) has an overall survival (OS) benefit for patients with T2N0 gastric adenocarcinoma. STUDY DESIGN: We performed retrospective analyses using the National Cancer Data Base, 2004-2013. Patients with T2N0 gastric adenocarcinoma were divided into two treatment groups: (1) NAC plus surgery (NA + S) and (2) surgery alone (S). RESULTS: Of 1,704 patients included, 277 (16.3%) received NAC, and 1,427 (83.7%) were treated with surgery alone. Patients in the NA + S group were more likely to be younger, have fewer comorbidities, and have larger tumors located in the proximal stomach. Although in an unadjusted analysis of OS, the NA + S group had improved survival compared to the S group (HR = 0.81, 95% CI 0.67-0.99, P < 0.0001), this was not maintained in a propensity adjusted analysis (HR = 0.89, 95% CI 0.68-1.18, P = 0.42). Similarly, propensity adjusted analyses accounting for potential bias from clinical misstaging or treatment effect from NAC did not show any OS benefit from NAC. CONCLUSION: Based on the largest cohort of clinically staged T2N0 gastric adenocarcinoma, there was no OS benefit derived from NAC compared to surgery alone. For select patients with reliable preoperative staging, NAC may be omitted.

Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology.

This portion of the NCCN Guidelines for Colon Cancer focuses on the use of systemic therapy in metastatic disease. Considerations for treatment selection among 32 different monotherapies and combination regimens in up to 7 lines of therapy have included treatment history, extent of disease, goals of treatment, the efficacy and toxicity profiles of the regimens, KRAS/NRAS mutational status, and patient comorbidities and preferences. Location of the primary tumor, the BRAF mutation status, and tumor microsatellite stability should also be considered in treatment decisions.

National disparities in minimally invasive surgery for pancreatic tumors.

BACKGROUND: For patients with pancreatic tumors, several disparities have been shown to impact access to care, including surgery, and subsequently adversely affect long-term oncologic outcomes. The aim of this study was to investigate national disparities in minimally invasive surgery (MIS) across different demographics for pancreatic tumors. METHODS: We utilized the American College of Surgeons (ACS) National Cancer Data Base (NCDB) to identify patients with pancreatic tumors from 2010 to 2011 who had undergone surgery through either an open or MIS approach. Multivariable analysis was performed to investigate differences in patient characteristics in relation to surgical approach and conversion to open. RESULTS: A total of 2809 patients were identified. The initial surgical approach included 86.5 % open (2430) and 13.5 % MIS (87.6 % were laparoscopic, and 12.4 % were robotic). Tumor histology was significantly associated with MIS, whereby patients with neuroendocrine tumors were more than twice as likely to have an MIS approach compared to adenocarcinoma. Tumor location within the pancreas was also associated with MIS, with tumors in the tail being three times more likely to be removed through MIS compared to tumors in the head. For patients with disease in the body or tail of the pancreas, ethnicity was independently associated with MIS whereby patients of Hispanic origin were less likely to have MIS. The conversion rate to open was 27.7 %, and geographic location was associated with conversion rates. CONCLUSIONS: MIS procedures comprise approximately 13.5 % of surgical procedures for pancreatic tumors. In addition to tumor histology, differences in surgical approach were identified with respect to ethnicity for patients with tumors in the body/tail of the pancreas.

Does adjuvant therapy improve overall survival for stage IA/B pancreatic adenocarcinoma?

BACKGROUND: Current guidelines recommend adjuvant chemotherapy for resected pancreatic adenocarcinoma (PDAC). However, no studies have addressed its survival benefit for stage I patients as they comprise <10% of PDAC. METHODS: Using the NCDB 2006-2012, resected PDAC patients with stage I disease who received adjuvant therapy (chemotherapy or chemoradiation) were analyzed. Factors associated with overall survival (OS) were identified. RESULTS: 3909 patients with resected stage IA or IB PDAC were identified. Median OS was 60.3 months (mo) for stage IA and 36.9 mo for IB. 45.5% received adjuvant chemotherapy; 19.9% received adjuvant chemoradiation. There was OS benefit for both stage IA/IB patients with adjuvant chemotherapy (HR = 0.73 and 0.76 for IA and IB, respectively, p = 0.002 and <0.001). For patients with Stage IA disease (n = 1,477, 37.8%), age ≥70 (p < 0.001), higher grade (p < 0.001), ≤10 lymph nodes examined (p = 0.008), positive margins (p < 0.001), and receipt of adjuvant chemoradiation (p = 0.002) were associated with worse OS. For stage IB patients (n = 2,432, 62.2%), similar associations were observed with the exception of adjuvant chemoradiation whereby there was no significant association (p = 0.35). CONCLUSION: Adjuvant chemotherapy was associated with an OS benefit for patients with stage I PDAC; adjuvant chemoradiation was either of no benefit or associated with worse OS.

Predictors of Pathologic Complete Response Following Neoadjuvant Chemoradiotherapy for Rectal Cancer.

BACKGROUND: Some patients with rectal cancer who receive neoadjuvant chemoradiotherapy (nCRT) achieve a pathologic complete response (pCR) and may be eligible for less radical surgery or non-operative management. The aim of this study was to identify variables that predict pCR after nCRT for rectal cancer and to examine the impact of pCR on postoperative complications. METHODS: A retrospective review was performed of the NCDB from 2006 to 2011. Patients with rectal cancer who received nCRT followed by radical resection were included in this study. Multivariable analysis of the association between clinicopathologic characteristics and pCR was performed, and propensity-adjusted analysis was used to identify differences in postoperative morbidity between pCR and non-pCR patients. RESULTS: A total of 23,747 patients were included in the study. Factors associated with pCR included lower tumor grade, lower clinical T and N stage, higher radiation dose, and delaying surgery by more than 6-8 weeks after the end of radiation, while lack of health insurance was linked with a lower likelihood of pCR. Complete response was not associated with an increased risk of major postoperative complications. CONCLUSIONS: Several clinical, pathologic, and treatment variables can help to predict which patients are most likely to have pCR after nCRT for rectal cancer. Awareness of these variables can be valuable in counseling patients regarding prognosis and treatment options.

National disparities in minimally invasive surgery for rectal cancer.

BACKGROUND: Social and racial disparities have been identified as factors contributing to differences in access to care and oncologic outcomes in patients with colorectal cancer. The aim of this study was to investigate national disparities in minimally invasive surgery (MIS), both laparoscopic and robotic, across different racial, socioeconomic and geographic populations of patients with rectal cancer. METHODS: We utilized the American College of Surgeons National Cancer Database to identify patients with rectal cancer from 2004 to 2011 who had undergone definitive surgical procedures through either an open, laparoscopic or robotic approach. Inclusion criteria included only one malignancy and no adjuvant therapy. Multivariate analysis was performed to investigate differences in age, gender, race, income, education, insurance coverage, geographic setting and hospital type in relation to the surgical approach. RESULTS: A total of 8633 patients were identified. The initial surgical approach included 46.5% open (4016), 50.9% laparoscopic (4393) and 2.6% robotic (224). In evaluating type of insurance coverage, patients with private insurance were most likely to undergo laparoscopic surgery [OR (odds ratio) 1.637, 95% CI 1.178-2.275], although there was a less statistically significant association with robotic surgery (OR 2.167, 95% CI 0.663-7.087). Patients who had incomes greater than $46,000 and received treatment at an academic center were more likely to undergo MIS (either laparoscopic or robotic). Race, education and geographic setting were not statistically significant characteristics for surgical approach in patients with rectal cancer. CONCLUSIONS: Minimally invasive approaches for rectal cancer comprise approximately 53% of surgical procedures in patients not treated with adjuvant therapy. Robotics is associated with patients who have higher incomes and private insurance and undergo surgery in academic centers.