Current Management of Early and Advanced Rectal Cancer

Background: Extralevator abdominoperineal excision (ELAPE) is a relatively new surgical technique for low rectal cancers, enabling a more radical approach than conventional abdominoperineal excision (APE) with a potentially better oncological outcome. To date, no standard exists for reconstruction after extended or extralevator approaches of abdominoperineal (ELAPE) resection for lower gastrointestinal cancer or inflammatory tumors. In the recent literature, techniques with myocutaneous flaps, such as the VY gluteal flap, the pedicled gracilis flap, or the pedicled rectus abdominis flaps (VRAM) are primarily described. We propose a tailored concept with the use of bilateral adipo-fasciocutaneous inferior gluteal artery perforator (IGAP) advancement flaps in VY fashion after ELAPE surgery procedures. This retrospective cohort study analyzes the feasibility of this concept and is, to our knowledge, one of the largest published series of IGAP flaps in the context of primary closure after ELAPE procedures. Methods: In a retrospective cohort analysis, we evaluated all the consecutive patients with rectal resections from Jan 2017 to Sep 2021. All the patients with abdominoperineal resection were included in the study evaluation. The primary endpoint of the study was the proportion of plastic reconstruction and inpatient discharge. Results: Out of a total of 560 patients with rectal resections, 101 consecutive patients with ELAPE met the inclusion criteria and were included in the study evaluation. The primary direct defect closure was performed in 72 patients (71.3%). In 29 patients (28.7%), the defect was closed with primary unilateral or bilateral IGAP flaps in VY fashion. The patients’ mean age was 59.4 years with a range of 25–85 years. In 84 patients, the indication of the operation was lower rectal cancer or anal cancer recurrence, and non-oncological resections were performed in 17 patients. Surgery was performed in a minimally invasive abdominal approach in combination with open perineal extralevatoric abdominoperineal resection (ELAPE) and immediate IGAP flap reconstruction. The rate of perineal early complications after plastic reconstruction was 19.0%, which needed local revision due to local infection. All these interventions were conducted under general anesthesia (Clavien–Dindo IIIb). The mean length of the hospital stay was 14.4 days after ELAPE, ranging from 3 to 53 days. Conclusions: Since radical resection with a broad margin is the standard choice in primary, sphincter-infiltrating rectal cancer and recurrent anal cancer surgery in combination with ELAPE, the choice technique for pelvic floor reconstruction is under debate and there is no consensus. Using IGAP flaps is a reliable, technical, easy, and safe option, especially in wider defects on the pelvic floor with minimal donor site morbidity and an acceptable complication (no flap necrosis) rate. The data for hernia incidence in the long term are not known. Full article

Background: The adequate distal resection margin is still controversial in rectal cancer treated by neoadjuvant chemoradiotherapy (nCRT). The aim of this study was to assess the impact of a distal margin of ≤1 mm on locoregional recurrence-free survival (LRRFS). Methods: Among 255 patients treated with nCRT and surgery at the National Cancer Institute of Milan, 83 (32.5%) had a distal margin of ≤1 mm and 172 (67.5%) had a distal margin of >1 mm. Survival analyses were performed to assess the impact of distal margin on 5-year LRRFS, as well as Cox survival analysis. The role of distal margin on survival was analyzed according to different tumor regression grades (TRGs). Results: The overall 5-year LRRFS rate was 77.6% with a distal margin of ≤1 mm vs. 88.3% with a distal margin of >1 mm (Log-rank p = 0.09). Only stage ypT4 was an independent predictor of worse LRRFS (HR 15.14, p = 0.026). The 5-year LRRFS was significantly lower in TRG3–5 patients with a distal margin of ≤1 mm compared to those with a distal margin of >1 mm (68.5% vs. 84.2%, p = 0.027), while no difference was observed in case of TRG1–2 (p = 0.77). Conclusions: Low-responder rectal cancers after nCRT still require a distal margin of >1 mm to reduce the high likelihood of local relapse. Full article

Early postoperative low compliance to enhanced recovery protocols has been associated with morbidity following colon surgery. The purpose of this study is to evaluate the possible causes of early postoperative low compliance to the enhanced recovery pathway and its relationship with morbidity following rectal surgery for cancer. A total of 439 consecutive patients who underwent elective surgery for rectal cancer have been included in the study. Compliance to enhanced recovery protocol on postoperative day (POD) 2 was evaluated in all patients. Indicators of compliance were naso-gastric tube and urinary catheter removal, recovery of both oral feeding and mobilization, and the stopping of intravenous fluids. Low compliance on POD 2 was defined as non- adherence to two or more items. One-third of patients had low compliance on POD 2. Removal of urinary catheter, intravenous fluids stop, and mobilization were the items with lowest adherence. Advanced age, duration of surgery, open surgery and diverting stoma were predictive factors of low compliance at multivariate analysis. Overall morbidity and major complications were significantly higher (p < 0.001) in patients with low compliance on POD 2. At multivariate analysis, failure to remove urinary catheter on POD 2 (OR = 1.83) was significantly correlated with postoperative complications. Low compliance to enhanced recovery protocol on POD 2 was significantly associated with morbidity. Failure to remove the urinary catheter was the most predictive indicator. Advanced age, long procedure, open surgery and diverting stoma were independent predictive factors of low compliance. Full article

The perioperative and short-term oncological outcomes of robotic-assisted rectal surgery (RRS) are unclear. This retrospective observational study enrolled patients with rectal adenocarcinoma undergoing RRS from three high-volume institutions in Taiwan. Of the 605 enrolled patients, 301 (49.75%), 176 (29.09%), and 116 (19.17%) had lower, middle, and upper rectal cancers, respectively. Low anterior resection (377, 62.31%) was the most frequent surgical procedure. Intraoperative blood transfusion was performed in 10 patients (2%). The surgery was converted to an open one for one patient (0.2%), and ten (1.7%) patients underwent reoperation. The overall complication rate was 14.5%, including 3% from anastomosis leakage. No deaths occurred during surgery and within 30 days postoperatively. The positive rates of distal resection margin and circumferential resection margin were observed in 21 (3.5%) and 30 (5.0%) patients, respectively. The 5-year overall and disease-free survival rates for patients with stage I–III rectal cancer were 91.1% and 86.3%, respectively. This is the first multi-institutional study in Taiwan with 605 patients from three high-volume hospitals. The overall surgical and oncological outcomes were equivalent or superior to those estimated in other studies. Hence, RRS is an effective and safe technique for rectal resection in high-volume hospitals. Full article

We assessed the exact role of adjuvant chemotherapy after neoadjuvant chemoradiotherapy (CRT) and surgery in rectal cancer patients with positive surgical margin or perineural invasion (PNI). This multi-institutional study included 1799 patients with rectal cancer at cT3-4N0-2M0 stages. Patients were divided into two groups. The high-risk group had a positive margin and/or perineural invasion. The low-risk group showed no positive margin or PNI. Propensity-score matching analysis was performed, and a total of 928 patients, with 464 in each arm, were evaluated. The high-risk group showed significant differences in overall survival (OS, 73.4% vs. 53.9%, p < 0.01) and recurrence-free survival (RFS, 52.7% vs. 40.9%, p = 0.01) at five years between the adjuvant chemotherapy arm and observation arm. The low-risk group showed no significant differences in 5-year OS (p = 0.61) and RFS (p = 0.75) between the two arms. Multivariate analyses showed that age, pathologic N stage, and adjuvant chemotherapy were significantly correlated with OS and RFS in the high-risk group (all p < 0.05). Adjuvant chemotherapy improved OS and RFS more significantly in rectal cancer patients with positive surgical margin or PNI than in those with negative surgical margin and PNI. Full article

Aims: Between 11 to 14% of patients with locally advanced rectal cancer (LARC) have positive lateral pelvic lymph nodes (LPLN) at diagnosis, related to a worse prognosis with a 5-year survival rate between 30 to 40%. The best treatment choice for this group of patients is still a challenge. The optimal radiotherapy (RT) dose for LPLN patients has been investigated. Methods: We retrospectively collected data from LARC patients with LPLN at the primary staging MRI, treated in our center from March 2003 to December 2020. Patients underwent a neoadjuvant concomitant chemo-radiotherapy (CRT) treatment on the primary tumor (T), mesorectum, and pelvic nodes, associated with a fluoride-based chemotherapy. The total reached dose was 45 Gy at 1.8 Gy/fr on the elective sites and 55 Gy at 2.2 Gy/fr on the disease and mesorectum. Patients were divided in two groups based on whether they received a simultaneous integrated RT boost on the LPLN or not. Overall Survival (OS), Disease Free Survival (DFS), Metastasis Free Survival (MFS), and Local Control (LC) were evaluated in the whole group and then compared between the two groups. Results: A total of 176 patients were evaluated: 82 were included in the RT boost group and 94 in the non-RT boost group. The median follow-up period was 57.8 months. All the clinical endpoint (OS, DFS, MFS, LC), resulted were affected by the simultaneous integrated boost on LPLN with a survival rate of 84.7%, 79.5%, 84.1%, and 92%, respectively, in the entire population. From the comparison of the two groups, there was a statistical significance towards the RT boost group with a p < 0.006, 0.030, 0.042, 0.026, respectively. Conclusions: Concomitant radiotherapy boost on positive LPLN has shown to be beneficial on the survival outcomes (OS, DFS, MFR, and LC) in patients with LARC and LPLN. This analysis demonstrates that a higher dose of radiotherapy on positive pelvic lymph nodes led not only to a higher local control but also to a better survival rate. These results, if validated by future prospective studies, can bring a valid alternative to the surgery dissection without the important side effects and permanent disabilities observed during the years. Full article

Background: The balance between quality of life and colorectal cancer risk in familial adenomatous polyposis (FAP) patients is of primary importance. A cut-off of less than 30 polyps under 1 cm of diameter in the rectum has been used as an indication for performing ileo-rectal anastomosis (IRA) in terms of lower rectal cancer risk. This study aimed to assess clinical and surgical features of FAP patients who developed cancer of the rectal stump. Methods: This retrospective study included all FAP patients who underwent total colectomy/IRA from 1977 to 2021 and developed subsequent rectal cancer. Patients’ features were reported using descriptive statistics by considering the overall case series and within pre-specified classes of age (<20, 20–30, and >30 years) at first surgery. Results: Among the 715 FAP patients, 47 (6.57%, 95% confidence interval: 4.87; 8.65) developed cancer in the rectal stump during follow-up. In total, 57.45% of the population were male and 38.30% were proband. The median interval between surgery and the occurrence of rectal cancer was 13 years. This interval was wider in the youngest group (p-value: 0.012) than the oldest ones. Twelve patients (25.53%) received an endoscopic or minimally invasive resection. Amongst them, 61.70% were Dukes stage A cancers. Conclusions: There is a definite risk of rectal cancer after total colectomy/IRA; however, the time interval from the index procedure to cancer developing is long. Minimally invasive and endoscopic treatments should be the procedures of choice in patients with early stage cancers. Full article

More than 40% of patients with colorectal cancer present liver metastases (CRLM) during the course of their disease and up to 50% present with unresectable disease. Without surgical interventions, survival for patients treated with systemic therapies alone is dismal. In the past, liver transplantation (LT) for patients with unresectable CRLM failed to show any survival benefit due to poor selection, ineffective chemotherapeutic regimens, unbalanced immunosuppression and high perioperative mortality. Since then and for many years LT for CRLM was abandoned. The turning point occurred in 2013, when the results from the Secondary Cancer (SECA I) pilot study performed at Oslo University were published reporting a 60% 5-year overall survival after LT in patients with unresectable CRLM. These results effectively reignited the interest in LT as a potential therapy for CRLM, and several trials are undergoing. The aims of this article are to give a comprehensive overview of the available evidence on LT for CRLM, discuss the open issues in this rapidly evolving field, and highlight possible ways to address the future of this fascinating therapeutic alternative for selected patients with CRLM. Full article

Total neoadjuvant therapy (TNT)—the neoadjuvant employment of radiotherapy (RT) or chemoradiation (CRT) as well as chemotherapy (CHT) before surgery—may lead to increased pathological complete response (pCR) rates as well as a reduction in the risk of distant metastases in locally advanced rectal cancer. Furthermore, increased response rates may allow organ-sparing strategies in a growing number of patients with low rectal cancer and upfront immunotherapy has shown very promising early results in patients with microsatellite instability (MSI)-high/mismatch-repair-deficient (dMMR) tumors. Despite the lack of a generally accepted treatment standard, we strongly believe that existing data is sufficient to adopt the concept of TNT and immunotherapy in clinical practice. The treatment algorithm presented in the following is based on our interpretation of the current data and should serve as a practical guide for treating physicians—without any claim to general validity. Full article

It is important to understand advances in treatment options for rectal cancer. We attempt to highlight advances in rectal cancer treatment in the form of a systematic review. Early-stage rectal cancer focuses on minimally invasive endoluminal surgery, with importance placed on patient selection as the driving factor for improved outcomes. To achieve a complete pathologic response, various neoadjuvant chemoradiation regimens have been employed. Short-course radiation therapy, total neoadjuvant chemotherapy, and others provide unique advantages with select patient populations best suited for each. With a clinical complete response, a “watch and wait” non-operative surveillance has been introduced with preliminary equivalency to radical resection. Various modalities for total mesorectal excision, such as robotic or transanal, have advantages and can be utilized in select patient populations. Tumors demonstrating solid organ or peritoneal spread, traditionally defined as unresectable lesions conveying a terminal diagnosis, have recently undergone advances in hepatic and pulmonary metastasectomy. Hepatic and pulmonary metastasectomy has demonstrated clear advantages in 5-year survival over standard chemotherapy. With the peritoneal spread of colorectal cancer, HIPEC with cytoreductive therapy has emerged as the preferred treatment. Understanding the various therapeutic interventions will pave the way for improved patient outcomes. Full article

The surgical management of low-lying rectal cancer, within 5 cm from the anal verge (AV), is challenging due to the possibility, or not, to preserve the anus with its sphincter muscles maintaining oncological safety. The standardization of total mesorectal excision, the adoption of neoadjuvant chemoradiotherapy, the implementation of rectal magnetic resonance imaging, and the evolution of mechanical staplers have increased the rate of anus-preserving surgeries. Moreover, extensive anatomy and physiology studies have increased the understanding of the complexity of the deep pelvis. Intersphincteric resection (ISR) was introduced nearly three decades ago as the ultimate anus-preserving surgery. The definition and indication of ISR have changed over time. The adoption of the robotic platform provides excellent perioperative results with no differences in oncological outcomes. Pushing the boundaries of anus-preserving surgeries has risen doubts on oncological safety in order to preserve function. This review critically discusses the oncological safety of ISR by evaluating the anatomical characteristics of the deep pelvis, the clinical indications, the role of distal and circumferential resection margins, the role of the neoadjuvant chemoradiotherapy, the outcomes between surgical approaches (open, laparoscopic, and robotic), the comparison with abdominoperineal resection, the risk factors for oncological outcomes and local recurrence, the patterns of local recurrences after ISR, considerations on functional outcomes after ISR, and learning curve and surgical education on ISR. Full article

Recently, two large, randomised phase III clinical trials of total neoadjuvant therapy (TNT) in locally advanced rectal cancer were published (RAPIDO and PRODIGE 23). These two trials compared short-course radiotherapy (SCRT) followed by chemotherapy with standard chemoradiotherapy (CRT) and chemotherapy followed by CRT with standard CRT, respectively. They showed improvement in some of the outcomes such as distant recurrence and pathological complete response (pCR). No improvement, however, was observed in local disease control or the de-escalation of surgical procedures. Although it seems lawful to integrate TNT within the treatment algorithm of localised stage II and III rectal cancer, many questions remain unanswered, including which are the optimal criteria to identify patients who are most likely to benefit from this intensive treatment. Instead of providing a sterile summary of trial results, we put these in perspective in a pros and cons manner. Moreover, we discuss some biological aspects of rectal cancer, which may provide some insights into the current decision-making process, and represent the basis for the future development of alternative, more effective treatment strategies. Full article