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El manejo multimodal del cáncer de recto, localmente avanzado (LARC), se ha convertido en las últimas décadas en el estándar terapéutico de este tipo de tumores, logrando cifras de recidiva local global alrededor del 10%. Sin embargo, las tasas de sobrevida global (OS) y de sobrevida libre de enfermedad (DFS) no superan el 75% en la mayoría de las series, debido a las fallas a distancia. La investigación de nuevas terapias que logren un control efectivo de la enfermedad sistémica se ha focalizado en agregar a la radioterapia pélvica distintos esquemas de quimioterapia en la etapa preoperatoria, es decir, neoadyuvante. En esta revisión se discuten los distintos esquemas denominados genéricamente TNT (total neoadjuvant therapy), las ventajas y las limitaciones de este nuevo enfrentamiento del LARC, basado principalmente en los estudios prospectivos y aleatorizados disponibles a la fecha, con foco en los resultados en OS y DFS.
Neoadjuvant chemoradiation followed by surgery with or without adjuvant chemotherapy has remained the mainstay of treatment of locally advanced rectal cancer (LARC) for the past two decades. Although this regimen has reduced rates of local recurrence to 10% or less, rates of systemic failure are 20 to 30%, leading to a 5-year survival of 70-75%, at best. This situation has led to investigations into the use of total neoadjuvant therapy in the form of induction or consolidation chemotherapy. This review put the focus on final outcomes like overall survival and disease-free survival based on the available prospective and randomized studies about different schemes of TNT.
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Surgical resection is one of the main steps in the treatment of locally advanced rectal cancer. With the popularization of total mesorectal resection and laparoscopic minimally invasive techniques, related current research on surgical treatment has now entered a relatively high-level stage. In this article, we review the research frontiers of surgical treatment on rectal cancer, including reduction of trocars, specimen retrieval through natural orifices, robotic surgery, high definition/3D/indocyanine fluorescence green surgery, surgical approach and key surgery technology. Based on the current environment of evidence-based medicine, colorectal surgeons should adapt to the changes of the times, actively absorb cutting-edge scientific concepts and technologies and integrate them with surgical equipment and instruments, and carry out rigorous and innovative large-scale prospective clinical trials.
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The treatment of locally advanced rectal cancer (LARC) is extremely challenging, and it is difficult to achieve satisfactory results with surgical resection alone. In recent years, the diagnosis and treatment of LARC tends to be multi-disciplinary (MDT) mode. The emerging neoadjuvant treatment strategy is a milestone. At present, the preferred treatment for LARC is neoadjuvant chemoradiotherapy combined with total mesorectal excision. This article summarizes the main treatments of LARC neoadjuvant therapy, hoping to provide reference for clinical diagnosis and treatment.
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Objective:To investigate the clinical factors influencing the efficacy and prognosis of neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC).Methods:The clinical data of 335 patients with LARC who underwent radical operation after nCRT in Liaoning Cancer Hospital were retrospectively analyzed.Through univariate and multivariate analysis, we found out the clinical factors that may affect the efficacy and prognosis of nCRT in patients with LARC.Results:Multivariate logistic regression analysis showed that the independent clinical factors influencing the curative effect of nCRT in LARC patients were tumor invasion circumference( OR=2.350, 95% CI: 1.438-3.842, P=0.01), cT stage( OR=2.101, 95% CI: 1.024-4.314, P=0.043) and cN stage( OR=5.836, 95% CI: 3.305-10.306, P<0.01). Competitive risk model analysis showed that the independent factors affecting the prognosis of LARC patients were tumor regression grading (TRG) ( HR=3.236, 95% CI: 1.714-6.110, P<0.01), cT stage ( HR=1.852, 95% CI: 1.061-3.230, P=0.030), cN stage ( HR=2.008, 95% CI: 1.083-0.372, P=0.027), and carcinoembryonic antigen (CEA) level before nCRT ( HR=7.038, P<0.01), 95% CI: 3.894-12.720, P<0.01) and serum carbohydrate antigen 199 (CA199) ( HR=3.849, 95% CI: 2.016-7.350, P<0.01). Conclusion:The larger the circumference of tumor invasion before nCRT, cT stage and the cN stage were independent clinical factors influencing the nCRT efficacy of LARC patients.The larger the degree of tumor invasion to the rectum, the higher cT stage and the higher the cN stage before nCRT, the worse the efficacy of nCRT in LARC patients may be. TRG grade, cT stage, cN stage, CEA and CA199 level before nCRT were independent factors affecting the prognosis of LARC patients who received nCRT. The higher the TRG grade, of LARC patients receiving nCRT, the higher cT and cN stage, and the higher the CEA and CA199 level before nCRT, the worse the prognosis of LARC patients may be.
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Objective: To evaluated the prognostic effect of tumor volume in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (NCRT) and total mesorectal excision (TME). Methods: This was a retrospective analysis of 128 patients with newly diagnosed rectal cancer who received preoperative concurrent chemoradiation plus TME from January 2011 to September 2016 in Hunan Cancer Hospital. The receiver-operating characteristic (ROC) curve was used to analyze the gross tumor volume (GTV) cut-off point. Prognostic analysis was performed using Kaplan-Meier, Log-rank, and Cox regression models. Results: After NCRT, T-stage declined 58.6%, N-stage declined 69.5%, and the overall TNM stage declined 77.3%. After NCRT, the pathological complete response (pCR) rate was 16.4% and the anus-protection rate was 57.03%. The GTV cut-off point was 79.31 mL. There were significant differences in OS, DFS, LRFS and DMFS between patients with GTV ≥79.31 mL and patients with GTV <79.31 mL over three years. GTV was significantly related to MRI-T staging (ρ=0.236; P=0.007), T downstaging (ρ=0.229; P=0.009),TNM downstaging (ρ=0.219; P=0.013), and tumor regression grade (TRG) (ρ=0.517; P<0.001); however, GTV was not significantly related to MRI-N staging and N downstaging. Conclusions: GTV is closely related to local recurrence and distant metastasis of LARC, and is an important prognostic factor. Tumor volume was significantly related to pretreatment MRI-T staging, T downstaging, TNM downstaging after NCRT, and TRG, but not to pretreatment MRI-N staging and N downstaging.
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Objective Only 10%-30% of locally advanced rectal cancer (LARC) respond pathologically to neoadjuvant chemoradiotherapy (NCRT). This study was to search for a feasible gene signature predicting pathological response to NCRT in LARC. Methods Four datasets GSE35452, GSE46862, GSE68204 and GSE53781 relating to the mRNA expression matrix and tumor regression grading of LARC after NCRT were obtained from the Gene Expression Omnibus. The first three datasets were merged into one and divided into training sets (n = 121) and internal validation sets (n = 53) after batch effect removal, and the last dataset was used as external validation sets (n = 26). Pathological response-related genes in the training sets were identified by univariate logistic regression and t-test (crude P < 0.05) and ranked by the P-value. All the genes with P < 0.05 were subjected to the least absolute shrinkage and selection operator (LASSO) and the first 50 to the support vector machine algorithm (SVM) for the establishment of predicting models, followed by verification in the corresponding validation set. Random sampling was repeated 500 times to determine the stability of the selected gene signatures and models. With the 21 most important genes revealed by LASSO as the candidates for model construction, the sensitivity index for NCRT was calculated as the total sum of coefficients in logistic regression and expression values in the merged datasets and external validation sets. The differentially expressed genes were identified between the response and non-response groups in the 174 merged datasets and subjected to regulatory network analysis. Results A total of 12 803 genes from the GSE35452, GSE46862 and GSE68204 datasets were included in the analysis. The accuracy, specificity and sensitivity of LASSO for predicting the pathological response in the internal validation sets were 0.523 (95% CI: 0.396-0.642, 0.578 (95% CI: 0.373-0.762) and 0.464 (95% CI: 0.258-0.700), while those of SVM were 0.504 (95% CI: 0.377-0.623), 0.596 (95% CI: 0.393-0.830) and 0.405(95% CI: 0.182-0.650), respectively. The area under the ROC curve (AUC) for pathological response prediction was 0.863 (95% CI: 0.811-0.912) in the 174 merged datasets and 0.925 (95% CI: 0.817-1.000) in the external validation sets. Conclusion The model for predicting response to NCRT established using the expression of candidate genes identified from a specific set of patients has a frustratingly low capacity in an independent set, probably because of high tumor heterogeneity among different individuals. Regulatory network analysis indicates that radiotherapy-resistance in rectal cancer may be mediated by the mechanisms underlying the invasion, metastasis and transformation of the malignancy.
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Objective To investigate the application value of diameter change of superior rectal vein (SRV) and inferior mesenteric vein (IMV) by CT examination in the efficacy evaluation of neoadjuvant therapy for locally advanced rectal cancer.Methods The retrospective descriptive study was conducted.The clinicopathological data of 40 patients with locally advanced rectal carcer who underwent neoadjuvant therapy in the First Affiliated Hospital of Chongqing Medical University were collected.There were 28 males and 12 females,aged from 12 to 75 years,with the age of (55± 12)years.All patients underwent radical resection of rectal cancer according to the principle of total mesorectal resection after neoadjuvant therapy.Observation indicators:(1) MRI examination;(2) CT examination;(3) surgical situations;(4) follow-up.Follow-up was performed using outpatient examination to detect postoperative complications up to June 2019.The measurement data with normal distribution were represented as Mean±SD,and paired sample t test was used for intra-group comparison.Count data were described as absolute numbers or percentages.Results (1) MRI examination:there were 22 patients with positive extramural vascular invasion (EMVI) and 18 with negative EMVI.(2) CT examination:the diameter of SRV was (3.9 ± 0.9) mm and (3.0 ± 0.6) mm before and after neoadjuvant therapy,showing a significant difference (t=5.75,P＜0.05).Subgroup analysis:for the 30 patients with response to neoadjuvant therapy,the diameter of SRV changed significantly after neoadjuvant therapy [(4.1 ± 1.0) mm vs.(3.4±0.7) mm,t =6.20,P＜0.05];for the 10 patients without response to neoadjuvant therapy,the diameter of SRV showed no significant difference after neoadjuvant treatment [(3.6±0.6)mm vs.(3.5±0.8)mm,t=1.13,P＞0.05].The diameter of SRV was (4.2±0.8)mm in 22 patients with EMVI and (3.7±0.8)mm in 18 patients with negative EMVI,showing a significant difference between the two groups (t =2.45,P＜0.05).The diameter of IMV was (5.1 ± 0.9)mm and (4.2±0.9)mm before and after neoadjuvant therapy,showing a significant difference (t=4.16,P＜ 0.05).Subgroup analysis:for the 30 patients with response to neoadjuvant therapy,the diameter of IMV changed significantly after neoadjuvant treatment [(5.1 ± 0.9) mm vs (4.6± 0.8) mm,t =0.76,P＜ 0.05];for the 10 patients without response to neoadjuvant therapy,the diameter of SRV showed no significant difference after neoadjuvant treatment [(5.0±0.9)mm vs (4.8±1.0)mm,t=0.76,P＞0.05].The diameter of IMV was (4.8± 0.9) mm in 22 patients with EMVI and (4.6±0.8) mm in 18 patients with negative EMVI,showing no significant difference between the two groups (t =2.45,P＞ 0.05).(3) Surgical situations:40 patients underwent radical resection of rectal cancer,including 4 with synchronous liver metastases undergoing resection of metastases.(4) Follow-up:40 patients were followed up for 3.0-6.0 months,with a median follow-up time of 4.5 months.One of 40 patients with perineal incision infection was improved and discharged after dressing change,1 with anastomotic leakage on the 5th day after operation was improved and discharged after conservative treatment,1 of 2 with adhesive intestinal obstruction was improved after surgery and 1 was improved after conservative treatment,other 36 patients were discharged and no obvious abnormality occured during the follow-up.Conclusions The diameters of SRV and IMV in patients with locally advanced rectal cancer can be significantly decreased significantly after neoadjuvant therapy.The diameters of SRV and IMV can be used as potential indices to evaluate the effects of neoadjuvant therapy for rectal cancer,and the SRV had a higher evaluation value.
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Objective To investigate the effect of Avastin (bevacizumab) combined with preoperative FOLFOX neoadjuvant chemotherapy on the prognosis of patients with locally advanced rectal cancer (LARC).MethodsA total of 80 cases of patients with LARC treated with total mesorectal excision (TME) in our hospital from January 2013 to January 2016 were randomly divided into the control group and the observation group, 40 cases in each group.The control group were treated with preoperative FOLFOX chemotherapy while the observation group were treated with bevacizumab injection, based on the treatment in the control group.21 days was a cycle of chemotherapy, and both groups were treated for at least 4 cycles.After 6 cycles of chemotherapy, operation was carried out, following TEM principle.The short-term and long-term prognosis, rate of R0 resection, the incidence of postoperative complications and side effects of chemotherapy were compared between the two groups.ResultsThere was no significant difference between the two groups in the good response rate of chemotherapy, the rate of R0 resection, the incidence of postoperative complications, the 1-year and 3-year survival rates and 1-year disease-free survival rate.The incidence rates of gastrointestinal reactions and bone marrow suppression in the observation group were 52.5% and 52.5%, respectively while in the control group were 25.0% and 20.0%, respectively (P<0.05), but there was no significant difference in the incidence rates of grade Ⅲ~Ⅳ gastrointestinal reaction and bone marrow suppression between the observation group and the control group (5.0% and 15.0% vs 2.5% and 5.0%).The 3-year disease-free survival rate of the observation group was higher than that of the control group (82.5% vs 60.0%) (P<0.05).ConclusionThe application of bevacizumab combined with preoperative FOLFOX chemotherapy in the treatment of LARC can improve the 3-year disease-free survival rate, without increasing postoperative adverse reactions and serious side effects of chemotherapy.
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Objective To evaluate the efficacy and safety of adding neoadjuvant chemotherapy following neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer.Methods A total of 80 patients confirmed with locally advanced rectal cancer were enrolled during January 2012 and December 2015 in Guizhou Medical University Affiliated Cancer Hospital and were randomized with the method of lottery into the experimental group and the control group.In the experimental group,40 patients received 4 cycles of FOLFOX4 after chemoradiotherapy and then had total mesorectal excision (TME).Another 4 cycles of FOLFOX4 were administered after surgery.In the control group,40 patients had TME surgery 6-8 weeks after chemoradiotherapy and received 8 cycles of FOLFOX4 as adjuvant chemotherapy.Pelvic radiotherapy dose was 50 Gy in 25 fractions,5 days per week for 5 weeks.5-Fu continuous infusion was administered throughout radiotherapy.The pCR rate,downstaging rate,R0 resection rate,local recurrence rate,distant metastasis rate,survival rate,incidence of toxicities,surgical complications and completion of treatment were observed.Results The pCR rate was 20.0％ in the experimental group and 5.0％ in the control group (x2 =4.114,P ＜ 0.05).The downstaging rate was 77.4％ in the experimental group and 55.6％ in the control group(P ＞ 0.05).No statistically significant difference was observed in R0 resection rate,3-year local recurrence rate,3-year distant metastasis rate and 3-year survival rate between the two groups (P ＞ 0.05).Patients in the experimental group had higher completion rate of 8 cycles of systemic chemotherapy (87.1％ vs.61.5％,x2 =4.985,P ＜0.05).No statistically significant difference was observed in acute toxicities and postoperative complications.Conclusions Adding systemic chemotherapy after neoadjuvant chemoradiotherapy for locally advanced rectal cancer has significantly higher pCR rate and lower toxicities and side events compared with chemoradiotherapy alone.Longer follow-up and larger scale of clinical research are needed.Trial registration Chinese clinical trial registry,ChiCTR-IPR-17010454.
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PURPOSE: Locally advanced rectal cancer may require an intraoperative decision regarding curative multivisceral resection (MVR) of adjacent organs. In bulky tumor cases, ensuring sufficient distal resection margin (DRM) for achievement of oncologic safety is very difficult. This study is designed to evaluate the adequate length of DRM in multiviscerally resected rectal cancer. METHODS: A total of 324 patients who underwent curative low anterior resection for primary pT3-4 rectal cancer between 1995 and 2004 were identified from a prospectively collected colorectal database. RESULTS: Short lengths of DRM ( or =2 cm) showed 72.4% and 60.2% (P = 0.03, 0.044). In multivariate analysis of MVR, poorly differentiated histology, ulceroinfiltrative growth of tumor, and short DRM (<2 cm) were significant factors for prediction of poor survival outcome, although short DRM was not significantly related to local and systemic recurrence. CONCLUSION: In locally advanced rectal cancer of pT3-4, a short length of DRM (< or =1 cm) did not compromise essentially poor oncologic outcome. In rectal cancers invading adjacent organs and requiring MVR, a shorter DRM (<2 cm) was found to be related to poor survival outcome.
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Humans , Achievement , Multivariate Analysis , Prospective Studies , Rectal NeoplasmsABSTRACT
Objective: To evaluate the influence of preoperative chemoradiation in locally advanced rectal cancer on ability to perform sphincter preserving surgery. Methods: Between 1998 and 2005, a prospective clinical trial of preoperative chemoradiation therapy (CTX/XRT) that delivered 45 Gy in 25 fractions over 5 weeks with bolus infusion of 5-fluorouracil (200 mg/m2/day) or capecitabine (2000mg/m2/day) was given to 42 rectal cancer patients admitted to the Department of Surgery, Siriraj Hospital, Bangkok, Thailand. The pretreatment stage distribution, as determined by endorectal ultrasonography and computed tomography of the pelvis, included uT3N0 in 90.48% and uT3N1 in 9.52% of cases. Approximately 6 weeks after completion of CTX/XRT, surgery was performed in every patient. The choice of the surgical procedure was based on the surgeon’s discretion. Results: The patient population consisted of 25 males (59.52%) and 17 females (40.48%) who had a median age of 57 years (range 32-79 years). Distal border of the tumors were located at a median of 5 cm (range 2-10 cm) above the anal verge. Thirty cases (71.43%) had distal border of the tumors within 6 cm from the anal verge. The pathological tumor stages were T1N0 in 2 cases (4.76%), T2N0 in 9 cases (21.43%), T2N1 in 4 cases (9.52%), T3N0 in 12 cases (28.57%), T3N1 in 8 cases (19.05%), T3N2 in 2 cases (4.76%) and T4N0 in 1 case (2.38%). The results included 9.52% pathological complete response, 42.86% downstaging and 50% sphincter preservation rate. Of the tumors located < 6 cm from the anal verge, sphincter preservation was accomplished in 30% of the patients. The pretreatment location of distal border of the tumors (< 6 cm vs. > 6 cm from anal verge) was the only factor predictive of sphincter preservation (p < 0.001). No local recurrence was detected during the period of follow up (median 23 months). Conclusion: The administration of preoperative chemoradiation for locally advanced rectal cancer is associated with tolerable toxicity and high rates of tumor downstaging. The preoperative chemoradiation and tumor downstaging do not increase rate of sphincter preservation in locally advanced rectal cancer.
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PURPOSE: The purpose of this study is to evaluate the value of pelvic exenteration (PE) for recurrent or locally advanced rectal cancer. METHODS: This retrospective study analyzed 20 patients who underwent PE for rectal cancer from June 1994 to October 2003 in Ajou University Hospital. The surgical severity, the postoperative complications, and the survival rate were analyed based on the medical records. RESULTS: The mean operation time was 221.5+/-93.0 minutes, the mean blood loss 750.5+/-223.3 cc, and the mean transfusion amount RBC 6.5+/-4.3 units. Operative mortality was 5% (1/20). A bleeding-associated complication was noted in one patient who underwent a reoperation for hemostasis. Other minor complications were small bowel obstruction (n=3), abdominal wound infection (n=5), vesicocutaneous fistula (n=2), delayed healing of the perineal wound (n=10). The overall 5-year survival rate was 52.6% (10 of 19 patients, excluding the operative mortality case). CONCLUSIONS: Our study showed acceptable surgical severity and postoperative complications and a favorable 5-year survival rate (> or =50%) for pelvic exenteration as a treatment for recurrent or locally advanced rectal cancer. With strictly selected patients, PE may be one of the treatment options for recurrent or locally advanced rectal cancer.