How appropriate is treating patients diagnosed with advanced esophageal cancer with anticancer drugs? A multicenter retrospective cohort Spanish study.

AIM: To assess the appropriateness of systemic oncological treatments (SOT) provided to patients diagnosed with advanced esophageal cancer (EC) across a group of participating hospitals. METHODS: Multicenter, retrospective cohort study in five Spanish hospitals including newly confirmed advanced EC cases between July 1, 2014, and June 30, 2016, with a 5-year follow-up. RESULTS: We identified 157 patients fulfilling the inclusion criteria (median age: 65 years, 85.9% males). Most patients, 125 (79.6%) were treated at least with one active treatment, and 33% received two or more lines of SOT. The 1-, 2- and 5-year overall survival rates were 30.3% [95%CI: 23.8, 38.7], 14.0% [95%CI: 9.3, 21.0], and 7.1% [95% CI: 3.8, 13.1] respectively, and the median survival time 8 months (95% CI: 6, 19) for stages IIIb IIIc and 7 months (95% CI: 5, 9) for stage IV. Clinical stage, receiving more than one line of SOT, and treatment with radiotherapy accelerated the time to death (0.4, 0.9-, and 0.8-times shorter survival respectively, p < 0.05). Better performance status (ECOG < 2) extended survival time by 2.2 times (p = 0.04). Age < 65 years (OR 9.4, 95% CI 3.2, 31.4, p < 0.001), and being treated in one particular hospital (OR 0.2, 95% CI 0.0, 0.8, p < 0.01) were associated with the administration of two or more lines of SOT. Altogether, 18.9% and 9.0% of patients received chemotherapy in the last four and two weeks of life, respectively. Moreover, 2.5% of patients were prescribed a new line of chemotherapy during the last month of life. The proportion of all patients who did not have access to palliative care reached 29.3%, and among those who had access to it, 34.2% initiated it in the last month of life. CONCLUSION: A high proportion of advanced EC patients receive many treatments not based on sound evidence and they do not benefit enough from palliative care services. The most accepted appropriateness indicators point out that some of the analyzed patients could have been overtreated. This study provides important insights into the quality of care provided to advanced EC, and furthermore, for giving valuable insight and opportunities for improvement.

Nab-Paclitaxel plus Gemcitabine and FOLFOX in Metastatic Pancreatic Cancer.

Nab-Paclitaxel plus Gemcitabine and FOLFOXThis randomized, open-label, phase II trial compared nab-paclitaxel/gemcitabine followed by modified FOLFOX versus nab-paclitaxel/gemcitabine alone for the first-line treatment of metastatic pancreatic ductal adenocarcinoma. Patients receiving nab-paclitaxel plus gemcitabine followed by modified FOLFOX-6 (oxaliplatin, leucovorin, and 5-fluorouracil) had a 12-month and 24-month overall survival of 55.3% and 22.4%, respectively, compared with 35.4% and 7.6% in the control group; there was a higher incidence of grade 3 or higher neutropenia and thrombocytopenia. No significant differences in febrile neutropenia, epistaxis or hemorrhage of grade 3 or higher in either group were reported. Two toxic deaths (2.6%) occurred in the experimental group.

Real-World Outcomes in Patients with Metastatic Colorectal Cancer in Spain: The RWD-ACROSS Study.

The retrospective, observational RWD-ACROSS study analyzed disease characteristics, systemic treatment, and survival in patients with metastatic colorectal cancer (mCRC) in Spain. In total, 2002 patients were enrolled (mean age 65.3 years; 62.7% male). Overall median overall survival (OS) was 26.72 months, and was longer in patients with left-sided tumors (28.85 vs. 21.04 months (right-sided tumors); p < 0.0001) and in patients receiving first-line anti-epidermal growth factor receptor (EGFR) treatment (31.21 vs. 26.75 (anti-vascular endothelial growth factor (VEGF) treatment) and 24.45 months (chemotherapy); p = 0.002). Overall median progression-free survival (PFS) was 10.72 months and was longer in patients with left-sided tumors (11.24 vs. 9.31 months (right-sided tumors); p < 0.0001), and in patients receiving either first-line anti-EGFR or anti-VEGF (12.13 and 12.00 vs. 8.98 months (chemotherapy); p < 0.001). PFS was longer with anti-VEGF treatment in patients with right-sided tumors and wild-type RAS (11.24 vs. 8.78 (anti-EGFR) and 7.83 months (chemotherapy); p = 0.025). Both anti-EGFR and anti-VEGF produced longer PFS in patients with left-sided tumors and wild-type RAS than chemotherapy alone (12.39 and 13.14 vs. 9.83 months; p = 0.011). In patients with left-sided tumors and mutant RAS, anti-VEGF produced a longer PFS than chemotherapy alone (12.36 vs. 9.34 months; p = 0.001). In Spain, wild-type RAS or left-sided mCRC tumors are predictive of longer survival times.

Treatment with anticancer drugs for advanced pancreatic cancer: a systematic review.

BACKGROUND: Patients with advanced pancreatic cancer have a poor prognosis and high burden of cancer-related symptoms. It is necessary to assess the trade-off of clinical benefits and possible harms of treatments with anticancer drugs (TAD). This systematic review aims to compare the effectiveness of TAD versus supportive care or no treatment, considering all patient-important outcomes. METHODS: We searched PubMed, Embase, Cochrane Library, and Epistemonikos. Two reviewers performed selection, data extraction and risk of bias assessment. We assessed certainty of the evidence using the GRADE approach. RESULTS: We included 14 randomised controlled trials. Chemotherapy may result in a slight increase in overall survival (MD: 2.97 months (95%CI 1.23, 4.70)) and fewer hospital days (MD: -6.7 (-8.3, -5.1)), however, the evidence is very uncertain about its effect on symptoms, quality of life, functional status, and adverse events. Targeted/biological therapy may result in little to no difference in overall survival and a slight increment in progression-free survival (HR: 0.83 (95%CI 0.63, 1.10)), but probably results in more adverse events (RR: 5.54 (95%CI 1.24, 23.97)). The evidence is very uncertain about the effect of immunotherapy in overall survival and functional status. CONCLUSIONS: The evidence is very uncertain about whether the benefits of using treatment with anticancer drugs outweigh their risks for patients with advanced pancreatic cancer. This uncertainty is further highlighted when considering immunotherapy or a second line of chemotherapy and thus, best supportive care would be an appropriate alternative. Future studies should assess their impact on all patient-important outcomes to inform patients in setting their goals of care.

Real-world study on microsatellite instability and mismatch repair deficiency testing patterns among patients with metastatic colorectal cancer in Spain.

PURPOSE: Clinical practice guidelines recommend that all patients with metastatic colorectal cancer (mCRC) should be tested for mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H). We aimed to describe the dMMR/MSI-H testing practice in patients with mCRC in Spanish centers. METHODS: Multicenter, observational retrospective study that included patients newly diagnosed with mCRC or who progressed to a metastatic stage from early/localized stages. RESULTS: Three hundred patients were included in the study from May 2020 through May 2021, with a median age of 68 years, and two hundred twenty-five (75%) had stage IV disease at initial diagnosis; two hundred eighty-four patients received first-line treatment, and dMMR/MSI-H testing was performed in two hundred fifty-one (84%) patients. The results of the dMMR/MSI-H tests were available in 61 (24%) of 251 patients before the diagnosis of metastatic disease and in 191 (81%) of 236 evaluable patients for this outcome before the initiation of first-line treatment. Among the 244 patients who were tested for dMMR/MSI-H with IHC or PCR, 14 (6%) were MMR deficient. The most frequent type of first-line treatment was the combination of chemotherapy and biological agent, that was received by 71% and 50% of patients with MMR proficient and deficient tumors, respectively, followed by chemotherapy alone, received in over 20% of patients in each subgroup. Only 29% of dMMR/MSI-H tumors received first-line immunotherapy. CONCLUSION: Our study suggests that a high proportion of patients with mCRC are currently tested for dMMR/MSI-H in tertiary hospitals across Spain. However, there is still room for improvement until universal testing is achieved. TRIAL REGISTRATION: Not applicable.

Total neoadjuvant therapy with or without aflibercept in rectal cancer: 3-year results of GEMCAD-1402.

BACKGROUND: The results of the Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD)-1402 phase II randomized trial suggested that adding aflibercept to modified fluorouracil, oxaliplatin, and leucovorin (mFOLFOX6) induction, followed by chemoradiation and surgery, could increase the pathological complete response (pCR) rate in patients with high-risk, locally advanced rectal cancer. Here we update results up to 3 years of follow-up and evaluate the predictive value of consensus molecular subtypes identified with immunohistochemistry (IHC). METHODS: Patients with magnetic resonance imaging-defined T3c-d and/or T4 and/or N2 rectal adenocarcinoma in the middle or distal third were randomly assigned to mFOLFOX6 induction, with aflibercept (mF+A; n = 115) or without aflibercept (mF; n = 65), followed by capecitabine plus radiotherapy and surgery. The risk local relapse, distant metastases, disease-free survival (DFS), and overall survival (OS) were estimated at 3 years. Selected samples were classified via IHC into immune-infiltrate, epithelial, or mesenchymal subtypes. RESULTS: mF+A and mF had 3-year DFS of 75.2% (95% confidence interval [CI] = 66.1% to 82.2%) and 81.5% (95% CI = 69.8% to 89.1%), respectively; 3-year OS of 89.3% (95% CI = 82.0% to 93.8%) and 90.7% (95% CI = 80.6% to 95.7%), respectively; 3-year cumulative local relapse incidences of 5.2% (95% CI = 1.9% to 11.0%) and 6.1% (95% CI = 1.7% to 15.0%), respectively; and 3-year cumulative distant metastases rates of 17.3% (95% CI = 10.9% to 25.5%) and 16.9% (95% CI = 8.7% to 28.2%), respectively. pCRs were achieved in 27.5% (n = 22 of 80) and 0% (n = 0 of 10) of patients with epithelial and mesenchymal subtypes, respectively. CONCLUSION: Adding aflibercept to mFOLFOX6 induction was not associated with improved DFS or OS. Our findings suggested that consensus molecular subtypes identified with IHC subtypes could be predictive of pCR with this treatment.

The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer.

BACKGROUND: Patients with metastatic colorectal cancer (mCRC) and KRAS mutations have a poor prognosis, seemingly dependent on the location of the mutation. This multicenter, retrospective, cohort study assessed the frequency and prognostic value of specific KRAS mutation codon locations in mCRC patients, and survival outcomes in relation to treatment. MATERIALS AND METHODS: Data from mCRC patients treated in 10 Spanish hospitals between January 2011 and December 2015 were analyzed. The main objective was to investigate (1) the impact of KRAS mutation location on overall survival (OS), and (2) the effect of targeted treatment plus metastasectomy and primary tumor location on OS in patients with KRAS mutations. RESULTS: The KRAS mutation location was known for 337/2002 patients. Of these, 177 patients received chemotherapy only, 155 received bevacizumab plus chemotherapy, and 5 received anti-epidermal growth factor receptor therapy plus chemotherapy; 94 patients underwent surgery. The most frequent KRAS mutation locations were G12A (33.8%), G12D (21.4%), and G12V (21.4%). Compared with other locations, patients with a G12S mutation had the shortest median OS (10.3 [95% CI, 2.5-18.0] months). OS was longer in patients who underwent surgery versus those who did not, with a trend toward prolonged survival with bevacizumab (median OS 26.7 [95% CI, 21.8-31.7] months) versus chemotherapy alone (median OS 23.2 [95% CI, 19.4-27.0] months). CONCLUSION: These findings confirm that KRAS mutation location may predict survival outcomes in patients with mCRC, and suggest that pre-/post-operative bevacizumab plus metastasectomy provides survival benefits in patients with KRAS mutations.

Teleoncology: A Solution for Everyone? A Single-Center Experience with Telemedicine during the Coronavirus Disease 2019 (COVID-19) Pandemic.

Since the beginning of the COVID-19 pandemic, the use of telehealth was rapidly implemented without previous evidence. The ONCOTELEMD study aimed to evaluate the opinion of patients attended via telemedicine during this period and to study factors that condition patient preferences on its use. Included patients had a confirmed cancer diagnosis and were contacted by telephone between 13 March and 30 April 2020, in the Medical Oncology Service of Hospital Parc Taulí, Sabadell. A 12-question survey was presented to them between 4 February and 19 April 2021. Statistical analysis was carried out using chi-square and multivariable logistic regression tests. Six hundred forty-six patients were included; 487 responded to the survey. The median age was 68 years (27-90), 55.2% were female. Most patients had a surveillance visit (65.3%) and were diagnosed with colorectal or breast cancer (43% and 26.5%, respectively); 91.8% of patients were satisfied, and 60% would accept the use of telemedicine beyond the pandemic. Patients aged more than 50 years (OR 0.40; 95% CI, 0.19-0.81; p = 0.01) and diagnosed with breast cancer (OR 0.45; 95% CI, 0.26-0.69; p < 0.001) were less predisposed to adopt telehealth in the future. Patients agreed to be informed via telehealth of scan or lab results (62% and 84%, respectively) but not of new oral or endovenous treatments (52% and 33.5%, respectively). Additionally, 75% of patients had a medium or low-null technologic ability, and 51.3% would only use the telephone or video call to contact health professionals. However, differences were found according to age groups (p < 0.0001). In total, patients surveyed were satisfied with telemedicine and believed telehealth could have a role following the COVID-19 pandemic. Moreover, our results remark on the importance of individualizing the use of telehealth, showing relevant data on patient preferences and digital literacy.

Patient experience, satisfaction and shared decision-making in colorectal cancer screening: protocol of the mixed-methods study CyDESA.

INTRODUCTION: Colorectal cancer (CRC) screening programmes can reduce incidence and mortality from this condition if adherence to them is high. As patient experience and satisfaction are key factors in determining adherence to screening programmes, they need to be measured. Furthermore, to promote highly patient-centred healthcare, the perception of patients regarding shared decision-making during CRC screening needs to be known. This study aims to assess the experience, satisfaction and participation in decision-making of participants in a CRC screening programme and of patients diagnosed with CRC through this programme in relation to the diagnostic and therapeutic processes of cancer. METHODS AND ANALYSIS: The CyDESA study is a mixed-methods study with a four phase sequential design. In phase 1, we will conduct a systematic review of patient-reported experience measures (PREMs) for patient experience or satisfaction with CRC screening. In case no located PREM can be applied, in phase 2, we will develop a new PREM. We will use the Delphi methodology to reach consensus among experts and patients and will conduct a pilot test of the developed PREM. Phase 3 is a multicentric cross-sectional study based on self-reported questionnaires that will be conducted at three Spanish hospitals (n=843). The objective is to find out about the experience, satisfaction and participation in decision-making of participants in the CRC screening programme who have had a positive screening test result according to their final screening diagnosis: false positives, colorectal polyps or CRC. Phase 4 is a qualitative phenomenological study based on individual interviews. It will explore the experiences of participants in the CRC screening programme and of those diagnosed with CRC. ETHICS AND DISSEMINATION: Ethics approval by the Ethics Committees of Corporació Sanitària Parc Taulí, Hospital de Sant Pau and Parc de Salut Mar. Findings will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: NCT04610086.

SEOM-GEMCAD-TTD clinical guidelines for localized rectal cancer (2021)

The management of localized rectal cancer requires a multidisciplinary approach to optimize outcomes, reduce morbidity and prevent under or overtreatments. While early stages may obtain benefit of local resections without any additional therapies, locally advanced rectal cancer becomes a challenge defining the better sequential strategy of surgery, radiotherapy and chemotherapy. The latest results of international phase III studies have positioned the total neoadjuvant therapy as a potential new standard of care in high risk rectal cancers, however, the best schedule is still not well defined.

SEOM-GEMCAD-TTD clinical guidelines for localized rectal cancer (2021).

The management of localized rectal cancer requires a multidisciplinary approach to optimize outcomes, reduce morbidity and prevent under or overtreatments. While early stages may obtain benefit of local resections without any additional therapies, locally advanced rectal cancer becomes a challenge defining the better sequential strategy of surgery, radiotherapy and chemotherapy. The latest results of international phase III studies have positioned the total neoadjuvant therapy as a potential new standard of care in high risk rectal cancers, however, the best schedule is still not well defined.

Efficacy and safety of trifluridine/tipiracil in older and younger patients with metastatic gastric or gastroesophageal junction cancer: subgroup analysis of a randomized phase 3 study (TAGS).

BACKGROUND: Trifluridine and tipiracil (FTD/TPI) demonstrated survival benefit vs placebo and manageable safety in previously treated patients with metastatic gastric/gastroesophageal junction cancer (mGC/GEJC) in the randomized, placebo-controlled, phase 3 TAGS study. This subgroup analysis of TAGS examined efficacy/safety outcomes by age. METHODS: In TAGS, patients with mGC/GEJC and ≥ 2 prior therapies were randomized (2:1) to receive FTD/TPI 35 mg/m2 or placebo, plus best supportive care. A preplanned subgroup analysis was performed to evaluate efficacy and safety outcomes in patients aged < 65, ≥ 65, and ≥ 75 years. RESULTS: Among 507 randomized patients (n = 337 FTD/TPI; n = 170 placebo), 55%, 45%, and 14% were aged < 65, ≥ 65, and ≥ 75 years, respectively. Overall survival hazard ratios for FTD/TPI vs placebo were 0.67 (95% CI 0.51-0.89), 0.73 (95% CI 0.52-1.02), and 0.67 (95% CI 0.33-1.37) in patients aged < 65, ≥ 65, and ≥ 75 years, respectively. Regardless of age, patients receiving FTD/TPI experienced improved progression-free survival and stayed longer on treatment than those receiving placebo. Among FTD/TPI-treated patients, frequencies of any-cause grade ≥ 3 adverse events (AEs) were similar across age subgroups (80% each), although grade ≥ 3 neutropenia was more frequent in older patients [40% (≥ 65 and ≥ 75 years); 29% (< 65 years)]; AE-related discontinuation rates did not increase with age [14% (< 65 years), 12% (≥ 65 years), and 12% (≥ 75 years)]. CONCLUSIONS: The results of this subgroup analysis show the efficacy and tolerability of FTD/TPI treatment regardless of age in patients with mGC/GEJC who had received 2 or more prior treatments.

Early Clinical Experience with Trifluridine/Tipiracil for Refractory Metastatic Colorectal Cancer: The ROS Study.

Trifluridine/tipiracil is currently approved for metastatic colorectal cancer (mCRC) refractory to available therapies. However, there is no consensus on factors that predict treatment outcomes in daily practice. We assessed the early clinical experience with trifluridine/tipiracil in Spain and potential survival markers. This was a retrospective cohort study of mCRC patients who participated in the trifluridine/tipiracil early clinical experience programme in Spain. The primary outcome was overall survival (OS). Associations between OS and patient characteristics were assessed using multivariate Cox regression analyses. A total of 379 patients were included in the study. Trifluridine/tipiracil was administered for a median of 3.0 cycles and discontinued mainly due to disease progression (79.2%). The median OS was 7.9 months, with a 12-month OS rate of 30.5%. Cox analyses revealed that the following variables independently enhanced OS: ≤2 metastatic sites, no liver metastasis, alkaline phosphatase < 300 IU, trifluridine/tipiracil dose reductions, and neutrophil/lymphocyte ratio < 5. Grade ≥ 3 toxicities were reported in 141 (37.2%) patients, including mainly afebrile neutropaenia (23.2%), anaemia (12.1%), and thrombocytopaenia (5.3%). This study supports the real-life efficacy and safety of trifluridine/tipiracil for refractory mCRC and identifies tumour burden, liver metastasis, alkaline phosphatase, dose reductions, and neutrophil/lymphocyte ratio as survival markers.

Preoperative Diagnostic Uncertainty in T2-T3 Rectal Adenomas and T1-T2 Adenocarcinomas and a Therapeutic Dilemma: Transanal Endoscopic Surgery, or Total Mesorectal Excision?

BACKGROUND: Endorectal ultrasound and rectal magnetic resonance are sometimes unable to differentiate between stages T2 and T3 in rectal adenomas that are possible adenocarcinomas, or between stages T1 and T2 in rectal adenocarcinomas. These cases of diagnostic uncertainty raise a therapeutic dilemma: transanal endoscopic surgery (TES) or total mesorectal excision (TME)? METHODS: An observational study of a cohort of 803 patients who underwent TES from 2004 to 2021. Patients operated on for adenoma (group I) and low-grade T1 adenocarcinoma (group II) were included. The variables related to uncertain diagnosis, and to the definitive pathological diagnosis of adenocarcinoma stage higher than T1, were analyzed. RESULTS: A total of 638 patients were included. Group I comprised 529 patients, 113 (21.4%) with uncertain diagnosis. Seventeen (15%) eventually had a pathological diagnosis of adenocarcinoma higher than T1. However, the variable diagnostic uncertainty was a risk factor for adenocarcinoma above T1 (OR 2.3, 95% CI 1.1-4.7). Group II included 109 patients, eight with uncertain diagnosis (7.3%). Two patients presented a definitive pathological diagnosis of adenocarcinoma above T1. CONCLUSIONS: On the strength of these data, we recommend TES as the initial indication in cases of diagnostic uncertainty. Multicenter studies with larger samples for both groups should now be performed to further assess this strategy of initiating treatment with TES.

Clinical Impact of Presurgery Circulating Tumor DNA after Total Neoadjuvant Treatment in Locally Advanced Rectal Cancer: A Biomarker Study from the GEMCAD 1402 Trial.

PURPOSE: Total neoadjuvant treatment (TNT) is a valid strategy for patients with high-risk locally advanced rectal cancer (LARC). Biomarkers of response to TNT are an unmet clinical need. We aimed to determine the value of circulating tumor DNA (ctDNA) to predict tumor response, recurrence, and survival in patients with LARC treated with TNT. EXPERIMENTAL DESIGN: The GEMCAD 1402 was a phase II randomized, multicentric clinical trial that randomized 180 patients with LARC to modified schedule of fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) +/- aflibercept, followed by chemoradiation and surgery. Plasma samples were collected at baseline and after TNT within 48 hours before surgery (presurgery). An ultrasensitive assay that integrates genomic and epigenomic cancer signatures was used to assess ctDNA status. ctDNA results were correlated with variables of local tumor response in the surgery sample, local/systemic recurrence, and survival. RESULTS: A total of 144 paired plasma samples from 72 patients were included. ctDNA was detectable in 83% of patients at baseline and in 15% following TNT (presurgery). No association was found between ctDNA status and pathologic response. Detectable presurgery ctDNA was significantly associated with systemic recurrence, shorter disease-free survival (HR, 4; P = 0.033), and shorter overall survival (HR, 23; P < 0.0001). CONCLUSIONS: In patients with LARC treated with TNT, presurgery ctDNA detected minimal metastatic disease identifying patients at high risk of distant recurrence and death. This study sets the basis for prospective clinical trials that use liquid biopsy to personalize the therapeutic approach following TNT.

T1 Rectal Adenocarcinoma: a Different Way to Measure Tumoral Invasion Based on the Healthy Residual Submucosa with Its Prognosis and Therapeutic Implications.

BACKGROUND: Surgical treatment of early rectal cancer T1 is either local excision or total mesorectal excision. The choice of surgery is based on the risk of metastatic lymph node involvement. The most important factor to consider is the degree of submucosal invasion. We present a different way to measure tumoral invasion derived from the measurement of the healthy residual submucosa with its prognosis and therapeutic implications METHODS: Observational study of tumor submucosal invasion in patients undergoing transanal endoscopic microsurgery was conducted. Parameters evaluated are submucosal invasion, measuring the healthy residual submucosa at the point of maximum invasion; macroscopic morphology of the tumor; presence of muscularis mucosa, muscularis propria, and measurement of submucosa in the tumor area and the healthy area. The classification proposed is compared with the ones previously published. RESULTS: Eighty consecutive patients diagnosed with T1 rectal cancer underwent transanal endoscopic microsurgery. Seventeen tumors (21.3%) were polypoid. En bloc resection was achieved in 77 (96.3%). The muscularis mucosa was present in 28 (35%), and the muscularis propria in 77 (96.3%) (p < 0.001). The healthy residual submucosa in the tumor area measured 2,343 ± 1,869 µm. Agreement was moderate with the Kikuchi classification (kappa 0.58) and very good with the Kudo classification (kappa 0.87). CONCLUSIONS: We describe a method for measuring submucosal invasion in T1 rectal cancer which does not depend on the morphology of the lesion or on the presence of the muscularis mucosa. It can be applied to all T1 classifications of the digestive tract in which the muscularis propria is present.

Completion Surgery in Unfavorable Rectal Cancer after Transanal Endoscopic Microsurgery: Does It Achieve Satisfactory Sphincter Preservation, Quality of Total Mesorectal Excision Specimen, and Long-term Oncological Outcomes?

BACKGROUND: Unfavorable adenocarcinoma after transanal endoscopic microsurgery requires "completion surgery" with total mesorectal excision. The literature on this procedure is very limited. OBJECTIVE: This study aims to assess the percentage of transanal endoscopic microsurgery that will require completion surgery. DESIGN: This is an observational study with prospective data collection and retrospective analysis from patients who were operated on consecutively. SETTINGS: The study was conducted at a single academic institution. PATIENTS: Patients undergoing transanal endoscopic microsurgery from June 2004 to December 2018 who later required total mesorectal excision were included. MAIN OUTCOME MEASURES: All the patients followed the same protocol: preoperative study, indication of transanal endoscopic microsurgery with curative intent, performance of transanal endoscopic microsurgery, and completion surgery indication 3 to 4 weeks after transanal endoscopic microsurgery. RESULTS: Seven hundred seventy-four patients underwent transanal endoscopic microsurgery, 622 with curative intent (group I: adenoma, 517; group II: adenocarcinoma, 105). Completion surgery was indicated in 64 of 622 (10.3%) patients: group I, 40 of 517 (7.7%) and group II, 24 of 105 (22.9%). After applying exclusion criteria, completion surgery was performed in 55 patients (8.8%). Abdominoperineal resection was performed in 23 (45.1%); the initial lesion was within 6 cm of the anal verge in 19 of these 23 (82.6%). The clinical morbidity rate (Clavien Dindo> II) was 3 of 51 (5.9%). Total mesorectal excision was graded as complete in 42 of 49 (85.7%). The circumferential resection margin was tumor-free in 47 of 50 (94%). Median follow-up was 58 months. Local recurrence was recorded in 2 of 51 (3.9%) and systemic recurrence was recorded in 7 of 51 (13.7%); 5-year disease-free survival was 86%. LIMITATIONS: The limitations are defined by the study's observational design and the retrospective analysis. CONCLUSION: The indication of completion surgery after transanal endoscopic microsurgery is low, but is higher in the indication of adenocarcinoma. Compared with initial total mesorectal excision, completion surgery requires a higher rate of abdominoperineal resection, but has similar postoperative morbidity, total mesorectal excision quality, and oncological results. See Video Abstract at http://links.lww.com/DCR/B423. CIRUGA COMPLEMENTARIA EN CNCER DE RECTO DESFAVORABLE DESPUS DE UNA TEM SE OBTIENE SATISFACTORIAMENTE PRESERVACIN DEL ESFNTER, CALIDAD DE MUESTRA DE ETM Y RESULTADOS ONCOLGICOS A LARGO PLAZO: ANTECEDENTES:El adenocarcinoma con evolución desfavorable luego de una de microcirugía endoscópica transanal (TEM) requiere "cirugía de finalización" con la excisión total del mesorecto. La literatura sobre este procedimiento es muy limitada.OBJETIVO:Evaluar el porcentaje de microcirugía endoscópica transanal que requerió cirugía completa.DISEÑO:Estudio observacional con recolección prospectiva de datos y análisis retrospectivo de pacientes operados consecutivamente.AJUSTES:El estudio se realizó en una sola institución académica.PACIENTES:Aquellos pacientes sometidos a microcirugía endoscópica transanal desde junio de 2004 hasta diciembre de 2018 que luego requirieron excisón toztal del mesorecto.PRINCIPALES MEDIDAS DE RESULTADO:Todos los pacientes siguieron el mismo protocolo: estudio preoperatorio, indicación de microcirugía endoscópica transanal con intención curativa, realización de microcirugía endoscópica transanal e indicación de cirugía complementaria 3-4 semanas después de la microcirugía endoscópica transanal.RESULTADOS:Setecientos setenta y cuatro pacientes fueron sometidos a microcirugía endoscópica transanal, 622 con intención curativa (grupo I, adenoma: 517, grupo II, adenocarcinoma: 105). la cirugía complementaria fué indicada en 64/622 (10.3%), grupo I: 40/517 (7.7%) y grupo II 24/105 (22.9%). Después de aplicar los criterios de exclusión, la cirugía complementaria se realizó en 55 pacientes (8,8%). La resección abdominoperineal fué realizada en 23 (45,1%); en 19 de estos casos 23 (82,6%) la lesión inicial se encontraba dentro los 6 cm del margen anal. La tasa de morbilidad clínica (Clavien-Dindo > II) fue de 3/51 (5,9%). La excisión total del mesorecto se calificó como completa en 42/49 (85,7%). El margen de resección circunferencial se encontraba libre de tumor en 47/50 (94%). La mediana de seguimiento fue de 58 meses. La recurrencia local se registró en 2/51 (3.9%) y la recurrencia sistémica en 7/51 (13.7%); La supervivencia libre de enfermedad a 5 años fue del 86%.LIMITACIONES:Todas definidas por el diseño observacional y el análisis retrospectivo del mismo.CONCLUSIÓN:La indicación de completar la cirugía después de una TEM es baja, pero es más alta cuando la indicación es por adenocarcinoma. En comparación con la excisión total del mesorecto inicial, la cirugía complementaria requiere una tasa más alta de resección abdominoperineal, pero tiene una morbilidad postoperatoria, una calidad de excisión total del mesorecto y resultados oncológicos similares. ConsulteVideo Resumen en http://links.lww.com/DCR/B423. (Traducción-Dr. Xavier Delgadillo).

Phase II randomized trial of capecitabine with bevacizumab and external beam radiation therapy as preoperative treatment for patients with resectable locally advanced rectal adenocarcinoma: long term results.

BACKGROUND: Preoperative chemoradiotherapy with capecitabine is considered as a standard of care for locally advanced rectal cancer. The "Tratamiento de Tumores Digestivos" group (TTD) previously reported in a randomized Ph II study that the addition of Bevacizumab to capecitabine-RT conferred no differences in the pre-defined efficacy endpoint (pathological complete response). We present the follow-up results of progression-free survival, distant relapse-free survival, and overall survival data at 3 and 5 years. METHODS: Patients (pts) were randomized to receive 5 weeks of radiotherapy (45 Gy/25 fractions) with concurrent Capecitabine 825 mg/m2 twice daily, 5 days per week with (arm A) or without (arm b) bevacizumab (5 mg/kg once every 2 weeks). RESULTS: In our study, the addition of bevacizumab to capecitabine and radiotherapy in the neoadjuvant setting shows no differences in pathological complete response (15.9% vs 10.9%), distant relapse-free survival (81.0 vs 80.4 and 76.2% vs 78.2% at 3 and 5 years respectively), disease-free survival (75% vs 71.7 and 68.1% vs 69.57% at 3 and 5 years respectively) nor overall survival at 5-years of follow-up (81.8% vs 86.9%). CONCLUSIONS: the addition of bevacizumab to capecitabine plus radiotherapy does not confer statistically significant advantages neither in distant relapse-free survival nor in disease-free survival nor in Overall Survival in the short or long term. TRIAL REGISTRATION: EudraCT number: 2009-010192-24 . Clinicaltrials.gov number: NCT01043484 .