Impact of Total Neoadjuvant Therapy vs. Standard Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis of Randomized Trials.

Multimodality treatment is a standard of care for LARC, but the optimal sequencing of the treatment modalities remains unclear. Several randomized clinical trials (RCTs) compared total neoadjuvant treatment (TNT) vs. standard neoadjuvant chemoradiotherapy (CRT) with inconsistent results. A systematic review and meta-analysis was performed to evaluate the efficacy of TNT in terms of complete pathological response (pCR) rate, disease-free and overall survival vs. standard CRT in LARC. A systematic search was performed through MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and meeting abstracts up to May 2020. RCTs comparing CRT vs. TNT followed by surgery in LARC were eligible for the study. Study selection and data extraction were done following PRISMA guidelines by two independent reviewers. The Mantel-Haenzel method was used to obtain a fixed-effects model of pooled odds or hazard ratios for the main outcomes. Eight RCTs, including 2301 patients, met the eligibility criteria. TNT significantly improved pCR rate (OR = 1.99, 95% confidence interval (CI) 1.59-2.49; p < 0.001), 3-year disease-free-survival (DFS) (HR = 0.82, 95%CI 0.71-0.95; p = 0.01) and 3-year overall survival (OS) (hazard ratio (HR) = 0.81, p = 0.04). Grade 3-4 adverse events were not significantly different in both strategies (OR = 1.58; p = 0.14). An improved pCR rate was documented regardless of the type of radiotherapy administered (long vs. short fractionation schedules). No significant heterogeneity was found. The results of this meta-analysis show that TNT improves pCR and survival rates vs. standard preoperative CRT in patients with LARC. TNT may become a new standard of care in LARC, although longer follow-up is needed to properly assess its long-term impact on survival.

SEOM clinical guidelines for the adjuvant treatment of colorectal cancer.

Colorectal cancer is the third most common malignant neoplasm and the second cause of death by cancer in western countries. In this manuscript, the clinical guidelines of the Spanish Society of Medical Oncology (SEOM) for diagnosis and adjuvant treatment of colon cancer and rectal cancer are reported.

A panel discussion of controversies and challenges in the adjuvant treatment of colon cancer.

Current issues of adjuvant therapy for colon cancer concern the introduction of drugs other than fluorouracil-5/leucovorin (5-FU/LV), the benefits for stage II patients, the use of new primary endpoints and the influence of age on treatment benefits. These issues were addressed in a panel discussion and the conclusions were the following: FOLFOX4 is the first regimen that shows superiority over 5-FU/LV. The use of 3-year disease-free survival as primary endpoint could encourage the quicker adoption of improved therapeutic strategies into clinical practice. Available data suggest that there are some benefits for stage II patients, and the decision needs to be individualised for each patient. Further, therapeutic decisions based solely on the patient's age are inappropriate, and geriatric assessment tools will help in making this decision. This information would improve patient and physician understanding of the recent data regarding the potential benefits of adjuvant therapy.

A panel discussion of controversies and challenges in the adjuvant treatment of colon cancer

Las controversias actuales referentes al tratamiento adyuvante del cáncer de colon incluyen la introducción de fármacos más allá de 5-FU/LV, el beneficio que ofrece a los pacientes con estadio II, el uso de nuevas variables y la influencia de la edad sobre los beneficios del tratamiento. Estas controversias fueron discutidas en un panel de expertos y las conclusiones fueron las siguientes: FOLFOX4 es el primer régimen que ha demostrado superioridad frente a 5-FU/LV. El uso de la supervivencia libre de enfermedad a 3 años como variable principal de los estudios podrá permitir una adopción más rápida de estrategias terapéuticas. Los datos disponibles sugieren que existe beneficio para los pacientes con estadio II, y la decisión terapéutica debe ser individualizada. Finalmente, también se llegó a la conclusión de que las decisiones basadas únicamente en la edad no son apropiadas, y las herramientas de valoración geriátrica servirán de apoyo. Esta información puede mejorar el entendimiento de pacientes y médicos acerca de los datos recientes relativos a los beneficios del tratamiento adyuvante

Current issues of adjuvant therapy for colon cancer concern the introduction of drugs other than fluorouracil-5/leucovorin (5-FU/LV), the benefits for stage II patients, the use of new primary endpoints and the influence of age on treatment benefits. These issues were addressed in a panel discussion and the conclusions were the following: FOLFOX4 is the first regimen that shows superiority over 5-FU/LV. The use of 3-year disease-free survival as primary endpoint could encourage the quicker adoption of improved therapeutic strategies into clinical practice. Available data suggest that there are some benefits for stage II patients, and the decision needs to be individualised for each patient. Further, therapeutic decisions based solely on the patient's age are inappropriate, and geriatric assessment tools will help in making this decision. This information would improve patient and physician understanding of the recent data regarding the potential benefits of adjuvant therapy

Tratamiento adyuvante y resultados / Adjuvant treatment and results

Aproximadamente el 50 per cent de los pacientes tratados con cirugía con intención curativa fallecerán por recurrencia del cáncer colorrectal. La quimioterapia (QT) adyuvante aumenta la supervivencia libre de enfermedad y la supervivencia global en el estadio III del cáncer de colon, y es controvertida en el estadio II, salvo en pacientes de alto riesgo. Actualmente el 5fluorouracilo (5-FU) y leucovorín (LV), administrado por vía intravenosa durante 6 meses, se considera el régimen más adecuado. No existe ninguna opción terapéutica estándar tras la resección de metástasis, pero en la práctica clínica diaria se suele emplear 5FU/LV durante 6 meses. En metástasis hepáticas irresecables de inicio, la QT neoadyuvante logra una reducción del tamaño del tumor y permite resecciones completas en casos seleccionados. Los pacientes ancianos con buen estado general pueden beneficiarse de la QT igual que los más jóvenes. En estadios II y III de cáncer de recto, la administración postoperatoria de radioterapia pélvica y quimioterapia basada en 5-FU disminuye la recidiva local y aumenta la supervivencia. La eficacia de nuevos citostáticos, como las fluoropirimidinas orales (UFT, capecitabina), raltitrexed, irinotecán y oxaliplatino, se está estudiando en ensayos clínicos aleatorizados. La identificación de nuevos factores pronósticos permitirá seleccionar a subgrupos de mayor riesgo que puedan necesitar terapias más agresivas (AU)