Publication: Comparación de la respuesta completa tumoral y de los resultados quirúrgicos precoces en pacientes con cáncer de recto tratados con terapia neoadyuvante total frente a quimiorradioterapia convencional
Authors
Abellán Garay, Laura
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Escuelas::Escuela Internacional de Doctorado
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Lage Laredo, Ana María ; Calero García, Purificación
Publisher
Universidad de Murcia
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DOI
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info:eu-repo/semantics/doctoralThesis
Description
Abstract
Objetivos de la tesis: La terapia neoadyuvante total (TNT) ha surgido como una alternativa terapéutica a la quimiorradioterapia (LCRT) convencional en el tratamiento del cáncer localmente avanzado de recto (LARC), al permitir la administración de la totalidad de la quimioterapia sistémica y la radioterapia en el contexto preoperatorio. Este enfoque busca mejorar el cumplimiento terapéutico y aumentar las tasas de respuesta patológica completa (pCR), sin incrementar la toxicidad del tratamiento ni las complicaciones postquirúrgicas, favoreciendo la implementación de estrategias de preservación de órgano en pacientes con respuesta clínica completa (cRC) o casi completa.
El objetivo principal de este estudio fue el de evaluar la respuesta completa (RC) tumoral, incluyendo la pCR y cRC, inducida por el esquema TNT, compararla con la obtenida con el esquema de LCRT convencional, además de analizar sus resultados quirúrgicos y postoperatorios precoces. Como objetivos secundarios se evaluaron la adherencia y la toxicidad de la radioterapia y la quimioterapia, los hallazgos anatomopatológicos y la duración global del tratamiento.
Metodología: Se realizó un estudio observacional multicéntrico con dos cohortes consecutivas de pacientes diagnosticados de LARC. La cohorte experimental fue prospectiva e incluyó pacientes tratados con TNT basada en radioterapia de ciclo corto seguida de 6 ciclos de CAPOX o 9 ciclos de FOLFOX de manera neoadyuvante con cirugía a las 5 – 8 semanas. La cohorte control, retrospectiva, recibió LCRT seguida de cirugía diferida (8 – 12 semanas) y quimioterapia adyuvante. En casos seleccionados del grupo TNT con cRC se propuso manejo con preservación de órgano.
Resultados: Se incluyeron 89 pacientes, 50 en el grupo control y 39 en el grupo experimental. Las características basales fueron similares, salvo por una mayor prevalencia de antecedentes neurológicos en el brazo TNT (p = 0.046). La RC no mostró diferencias significativas entre grupos (23.1% TNT frente al 30% LCRT, p = 0.465). No obstante, la TNT alcanzó una mayor calidad del mesorrecto, con un mesorrecto completo en el 83.8% del grupo experimental frente al 62% del grupo control, p = 0.002. Ambos esquemas presentaron una adherencia a la quimioterapia y la radioterapia y un perfil de toxicidad similares, salvo por una mayor incidencia de cistitis rádica en el grupo LCRT (2.6% TNT versus 20% LCRT, p = 0.02). En cuanto a los resultados quirúrgicos, en el grupo TNT se realizaron menos estomas (73% TNT frente al 90% LCRT) y en concreto menos ileostomías de protección (32.5% versus 62%), sin implicar un aumento en la dehiscencia de la anastomosis (4.5% TNT versus 13.9% LCRT, p = 0.392). Postoperatoriamente, los pacientes tratados con TNT presentaron menos reingresos en los primeros 30 días (5.4% versus 20%, p = 0.049), sin diferencias estadísticamente significativas en cuanto a estancia hospitalaria, reintervenciones ni en el resto de complicaciones quirúrgicas precoces. Por último, la duración global del tratamiento fue significativamente menor en el grupo TNT (25.46 ± 3.57 semanas frente a 37.72 ± 3.79 semanas, p < 0.001).
Conclusiones: La terapia neoadyuvante total no logró una diferencia significativa en la respuesta completa tumoral, pero se asoció a una menor necesidad de estomas, a mayor calidad del mesorrecto, a una reducción de los reingresos y a una duración global del tratamiento significativamente menor, manteniendo un perfil de toxicidad similar. Estos hallazgos refuerzan su viabilidad como una alternativa terapéutica segura, eficaz y clínicamente aplicable en el abordaje del LARC.
Aims of the thesis: Total neoadjuvant therapy (TNT) has emerged as a therapeutic alternative to conventional chemoradiotherapy (LCRT) for the treatment of locally advanced rectal cancer (LARC), as it allows the administration of full-dose chemotherapy and radiotherapy prior to surgery. This approach seeks to improve treatment compliance and increase pathological complete response (pCR) rates, without increasing treatment-related toxicity or postoperative complications, thus facilitating the implementation of organ preservation strategies in patients who reach clinical complete response (cRC) or near-complete response. The aim of this study was to evaluate complete tumor response (RC), including both pCR and cRC, induced by TNT; to compare it with the results of the conventional LCRT regimen; and to analyze early surgical and postoperative outcomes. Secondary objectives included the assessment of radiotherapy and chemotherapy compliance and toxicity, pathological findings, and total treatment duration. Methods: A multicenter observational study was conducted with two consecutive cohorts of patients diagnosed with LARC. The experimental cohort was prospective and included patients treated with TNT consisting of short-course radiotherapy followed by 6 cycles of CAPOX or 9 cycles of FOLFOX as neoadjuvant treatment, with surgery planned 5 – 8 weeks later. The control cohort was retrospective and received LCRT followed by delayed surgery (8 – 12 weeks) and adjuvant chemotherapy. In selected cases from the TNT group who achieved cRC, an organ preservation approach was proposed. Results: A total of 89 patients were included, 50 in the control group and 39 in the experimental group. Baseline characteristics were similar, except for a higher prevalence of neurological comorbidities in the TNT arm (p = 0.046). RC did not differ significantly between groups (23.1% TNT versus 30% LCRT, p = 0.465). However, TNT was associated with improved mesorectal specimen quality, with complete mesorectal excision achieved in 83.8% of the experimental group compared to 62% in the control group (p = 0.002). Both regimens showed similar compliance with chemotherapy and radiotherapy and comparable toxicity profiles, except for a higher incidence of radiation-induced cystitis in the LCRT group (2.6% TNT versus 20% LCRT, p = 0.02). Regarding surgical outcomes, fewer stomas were created in the TNT group (73% versus 90%), specifically fewer protective ileostomies (32.5% versus 62%), without an increase in anastomotic leak rates (4.5% TNT versus 13.9% LCRT, p = 0.392). Postoperatively, patients treated with TNT had fewer readmissions within the first 30 days (5.4% compared to 20%, p = 0.049), with no statistically significant differences in hospital stay, reoperations, or other early surgical complications. Finally, total treatment duration was significantly shorter in the TNT group (25.46 ± 3.57 weeks versus 37.72 ± 3.79 weeks, p < 0.001). Conclusions: Total neoadjuvant therapy did not achieve a significant difference in complete tumor response, but it was associated with a reduced need for stomas, improved mesorectal specimen quality, fewer readmissions, and a significantly shorter overall treatment duration, while maintaining a comparable toxicity profile. These findings support TNT as a safe, effective, and clinically feasible therapeutic alternative in the management of LARC.
Aims of the thesis: Total neoadjuvant therapy (TNT) has emerged as a therapeutic alternative to conventional chemoradiotherapy (LCRT) for the treatment of locally advanced rectal cancer (LARC), as it allows the administration of full-dose chemotherapy and radiotherapy prior to surgery. This approach seeks to improve treatment compliance and increase pathological complete response (pCR) rates, without increasing treatment-related toxicity or postoperative complications, thus facilitating the implementation of organ preservation strategies in patients who reach clinical complete response (cRC) or near-complete response. The aim of this study was to evaluate complete tumor response (RC), including both pCR and cRC, induced by TNT; to compare it with the results of the conventional LCRT regimen; and to analyze early surgical and postoperative outcomes. Secondary objectives included the assessment of radiotherapy and chemotherapy compliance and toxicity, pathological findings, and total treatment duration. Methods: A multicenter observational study was conducted with two consecutive cohorts of patients diagnosed with LARC. The experimental cohort was prospective and included patients treated with TNT consisting of short-course radiotherapy followed by 6 cycles of CAPOX or 9 cycles of FOLFOX as neoadjuvant treatment, with surgery planned 5 – 8 weeks later. The control cohort was retrospective and received LCRT followed by delayed surgery (8 – 12 weeks) and adjuvant chemotherapy. In selected cases from the TNT group who achieved cRC, an organ preservation approach was proposed. Results: A total of 89 patients were included, 50 in the control group and 39 in the experimental group. Baseline characteristics were similar, except for a higher prevalence of neurological comorbidities in the TNT arm (p = 0.046). RC did not differ significantly between groups (23.1% TNT versus 30% LCRT, p = 0.465). However, TNT was associated with improved mesorectal specimen quality, with complete mesorectal excision achieved in 83.8% of the experimental group compared to 62% in the control group (p = 0.002). Both regimens showed similar compliance with chemotherapy and radiotherapy and comparable toxicity profiles, except for a higher incidence of radiation-induced cystitis in the LCRT group (2.6% TNT versus 20% LCRT, p = 0.02). Regarding surgical outcomes, fewer stomas were created in the TNT group (73% versus 90%), specifically fewer protective ileostomies (32.5% versus 62%), without an increase in anastomotic leak rates (4.5% TNT versus 13.9% LCRT, p = 0.392). Postoperatively, patients treated with TNT had fewer readmissions within the first 30 days (5.4% compared to 20%, p = 0.049), with no statistically significant differences in hospital stay, reoperations, or other early surgical complications. Finally, total treatment duration was significantly shorter in the TNT group (25.46 ± 3.57 weeks versus 37.72 ± 3.79 weeks, p < 0.001). Conclusions: Total neoadjuvant therapy did not achieve a significant difference in complete tumor response, but it was associated with a reduced need for stomas, improved mesorectal specimen quality, fewer readmissions, and a significantly shorter overall treatment duration, while maintaining a comparable toxicity profile. These findings support TNT as a safe, effective, and clinically feasible therapeutic alternative in the management of LARC.
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