Publication: Análisis pronóstico de los factores relacionados con la morbimortalidad y la supervivencia tras una citorreducción de intervalo completa en pacientes con cáncer de ovario
Authors
Alcaraz Solano, Ángela
item.page.secondaryauthor
Escuela Internacional de Doctorado
item.page.director
Cascales Campos, Pedro Antonio
Publisher
Universidad de Murcia
publication.page.editor
publication.page.department
DOI
item.page.type
info:eu-repo/semantics/doctoralThesis
Description
Abstract
Introducción. El cáncer de ovario avanzado continúa siendo la neoplasia ginecológica de mayor mortalidad, debido a su diagnóstico tardío y a su tendencia a la diseminación peritoneal. Aunque la citorreducción macroscópica completa es el principal factor pronóstico modificable, la recaída sigue siendo frecuente incluso tras una cirugía óptima, lo que evidencia el papel de la enfermedad microscópica residual. En este contexto, la quimioterapia intraperitoneal hipertérmica (HIPEC) se plantea como una estrategia locorregional dirigida al compartimento peritoneal. Sin embargo, persisten incertidumbres sobre la selección de pacientes, el valor pronóstico del índice de carcinomatosis peritoneal (PCI) y el impacto diferencial del fármaco empleado. El objetivo fue analizar los factores asociados a supervivencia libre de enfermedad y supervivencia global en pacientes con cáncer de ovario avanzado tratadas mediante quimioterapia neoadyuvante, cirugía citorreductora de intervalo completa e HIPEC, evaluando además morbimortalidad e influencia del esquema cisplatino frente a paclitaxel.Pacientes y metodología. Se realizó un estudio multicéntrico retrospectivo que incluyó 293 pacientes diagnosticadas de carcinoma seroso de alto grado de ovario en estadios FIGO IIIC-IV, tratadas entre enero de 2010 y mayo de 2023 en cuatro centros españoles con experiencia en cirugía oncológica peritoneal avanzada. Todas recibieron quimioterapia neoadyuvante basada en platino y cirugía citorreductora de intervalo, incluyéndose únicamente aquellas con citorreducción macroscópica completa (CC-0). Tras la cirugía se administró HIPEC mediante técnica cerrada, con cisplatino o paclitaxel según protocolo. Se analizaron variables clínicas, tumorales, intraoperatorias, postoperatorias y de supervivencia mediante estadística descriptiva, curvas de Kaplan-Meier y modelos multivariantes.Resultados. La mediana de edad fue de 62 años y la mediana de PCI de 9. Un 36,5% de las pacientes precisó al menos una resección intestinal. Recibieron cisplatino 138 pacientes y paclitaxel 155. Ambos grupos fueron comparables en variables clínicas basales, aunque el grupo paclitaxel presentó mayor carga tumoral y complejidad quirúrgica, con PCI más elevado, mayor proporción de estadio FIGO IV, mayor tiempo operatorio y mayor necesidad de estoma. La tasa de complicaciones mayores fue del 20,1% y la mortalidad postoperatoria a 90 días fue baja, con 6 fallecimientos. El cisplatino se asoció de forma independiente con mayor riesgo de complicaciones mayores frente a paclitaxel, junto con edad y PCI. La mediana de supervivencia libre de enfermedad fue de 23 meses. El PCI >15 se asoció con mayor riesgo de recaída, mientras que paclitaxel se comportó como factor protector. La mediana fue de 25 meses con paclitaxel frente a 16 meses con cisplatino; en pacientes con PCI >15 fue de 19 frente a 13 meses. La supervivencia global mediana fue de 36 meses, con mejores resultados en el grupo paclitaxel.Discusión. Los resultados muestran que la citorreducción completa, aunque imprescindible, no agota la explicación pronóstica del cáncer de ovario avanzado. El PCI mantiene un papel central incluso en pacientes CC-0, sugiriendo que la carga tumoral inicial refleja extensión anatómica y agresividad biológica. La asociación favorable del paclitaxel intraperitoneal, observada pese a su empleo en pacientes de mayor complejidad, cuestiona la consideración de la HIPEC como intervención uniforme y sugiere que el agente administrado puede influir en el control de la enfermedad microscópica residual. Además, la relación entre complicaciones mayores, retraso de la adyuvancia y peor supervivencia subraya que la calidad del postoperatorio forma parte del resultado oncológico.Conclusiones. En pacientes con cáncer de ovario avanzado tratadas con quimioterapia neoadyuvante, citorreducción completa e HIPEC, el PCI se confirma como determinante pronóstico fundamental. Paclitaxel se asoció a mejores resultados oncológicos que cisplatino, sin incremento de morbimortalidad, con beneficio especialmente evidente en pacientes con mayor carga tumoral. Estos hallazgos apoyan una estrategia locorregional individualizada, integrando carga tumoral, fármaco intraperitoneal, seguridad perioperatoria y continuidad del tratamiento sistémico.
Introduction. Advanced ovarian cancer remains the gynaecological malignancy with the highest mortality, mainly because of its late diagnosis and marked tendency to disseminate throughout the peritoneal cavity. Although complete macroscopic cytoreduction is the main modifiable prognostic factor, relapse remains frequent even after optimal surgery, highlighting the clinical relevance of residual microscopic disease. In this context, hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a locoregional strategy directed at the peritoneal compartment. However, uncertainties remain regarding patient selection, the prognostic value of the peritoneal carcinomatosis index (PCI), and the differential impact of the drug used during intraperitoneal perfusion. The aim of this thesis was to analyse the factors associated with disease-free survival and overall survival in patients with advanced ovarian cancer treated with neoadjuvant chemotherapy, complete interval cytoreductive surgery, and HIPEC, while also assessing postoperative morbidity and mortality and the influence of the HIPEC regimen, cisplatin versus paclitaxel. Patients and methodology. A retrospective multicentre study was conducted including 293 patients diagnosed with high grade serous ovarian carcinoma in advanced FIGO stages IIIC-IV, treated between January 2010 and May 2023 in four Spanish centres with experience in advanced peritoneal oncological surgery. All patients received platinum based neoadjuvant chemotherapy and subsequently underwent interval cytoreductive surgery; only patients in whom complete macroscopic cytoreduction (CC-0) was achieved were included. After surgery, HIPEC was administered using a closed technique, with either cisplatin or paclitaxel according to each centre's protocol. Clinical, tumour related, intraoperative, postoperative, and survival variables were analysed using descriptive statistics, Kaplan-Meier survival curves, and multivariable models.Results. The median age was 62 years and the median PCI was 9. At least one bowel resection was required in 36.5% of patients. HIPEC was performed with cisplatin in 138 patients and with paclitaxel in 155. Both groups were comparable in baseline clinical variables, although the paclitaxel group had a higher tumour burden and greater surgical complexity, reflected by a higher PCI, a higher proportion of FIGO stage IV disease, longer operative time, and a greater need for stoma formation. The major complication rate was 20.1%, and 90-day postoperative mortality was low, with 6 deaths. Cisplatin was independently associated with a higher risk of major complications compared with paclitaxel, together with age and PCI. Median disease-free survival was 23 months. PCI >15 was associated with a higher risk of relapse, whereas paclitaxel behaved as a protective factor. Median disease-free survival was 25 months with paclitaxel versus 16 months with cisplatin; among patients with PCI >15, it was 19 versus 13 months, respectively. Median overall survival was 36 months, with better outcomes in the paclitaxel group. Discussion. These results show that complete cytoreduction, although essential, does not fully explain prognosis in advanced ovarian cancer. PCI maintains a central prognostic role even in CC-0 patients, suggesting that initial tumour burden reflects not only anatomical extent but also biological aggressiveness. The favourable association observed with intraperitoneal paclitaxel, despite its use in more complex patients, challenges the concept of HIPEC as a uniform intervention and suggests that the administered agent may influence the control of residual microscopic disease. Furthermore, the relationship between major complications, delayed adjuvant therapy, and poorer survival underlines that postoperative quality is part of the oncological outcome. Conclusions. In patients with advanced ovarian cancer treated with neoadjuvant chemotherapy, complete cytoreduction, and HIPEC, PCI is confirmed as a fundamental prognostic determinant. Paclitaxel was associated with better oncological outcomes than cisplatin, without increased morbidity and mortality, with a particularly evident benefit in patients with higher tumour burden. These findings support an individualised locoregional strategy integrating tumour burden, intraperitoneal agent selection, perioperative safety, and continuity of systemic treatment.
Introduction. Advanced ovarian cancer remains the gynaecological malignancy with the highest mortality, mainly because of its late diagnosis and marked tendency to disseminate throughout the peritoneal cavity. Although complete macroscopic cytoreduction is the main modifiable prognostic factor, relapse remains frequent even after optimal surgery, highlighting the clinical relevance of residual microscopic disease. In this context, hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a locoregional strategy directed at the peritoneal compartment. However, uncertainties remain regarding patient selection, the prognostic value of the peritoneal carcinomatosis index (PCI), and the differential impact of the drug used during intraperitoneal perfusion. The aim of this thesis was to analyse the factors associated with disease-free survival and overall survival in patients with advanced ovarian cancer treated with neoadjuvant chemotherapy, complete interval cytoreductive surgery, and HIPEC, while also assessing postoperative morbidity and mortality and the influence of the HIPEC regimen, cisplatin versus paclitaxel. Patients and methodology. A retrospective multicentre study was conducted including 293 patients diagnosed with high grade serous ovarian carcinoma in advanced FIGO stages IIIC-IV, treated between January 2010 and May 2023 in four Spanish centres with experience in advanced peritoneal oncological surgery. All patients received platinum based neoadjuvant chemotherapy and subsequently underwent interval cytoreductive surgery; only patients in whom complete macroscopic cytoreduction (CC-0) was achieved were included. After surgery, HIPEC was administered using a closed technique, with either cisplatin or paclitaxel according to each centre's protocol. Clinical, tumour related, intraoperative, postoperative, and survival variables were analysed using descriptive statistics, Kaplan-Meier survival curves, and multivariable models.Results. The median age was 62 years and the median PCI was 9. At least one bowel resection was required in 36.5% of patients. HIPEC was performed with cisplatin in 138 patients and with paclitaxel in 155. Both groups were comparable in baseline clinical variables, although the paclitaxel group had a higher tumour burden and greater surgical complexity, reflected by a higher PCI, a higher proportion of FIGO stage IV disease, longer operative time, and a greater need for stoma formation. The major complication rate was 20.1%, and 90-day postoperative mortality was low, with 6 deaths. Cisplatin was independently associated with a higher risk of major complications compared with paclitaxel, together with age and PCI. Median disease-free survival was 23 months. PCI >15 was associated with a higher risk of relapse, whereas paclitaxel behaved as a protective factor. Median disease-free survival was 25 months with paclitaxel versus 16 months with cisplatin; among patients with PCI >15, it was 19 versus 13 months, respectively. Median overall survival was 36 months, with better outcomes in the paclitaxel group. Discussion. These results show that complete cytoreduction, although essential, does not fully explain prognosis in advanced ovarian cancer. PCI maintains a central prognostic role even in CC-0 patients, suggesting that initial tumour burden reflects not only anatomical extent but also biological aggressiveness. The favourable association observed with intraperitoneal paclitaxel, despite its use in more complex patients, challenges the concept of HIPEC as a uniform intervention and suggests that the administered agent may influence the control of residual microscopic disease. Furthermore, the relationship between major complications, delayed adjuvant therapy, and poorer survival underlines that postoperative quality is part of the oncological outcome. Conclusions. In patients with advanced ovarian cancer treated with neoadjuvant chemotherapy, complete cytoreduction, and HIPEC, PCI is confirmed as a fundamental prognostic determinant. Paclitaxel was associated with better oncological outcomes than cisplatin, without increased morbidity and mortality, with a particularly evident benefit in patients with higher tumour burden. These findings support an individualised locoregional strategy integrating tumour burden, intraperitoneal agent selection, perioperative safety, and continuity of systemic treatment.
Citation
item.page.embargo
Collections
Ir a Estadísticas
Este ítem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by-nc-nd/4.0/