Abstract

Fernando Lopez Campos¹, David Lorente², Casilda Llacer-Pérez³, Iván Henríquez⁴, Paula Peleteiro⁵, Alfonso Gómez-Iturriaga⁶, Miguel Ramírez-Backhaus⁷, Sara Álvarez⁸, Teresa Alonso-Gordoa⁹, Javier Molina-Cerrillo⁹, Carmen Vallejo¹, Asunción Hervás¹, Joaquín Navarro-Castellón¹⁰, Junior Gómez⁴, Virginia Morillo¹¹, Rebeca Lozano¹², Nuria Romero-Laorden¹³, Raquel García¹⁴, Antonio Hernández-Corrales¹, Lira Pelari¹, Carlos Ferrer-Albiach¹⁵, Sonsoles Sancho¹, Elena Castro¹⁶, David Olmos¹²

¹Hospital Universitario Ramón y Cajal, Radiation Oncology, Madrid, Spain; ²Hospital Provincial de Castellón, Medical Oncology, Castellón, Spain; ³Hospital Virgen de la Victoria y Regional de Málaga, Medical Oncology, Málaga, Spain; ⁴Hospital Universitario Sant Joan de Reus, Radiation Oncology, Reus, Spain; ⁵Hospital Clínico Universitario de Santiago de Compostela, Radiation Oncology, Santiago de Compostela, Spain; ⁶Hospital Universitario de Cruces, Radiation Oncology, Baracaldo, Spain; ⁷Instituto Valenciano de Oncología, Urology, Valencia, Spain; ⁸Hospital Universitario Ramón y Cajal, Urology, Madrid, Spain; ⁹Hospital Universitario Ramón y Cajal, Medical Oncology, Madrid, Spain; ¹⁰Hospital Central de la Defensa Gómez Ulla, Radiation Oncology, Madrid, Spain; ¹¹Hospital Provincial de Castellón, Radiation oncology, Castellón, Spain; ¹²Centro Nacional de Investigaciones Oncológicas, Prostate Cancer Unit, Madrid, Spain; ¹³Hospital Universitario La Princesa, Medical Oncology, Madrid, Spain; ¹⁴Hospital Clínico Universitario de Valencia, Radiation Oncology, Madrid, Spain; ¹⁵Hospital Provincial de Castellón, Radiation Oncology, Castellón, Spain; ¹⁶Instituto de Investigación Biomédica de Málaga, Medical Oncology, Málaga, Spain

In metastatic castration-resistant prostate cancer (mCRPC) patients, retrospective analyses have noted an association between previous local treatment to the primary tumour and improved overall survival (OS). Variations in PSA levels in mCRPC are widely used in the monitoring of response to treatment with Abiraterone or Enzalutamide (Abi/Enza), although it has not been validated as an early biomarker for OS. We aimed to evaluate the significance of the previous local treatment to the primary tumor and early PSA changes in Abi/Enz-treated mCRPC patients.

We retrospectively evaluated Abi/Enz-treated mCRPC patients from 11 hospitals between 2011-2020. A descriptive and multivariate analysis of the data was carried out in order to establish the association of local treatment to the primary tumor and PSA variations at 4 and 12 weeks (expressed as 25% modifications, relative to baseline value at the start of Abi/Enz) with OS. Association with OS was analyzed using multivariate Cox regression and log-rank analyses. Spearman’s rho correlation coefficient (r) was calculated to evaluate the association between PSA changes at 4 and 12 weeks.

We analyzed 640 mCRPC patients with a median follow-up of 30.2 months. Patients with previous local treatment to the primary tumor presented greater OS than untreated, HR 0.79 (0.64-0.96), p=0.02, without significant differences depending on the type of local treatment, radiotherapy (28.42 months; HR 0.97 (0.67-1.4), p=0.867 and prostatectomy followed by postoperative radiotherapy (31.34 months; HR 0.74 (0.48-1.13), p=0.164. We found a detriment OS in patients with a 25% PSA rise at 4 weeks, (20.57 vs 28.78 months; HR 1.66 (1.3-2.13), p<0.001) and a 25% confirmed PSA increase at 12 weeks after starting treatment (15,87 vs 31,61 months; HR 2.64 (2.06-3.39) p<0.001). The percentage PSA decline at 4 weeks was significantly correlated with the percentage PSA change at 12 weeks (r.0.821; p<0.001). 

Local treatment to the primary tumor can be established as a prognostic factor in mCRPC. PSA changes as early as 4 weeks after Abi/Enza initiation are highly associated with OS in mCPRC. Prospective multicentre validation studies are needed to confirm these findings.