Results presented at the American Urological Association 2020 Virtual Meeting demonstrated that of men who received prior RT or surgery for localized prostate cancer, those that had RT were found to have a 32% higher risk of developing castrate-resistant disease.
Compared with local radiation therapy (RT), radical prostatectomy (RP) as primary treatment for prostate cancer may result in a lower risk of castrate-resistant disease and superior overall survival (OS) from the time of metastasis.
In a retrospective analysis of a nationwide database of men who had received prior RT or surgery for localized prostate cancer, those who received RT were found to have a 32% adjusted higher risk of developing castrate-resistant disease compared with the RP group, reported Mohammed Shahait, MD, in a poster presented at the American Urological Association 2020 virtual meeting.
On multivariable analysis, after developing metastatic disease, mortality was significantly higher among the men who received RT alone versus those who underwent RP (P = .0013).
The findings come from an examination of the database derived from the Flatiron Health electronic health record, which includes about 2.5 million patients with cancer.
“Metastatic prostate cancer is a heterogeneous disease. [Patients] include men with de novo metastases upon presentation [and men] who [originally] presented with local disease, underwent a local treatment, and then progressed to metastases,” said Shahait, who was clinical instructor in urology at the University of Pennsylvania in Philadelphia at the time of the study. “Most of the data in the literature mix these patient groups when assessing outcomes, and we believe that it’s wrong from a biologic point of view. Therefore, to have a more homogeneous cohort, we aimed to study only patients who received local treatment and progressed to metastases.”
The cohort consisted of 664 patients who had received prior RP with or without adjuvant RT (n = 310) or RT alone (n = 354) for local disease and had progressed to metastatic disease between 2010 and 2018.
At the time of metastasis, the RP group was younger (63.8 ± 7.25 vs 69.3 ± 7.67 years; P <.0001), had a lower prostate-specific antigen (PSA) level at prostate cancer diagnosis (7.8 vs 10.9 ng/mL; P <.0001), and were more likely to have a Gleason score of 8 or higher (64.5% vs 54.5%; P =.0089). The RP group also had a lower PSA level at the time of metastasis compared with the RT group (6.4 vs 17.2 ng/mL; P <.0001). The group treated with RT was more likely to receive androgen deprivation therapy (ADT) before metastasis compared with the RP group (76.0% vs 60.7%; P <.0001).
The association between prior local treatment and progression to castrate-resistant disease and OS was tested, adjusting for age, race, PSA level, Gleason score, castrate-resistant disease, administration of ADT before metastasis, and treatment year.
“As urologists and radiation therapists, we don’t know what happens to all patients after metastasis because most of the management is led by medical oncologists. The focus here is to see what would happen after metastasis,” said Shahait, who is currently a consultant of urology at King Hussein Cancer Center, Amman, Jordan.
Median follow-up from the date of metastasis was 30.0 months for the RP group and 29.4 months for the RT group. The unadjusted hazard ratio for castrate-resistant disease in the group who received RT was 1.45 (P <.001). The association remained significant upon adjusting for patient- and disease-specific parameters (HR, 1.326; P = .0259).
On multivariable analysis, men who received RT alone had 77% higher overall mortality after developing metastatic disease (P = .0013) compared with men who underwent RP.
Notwithstanding the inherent selection bias at the time of choosing the type of local treatment because of unmeasured confounding variables, the results add to a growing body of evidence that supports the benefit of extirpation of the primary disease on OS after developing metastatic disease, the investigators concluded in their poster.
One theory for the finding is that early use of ADT as well as RT may potentiate epithelial-mesenchymal transition, which mediates tumor invasion, metastasis, and the development of castrate resistance, leading to worse outcomes, said Shahait.