RP leads to better survival vs radiation from time of metastasis

Compared with local radiation therapy (RT), radical prostatectomy (RP) as primary treatment for prostate cancer may result in a lower risk of castration-resistant disease and superior overall survival (OS) from the time of metastasis.

In a retrospective analysis of a nationwide database of men who had undergone prior RT or surgery for localized prostate cancer, those who received radiation were found to have a 32% adjusted higher risk of developing a castration-resistant state compared with those undergoing RP, reported Mohammed Shahait, MBBS, in a poster presented at the American Urological Association 2020 Virtual Experience.

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 Flatiron Health electronic health record–derived database, which includes about 2.5 million patients with cancer.

“Metastatic prostate cancer is a heterogeneous disease and includes men with de novo metastases upon presentation and a subgroup who present with local disease who underwent a local treatment and then progress to metastasis,” said Shahait, who was a 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, we aimed to study only patients who received local treatment and progressed to metastases to have a more homogeneous cohort.”

The cohort consisted of 664 patients who had received prior RP with or without adjuvant radiation (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, patients in the RP group were 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 greater than or equal to 8 (64.5% vs 54.5%; P = .0089). The men in the PR group also had lower PSA levels at the time of metastasis compared with those in the radiation group (6.4 vs 17.2 ng/mL; P <.0001). The group treated with radiation was more likely to receive androgen-deprivation therapy (ADT) before metastasis compared with the RP group (76% vs 60.7%; P <.0001).

The association between prior local treatment and progression to castration-resistant state and OS was tested, adjusting for age, race, PSA level, Gleason score, castration-resistant state, 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 a urology consultant at King Hussein Cancer Center, Amman, Jordan.

Median follow-up from the date of metastasis was 30 months for the RP group and 29.4 months for the radiation group. The unadjusted hazard ratio for castration-resistant state in the group that received radiation 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 radiation 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 support the benefit of extirpation of the primary disease on OS after developing metastatic disease, the researchers 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 development of castration-resistant tumors, leading to a worse outcome, Shahait said.