Metastasis-Directed Therapy May Delay ADT in Advanced Prostate Cancer

Metastasis-directed therapy (MDT) in selected patients with recurrent oligometastatic prostate cancer led to PSA responses in a majority of patients and delayed initiation of hormonal therapy by 18 months, a retrospective study showed.

Overall, 77 of 124 patients had PSA declines of more than 50% with surgery or stereotactic body radiation therapy (SBRT). In particular, surgery led to PSA responses in 80.5% of patients, and almost a third of patients remained progression free after 3 years.

The results showed that local treatment of oligometastatic prostate cancer without androgen deprivation therapy (ADT) is feasible and warrants prospective investigation of the strategy, reported Jack R. Andrews, MD, of the Mayo Clinic in Phoenix, and colleagues, in the Journal of Urology.

“To our knowledge, this is the first report evaluating the impact of MDT alone in solitary metastatic prostate cancer and is one of the largest studies to evaluate surgical and radiotherapy MDT in the absence of ADT,” the authors said. “These results indicate that further investigation is needed to define the role of MDT in oligometastatic prostate cancer.”

The findings add to those of prior smaller studies suggesting a beneficial effect of MDT in oligometastatic prostate cancer. A phase II randomized trial of 62 patients showed that those assigned to MDT with surgery or SBRT had improved outcomes and delayed initiation of ADT versus surveillance. In another small randomized study, 54 patients with oligorecurrent disease were managed by SBRT or surveillance, and the MDT group had improved outcomes.

A single-center retrospective analysis of almost 500 patients with oligometastatic prostate cancer showed that MDT with surgery or external beam radiation therapy led to better outcomes in patients with lymph node metastasis as compared with ADT but not in those with bony metastasis.

Similar evidence exists for other types of cancer. For example, a recent study in mutated non-small cell lung cancer showed that MDT led to “clinically meaningful” extension of targeted therapy after progression.

Historically, metastatic prostate cancer has been considered incurable, and the default treatment has been systemic therapy. The emergence of oligometastatic disease as an intermediate between localized and disseminated metastatic disease has led to a “seismic shift” in clinical thinking, suggesting some patients might be cured by a combination of local and MDT. Whether MDT without ADT has a role in advanced prostate cancer remains controversial, and results with MDT have been biased by inclusion of patients who received ADT, according to Andrews’ group.

To examine MDT without ADT, investigators retrospectively identified 124 consecutive patients who had a solitary metachronous metastatic lesion identified by PET imaging and treated during 2008 to 2018. Patients with nodal metastases were treated with surgery (n=67). Patients who underwent pelvic lymphadenectomy did not receive pelvic irradiation. Those with bony metastases, as well as a few with lymph node metastases, received SBRT (n=57).

The primary outcome was PSA response, defined as >50% decline from pre-MDT to 3-month follow-up. Biochemical progression after MDT was defined as a PSA level >0.2 ng/mL on two consecutive assessments. Radiographic progression was defined as any new lesion identified by PET imaging. Investigators defined ADT as conventional hormonal therapy, surgical castration, or second-generation antiandrogens.

MDT achieved PSA responses in 62% of the patients, 80.5% with surgery and 40.3% with SBRT. Among patients treated surgically, 31 (46%) had a complete response, 23 (34%) had a good response (PSA decline of 50%-99%), and six (9%) had a partial response (≤49%). In the SBRT group, 11 (19%) had a complete PSA response, 12 (21%) had a good response, and 19 (33%) had a partial response.

The 3-year biochemical PFS 17.9% with surgery and 12.3% with SBRT. Median time to radiographic progression was 14.9 months with surgery and 9.5 months with SBRT.

Surgery delayed initiation of ADT for 18.5 months and SBRT for 17.5 months. Delay in initiation of ADT ranged from 8.4 to 44.7 months. Patients treated surgically had a 3-year median PFS of 29% as compared with 17.0% with SBRT.

Study limitations included the inherent selection bias associated with retrospective studies, use of C-11 choline PET imaging versus standard PET, and selection of patients most likely to benefit from MDT.

“Despite the limitation, the results characterize the outcomes and highlight the role of MDT without ADT,” the authors concluded. “Further high-quality, prospective studies are warranted to expand the selection criteria for MDT, define the roles of surgical and SBRT MDT, and assess the role of MDT in patients with de novo metastatic prostate cancer.”