For patients with high-risk localized or locally advanced prostate cancer (PCa), new phase 3 research suggests that perioperative use of apalutamide may be beneficial in patients undergoing radical prostatectomy and PSMA PET imaging played a key role in the evaluation of the androgen receptor inhibitor (ARI) for perioperative use.
For the randomized, double-blind, placebo-controlled PROTEUS trial, recently published in the New England Journal of Medicine, researchers reviewed data for 2,109 patients (median age of 66) drawn from 184 facilities in 18 countries. The study authors noted that 1,057 patients were treated with a combination of androgen deprivation therapy (ADT) and perioperative apalutamide and the remaining 1,052 patients had ADT and placebo.
There was no significantly statistical difference with respect to metastasis-free survival between the two cohorts based on conventional imaging alone (defined as MRI, computed tomography or bone scan), according to the researchers.
However, the researchers amended the study protocol to incorporate PSMA PET into the assessment of distant metastasis.
• Based on conventional imaging or PSMA PET, patients in the apalutamide group had a 32 percent reduction in the time to distant metastasis.
• The study authors found that 78.2 percent of the perioperative apalutamide group achieved five-year metastasis-free survival in comparison to 73.5 percent in the placebo group.
• The perioperative apalutamide cohort had a 20 percent lower risk of distant metastasis or death, according to the researchers.
“In our trial, the between-group difference in metastasis-free survival as assessed by conventional imaging alone was not significant. The increasing use of PSMA PET since the inception of our trial may limit the power of assessment of metastasis-free survival by conventional imaging alone in early-stage disease. PSMA PET is recommended for consideration in future trials to generate results relevant to clinical practice,” noted lead study author Mary-Ellen Taplin, MD, a professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, and colleagues.
Three Key Takeaways
- Perioperative apalutamide improves outcomes in high-risk prostate cancer. In patients with high-risk localized or locally advanced PCa undergoing radical prostatectomy, adding apalutamide to ADT resulted in a 20 percent lower risk of distant metastasis or death, a significantly longer event-free survival (57.1 vs. 38.4 months), and an approximately 31-month longer median time before needing subsequent therapy compared to placebo.
- PSMA PET is essential for accurate metastasis assessment. Conventional imaging alone (MRI, CT, bone scan) failed to show a statistically significant difference in metastasis-free survival between groups. Only after incorporating PSMA PET into the protocol did the 32 percent reduction in time to distant metastasis become apparent, underscoring the superiority of PSMA PET over conventional imaging — particularly in early-stage disease — and supporting its routine inclusion in future trials.
- Five-year metastasis-free survival favors apalutamide. Patients in the apalutamide arm achieved a meaningfully higher rate of five-year metastasis-free survival (78.2 percent vs. 73.5 percent), suggesting durable long-term benefit from perioperative ARI use in surgical candidates with high-risk disease. The authors suggested these results are broadly generalizable to this patient population.
Overall, the study authors found that patients in the perioperative apalutamide cohort had significantly longer event-free survival (57.1 months vs. 38.4 months) and an approximately 31-month median longer time before subsequent local or systemic therapy (74.2 months vs. 41.5 months) in comparison to the placebo group.
“Patients enrolled in our trial were evaluated in accordance with the latest evolving standards in diagnostics, and results are broadly generalizable to those with high-risk localized or locally advanced prostate cancer who are candidates for radical prostatectomy,” added Talin and colleagues.
(Editor’s note: For related content, see “Molecular Imaging in Focus: PSMA PET Radiotracers and Urinary Radioactivity: What Head-to-Head Prospective Multicenter Research Reveals,” “SNMMI: Over 80 Percent of Patients with Osseous Oligometastatic PCa are Upstaged with PSMA PET/CT” and “Early SPECT/CT Response After Pluvicto May Help Predict Survival in Patients with mCRPC.”)
In regard to study limitations, the authors acknowledged the lack of comparison for the combination of perioperative systemic therapy and radical prostatectomy versus radical prostatectomy and subsequent adjunctive or salvage therapy. The researchers also conceded the lack of baseline PET imaging.
