When assessing the efficacy of androgen receptor-targeted agents (ARTAs) or chemotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC), new research reveals significant differences between prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) evaluation and prostate-specific antigen (PSA) response.
For the retrospective study, recently published in the European Journal of Radiology, researchers compared PSMA PET/CT with the imaging agent (18F)PSMA-1007 PET/CT (Pylarify, Lantheus) versus PSA response in 31 patients with mCRPC who were treated with ARTAs (enzalutamide or abiraterone) and 29 patients with mCRPC treated with chemotherapy (docetaxel or cabazitaxel).
When assessing treatment effectiveness, the researchers found discordant results between PSMA PET/CT and PSA response in 47 percent of the cohort. In 89 percent of these cases, PSMA PET/CT revealed worse treatment response, according to the study authors. Among patients who had greater than a 50 percent decrease in PSA levels after treatment, the study authors pointed out that 31 percent demonstrated progressive prostate cancer (PCa) on PSMA PET/CT scans.
The researchers also noted that PSMA PET/CT was a better predictor of overall survival (hazard ratio (HR) of 4.05) in comparison to PSA response (HR of 2.53) for patients in this cohort.
“These results suggest that the superior predictive ability of PSMA PET/CT is due to its ability to detect progressive disease earlier than PSA in a significant proportion of patients,” wrote study co-author Linda Heijmen, M.D., who is affiliated with the Department of Radiology in the Section of Nuclear Medicine at Leiden University Medical Center in Leiden, the Netherlands, and colleagues.
The study authors emphasized that the enhanced accuracy of PSMA PET/CT in reflecting the course of mCRPC after treatment has significant implications in the management of these patients.
Three Key Takeaways
1. Superior predictive ability of PSMA PET/CT. PSMA PET/CT demonstrated better accuracy in predicting treatment outcomes compared to PSA response in patients with metastatic castration-resistant prostate cancer (mCRPC). PSMA PET/CT detected progressive disease earlier than PSA in a significant number of patients.
2. High discordance between PSMA PET/CT and PSA response. The study found a 47 percent discordance rate between PSMA PET/CT evaluation and PSA response, with 89 percent of these cases showing worse outcomes on PSMA PET/CT despite PSA responses.
3. Implications for treatment decisions. The superior sensitivity of PSMA PET/CT allows for more accurate assessment of treatment efficacy, leading to earlier discontinuation of ineffective therapies, reducing toxicity and cost, and potentially improving patient survival by enabling timely initiation of effective treatments.
“The systematic use of PSMA PET/CT for treatment response evaluation can allow for earlier discontinuation of ineffective treatments, (minimizing) unnecessary toxicity and costs, and providing the opportunity to initiate potentially effective treatment earlier in these patients. It can also allow for continuation of treatment in those patients with the greatest survival benefit,” maintained Heijmen and colleagues.
Noting that this is the first study to evaluate the use of (18F)PSMA-1007 to assess mCRPC treatment, the researchers noted key advantages over 68Ga-labelled radiotracer agents in terms of a longer half-life and enhanced spatial resolution. They also cautioned about a higher risk of unspecific uptake in bone that can lead to false positives with (18F)PSMA-1007.
(Editor’s note: For related content, see “Phase 3 Study Shows Viability of 177Lu-PSMA-617 for Taxane-Naïve Metastatic Castration-Resistant Prostate Cancer,” “Combination Therapy with Enzalutamide Yields 31 Percent Improvement in Radiological Progression-Free Survival for mCRPC” and “Emerging PSMA Radioligand Therapy Shows Benefits for Metastatic Castration-Resistant Prostate Cancer.”)
In regard to study limitations, the authors noted the retrospective design and the small cohort of 60 patients. They also acknowledged the absence of diagnostic computed tomography or bone scans, and that patient enrollment was limited to patients with mCRPC who were treated with androgen receptor-targeted agents (ARTAs) and taxane-based chemotherapy.
