Randomized Controlled Trial of PSMA PET/CT Guided Intensification of Radiotherapy for Prostate Cancer: Detection Rates and Impact on Radiotherapeutic Management

Abstract

Secondary endpoints were overall survival, metastasis-free survival, incidence of acute and late toxicities, and quality of life (QOL). Stratification factors were Gleason score, pT stage, and center. We present the acute and late toxicity (CTCAE V3.0) and QOL (EORTC QLQ-C30 and PR-25 scales) results. Results: Between 2008 and 2016, 424 patients were randomized (n Z 212 aRT; n Z 212 sRT) in 46 centers, in France. The Independent Data Monitoring Board recommended that enrolment be stopped early due to insufficient accrual and low event rate. Median age was 63.8 years, with 77.3% of patients pT3a and 80.4% with Gleason 7. The baseline characteristics were similar in the arms. In the sRT arm, 113 patients (53.3%) had their biochemical relapse triggering sRT. The median delay between randomization and sRT was 23 months. Median follow-up was 6.3 years. Grade >2 acute toxicity was observed in 1.9% of patients in the sRT arm compared to 2.9% in the aRT arm (p Z 0.75). Late grade >2 toxicities, essentially incontinence, pollakiuria, sexual dysfunction, and hot flushes, were observed in 17/212 patients (8%) in the sRT arm, and in 42/212 (19.8%) in the aRT arm (p<0.001). The global health status measured by QLQC30 was not significantly different in the arms (p Z 0.114). Conclusion: Initial results from GETUG-AFU 17 show that aRT significantly increased the risk of late toxicity. No difference was seen in the QOL between arms. Further follow-up is needed to analyze long-term efficacy endpoints.

A Review on the Current Treatment Paradigm in High-Risk Prostate Cancer

“…In 75% of the cases, the sites of intensification were located outside of the initial planned radiotherapy fields. Findings of this study have encouraged the authors to evaluate this hypothesis in a randomized phase III trial [22]. Similar trials are underway assessing mpMRI-guided boosts using hypofractionation and ablative radiotherapy.…”

“…Acknowledging the limitation of a short follow-up duration, the authors did not find any benefit with respect to prostate cancer-specific survival (HR: 0.69, 95% CI: 0.27-1.79) or overall survival (HR: 1.26, 95% CI: 0.83-1.92). There are also studies that used PET to intensify radiotherapy to visible tumor [22] and others involving the use of stereotactic body radiotherapy (SBRT) and hypofractionation [23]. This treatment approach still needs further validation but may help to safely improve local tumor control.…”

“…The use of 18 F-fluciclovine-PET/CT led to a significant improvement in 3-year event-free survival (3-year event-free survival of 75.5% vs. 63%; HR for conventional imaging group: 2.05, 95% CI: 1.06-3.93) [73]. Menard et al conducted a phase II randomized controlled trial using PSMA PET/CT to intensify RT, with an objective of improving failure-free survival outcome [22]. A total of 136 patients with either high-risk prostate cancer or biochemical failure after radical prostatectomy were enrolled.…”

Piflufolastat F 18: Diagnostic First Approval

“…New lesions leading to radiotherapy intensification were detected with piflufolastat F 18 PET/CT in 46% of patients with high-risk prostate cancer (n = 60) and 45% of those with biochemical recurrence after radical prostatectomy (n = 76) in a randomized, controlled phase 2 trial (NCT03525288; n = 136) investigating whether intensification of radiotherapy based on PSMA PET/CT could improve failure-free outcomes [40]. In post-surgical patients (but not post-radiation patients), piflufolastat F 18 PET/CT correlated with PSA levels, PSA doubling time and PSA velocity a trial in 90 patients with biochemically recurrent prostate cancer after primary local therapy (NCT03181867) [27].…”