What is the Optimal PET/CT Approach for Assessing Recurrence of Prostate Cancer?

A comparison of PET/CT scan tracers found that prostate-specific membrane antigen (PSMA) performed better than ¹⁸F-fluciclovine with regard to the localization of biochemical recurrence of prostate cancer following radical prostatectomy, according to the results of the study published online ahead of print on July 30 in Lancet Oncology. The PSMA tracer is the preferred option, though experts say there is still room for improvement.

“Treatment of patients with biochemical recurrence of prostate cancer is guided by disease location and extent,” wrote study authors led by Jeremie Calais, MD, of the University of California, Los Angeles.

PET/CT scans can localize biochemical recurrence with higher detection rates and sensitivity than conventional imaging such as CT, bone scans, and MRI, but ¹⁸F-fluciclovine and PSMA with ⁶⁸Ga-PSMA-11 had not previously been directly compared. National Comprehensive Cancer Network (NCCN) guidelines recommend ¹⁸F-fluciclovine, while the European Association of Urology guidelines recommend PSMA PET/CT.

The new study included a total of 50 men with prostate cancer biochemical recurrence after radical prostatectomy and prostate-specific antigen levels ranging from 0.2 to 2.0 ng/mL. All patients underwent PET/CT scans using both tracers, with a median time between scans of 6 days. They were followed for a median of 8 months.

Detection rates of biochemical recurrence were significantly lower with ¹⁸F-fluciclovine, at 13 of 50 patients (26%), than with PSMA, at 28 of 50 patients (56%). This yielded an odds ratio of 4.8 (95% CI, 1.6–19.2; P = 0.0026). Post-hoc analyses confirmed the finding when including only those patients whose scans were conducted at the same institutions and only those done with contrast-enhanced CT.

The rates of detection with ¹⁸F-fluciclovine were significantly lower specifically in the pelvic lymph nodes region (8% vs 30%), with an OR of 12.0 (95% CI, 1.8–513.0; P = 0.0034), and for any extrapelvic lesions. No differences between the tracers were seen for individual extrapelvic lesion locations, or for prostate bed recurrence.

“PSMA PET/CT detects biochemical recurrence sites at low prostate-specific antigen 

 (PSA) concentrations more frequently and with higher reader agreement than ¹⁸F-fluciclovine PET-CT,” the authors concluded. “the results of this prospective head-to-head comparison indicate that PSMA should be the PET tracer of choice when PET/CT imaging is considered for subsequent treatment management decisions in patients with biochemical recurrence and low PSA concentrations.”

In an accompanying editorial, authors led by Nicola Fossati, MD, of IRCCS Ospedale San Raffaele in Milan, Italy, noted that the effect of the findings from the PET/CT scans on subsequent treatment decisions remain unknown.

“Future comparative trials addressing therapeutic rather than diagnostic outcomes are needed to assess the real clinical effect of novel PET/CT tracers,” they wrote.

Fossati and his co-authors also pointed out that the use of PSMA might still result in an underestimation, and thus potentially undertreatment, of recurrent prostate cancer.

“The introduction of ⁶⁸Ga-PSMA has improved the diagnostic accuracy of the PET/CT scan, but several issues still persist,” they wrote. “Novel tracers and future clinical trials are needed to improve performance.”