PSMA targeted radiotracers detect biochemically recurrent prostate cancer at low PSA levels
Imaging of prostate specific membrane antigen (PSMA) targeted radiotracers appears to be useful in detecting biochemically recurrent prostate cancer at low prostate-specific antigen (PSA) levels, suggest the results of a systematic review and meta-analysis.
“However, existing studies are heterogeneous and limited by retrospective design, publication bias and limited reference standards,” researchers said.
Forty-three studies, which included 5,113 patients, met the inclusion criteria. Of these, 15 (34.8 percent) were prospective, three (6.9 percent) were multi-institutional and the remainder were conducted at a single centre. Eighteen studies (41.8 percent) were performed in patients after radical prostatectomy, two (4.6 percent) in patients after radiotherapy, and 23 (53.5 percent) in patients after radical prostatectomy and radiotherapy. [J Urol 2019;202:231-240]
Median age of participants was 68 years (interquartile range [IQR], 67–70), and median PSA was 1.6 ng/ml (IQR, 0.7–4.4). Thirty-three (76.7 percent) studies assessed Gallium-68 PSMA-11 (Ga-HBED-CC) positron emission tomography (PET)/computerized tomography (CT).
In the entire cohort, the pooled detection rate was 70.2 percent (95 percent CI, 65.0–75.4). The pooled detection rate for PSA <0.5, 0.5–0.9, 1–1.9 and ≥2 ng/ml was 44.9 percent (36.0–53.9), 61.3 percent (52.3–70.3), 78.2 percent (70.8–85.6) and 93.9 percent (92.0–95.8), respectively.
Furthermore, there was a positive reference standard in 684 of 715 patients (95.7 percent). Significant heterogeneity and publication biases were also present (p<0.01).
“PSMA targeted radiotracers have been shown to detect more and smaller lesions than non-PSMA PET radiotracers, CT and magnetic resonance imaging (MRI),” researchers said.
A study of 18F PSMA-1007 showed that 44 of 50 (88 percent) detected positive lymph nodes were <8 mm in the short axis, which is the subthreshold for established tumour response criteria on CT and MRI. [J Nucl Med 2018;59:632]
In another study, PSMA PET but not CT detected 65 of 168 bone metastases. There was a similar higher detection rate found for 68Ga PSMA-11 and 18F Na-F PET/CT compared to diffusion weighted imaging on MRI, according to researchers.
“Given these possible diagnostic advantages, the role of PSMA may extend beyond biochemical recurrence to the initial staging of high-risk prostate cancer and for treatment evaluation in metastatic cases,” they added.
The current study searched for articles in PubMed and Embase databases from 2012 to July 2018. Included in the analysis were studies evaluating men with prostate cancer biochemical recurrence after definitive therapy and without known metastatic disease who underwent PSMA PET/CT to detect recurrent disease.
Researchers used QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) to assess risk of bias and applicability concerns, as well as the Cochrane Q and an I2 estimate to evaluate statistical heterogeneity. The reference standard was pathology findings, follow-up imaging or a PSA decline after salvage treatment. A random effects model was used to calculate pooled estimates and 95 percent CIs around the prevalence of a positive examination in the study population.
“Multisite and single site, phase II/II, prospective single-arm. and comparative studies are underway to verify and validate [the findings of this study],” researchers noted.