JU INSIGHT BPH-Related False-Positive of PSMA-PET in the Diagnosis of Prostate Cancer: The Achilles’ Heel of Biopsy-Free Radical Prostatectomy?

By: Wei Tang, MD, Xiangya Hospital, Central South University, Changsha, China; Yongxiang Tang, MD, PhD, Xiangya Hospital, Central South University, Changsha, China; Lin Qi, MD, PhD, Xiangya Hospital, Central South University, Changsha, China; Ye Zhang, MD, PhD, NHC Key Laboratory of Cancer Proteomics, Xiangya Hospital, Central South University, Changsha, China; Guyu Tang, MD, Xiangya Hospital, Central South University, Changsha, China; Xiaomei Gao, MD, PhD, Xiangya Hospital, Central South University, Changsha, China; Shuo Hu, MD, PhD, Xiangya Hospital, Central South University, Changsha, China; Yi Cai, MD, PhD, Xiangya Hospital, Central South University, Changsha, China | Posted on: 15 Dec 2023

Tang W, Tang Y, Qi L, et al. Benign prostatic hyperplasia-related false-positive of prostate-specific membrane antigen-positron emission tomography in the diagnosis of prostate cancer: the Achilles’ heel of biopsy-free radical prostatectomy?. J Urol. 2023;101097JU0000000000003680.

Study Need and Importance

Since the introduction of prostate biopsy, histopathological diagnosis through biopsy has been the gold standard for prostate cancer (PCa) diagnosis. Additionally, the execution of radical prostatectomy (RP) typically relies on prior biopsy pathology results. Advances in diagnostic techniques, such as prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) and multiparametric (mp) MRI, raise the question of whether RP can rely solely on imaging. In 2022, researchers from Technical University of Munich explored biopsy-free RP feasibility based on PSMA-PET and mpMRI in a 25-case study. However, there remains uncertainty about the true specificity of PSMA-PET. False-positives in PSMA-PET (where the results suggest PCa but biopsy indicates BPH) could potentially pose challenges in the path toward biopsy-free RP. Moreover, there is a lack of higher-level evidence-based research exploring the application of mpMRI and maximum standardized uptake value (SUVmax) in biopsy-free RP.

What We Found

The positivity rate of PSMA-PET in a population diagnosed with BPH using prostate histopathological examination as the gold standard is 30% (Figure). SUVmax effectively distinguishes PSMA-PET-positive BPH patients and clinically insignificant PCa, with an area under the curve value of 0.86. The optimal SUVmax cutoff value at 100% specificity is 15, resulting in a sensitivity of 41%. When utilizing strict diagnostic criteria combining PSMA-PET and mpMRI, the sensitivity for diagnosing clinically significant PCa is 49%, with a specificity of 100%.

Figure. Representative prostate-specific membrane antigen positron emission tomography (PET)/computed tomography (CT) and immunohistochemistry (IHC) images of each PET score. A, PET score 1: nearly no radiotracer uptake was presented in the prostate gland and it was considered benign; corresponding IHC analysis of the biopsy tissue also indicated a negative result. B, PET score 2: mild and diffuse radiotracer uptake pattern was observed but no focal lesions, prostate-specific membrane antigen–PET was interpreted as negative. IHC analysis of corresponding biopsy tissue showed a faint staining of prostate epithelial cells. C, PET score 3: low level and relatively focal radiotracer uptake pattern was observed. IHC analysis demonstrated a low-level expression of the prostate-specific membrane antigen. D, PET score 4: moderate and focal uptake pattern of prostate-specific membrane antigen inhibitor was observed and considered likely cancer; IHC also indicated moderate staining. E, PET score 5: relatively high and focal radiotracer uptake was seen in the images and considered cancerous; subsequent IHC staining demonstrated strong expression of the prostate-specific membrane antigen.

Limitations

The generalization of the findings of this study is limited by its retrospective research design and a relatively small sample size. Additionally, the diagnostic gold standard employed in this study still carries the potential for false-negatives.

Interpretation for Patient Care

For suspected PCa patients, a subset with imaging indications strongly suggestive of PCa might be eligible to bypass the biopsy step and proceed directly to RP. The remaining cases would still undergo traditional prostate biopsy to establish a definitive diagnosis.