SNMMI 2023: BPH-Related False Positive of 68Ga-PSMA PET/CT in the Diagnosis of Prostate Cancer: The Achilles' Heel of Biopsy-free Radical Prostatectomy?

(UroToday.com) The 2023 SNMMI annual meeting included a prostate cancer session, featuring a presentation by Dr. Yongxiang Tang discussing BPH-related false positives of 68Ga-PSMA PET/CT in the diagnosis of prostate cancer. 68Ga-PSMA PET/CT has previously been proposed as a promising modality for a “biopsy-free” way to diagnose prostate cancer. However, PSMA expression in benign prostatic hyperplasia (BPH) tissue and tissue-related reactions are concerns.


Furthermore, inadequate specificity or positive predictive value of an imaging diagnosis strategy could become the Achilles’ Heel of biopsy-free prostate cancer diagnosis. This retrospective study presented by Dr. Tang and colleagues at the SNMMI 2023 annual meeting was conducted to investigate the BPH-related false positive rate of 68Ga-PSMA PET/CT in detecting prostate cancer and the influence of maximum standardized uptake value (SUVmax) on biopsy-free diagnosis of prostate cancer.

 Between April 2020 and January 2022, patients who received a 68Ga-PSMA PET/CT because of clinical suspicion of prostate cancer based on elevated PSA (>4 ng/ml) or an abnormal DRE and subsequently were confirmed to have BPH or prostate cancer by systematic biopsy and/or targeted biopsy were eligible for this study. The 68Ga-PSMA PET/CT fusion images were interpreted using a five-point Likert scale, whereby all cases with a PET score of 1 or 2 were classified as negative, while those with a PET score of 3, 4, or 5 were categorized as positive. For positive patients, the SUVmax value of the dominant lesion on PET was recorded for further analysis. Also, the highest SUVmax in the prostate gland was collected for negative cases with low-level radiotracer uptake. Prostate biopsy tissues were examined using immunohistochemistry staining to determine PSMA expression. As follows are representative 68Ga-PSMA PET/CT and immunohistochemistry images of each PET score:

PET images
The Spearman rank correlation analysis was performed to estimate the correlation between the SUVmax and ISUP grade group, and receiver operating characteristic curves were generated for SUVmax values, from which the area under the curve and the Youden index was calculated.

 In this study, there were 89 BPH patients and 94 prostate cancer patients. Overall, 27 of the 89 BPH cases were considered 68Ga-PSMA PET/CT-positive, and all dominant lesions were confirmed to be BPH tissue through targeted biopsy and were regarded as BPH-related false positives (30.3%). To explore the efficacy of SUVmax in discriminating positive BPH from prostate cancer and its influence on biopsy-free prostate cancer diagnosis, the SUVmax values between positive BPH and prostate cancer patients with different ISUP grade group were examined:

  • SUVmax value of ISUP grade group 1 patients was slightly higher compared with that of positive BPH, with no significant difference
  • SUVmax was weak in discriminating BPH from prostate cancer in all ISUP grade groups

SUVmax 

Considering that SUVmax positively correlated with ISUP grade group (rspearman = 0.4093, p = 0.0004), and ISUP grade group 2 patients had a higher SUVmax value than ISUP grade group 1 patients,

SUVmax 2

Dr. Tang and colleagues further evaluated the ability of SUVmax to discriminate clinically insignificant prostate cancer and positive BPH from clinically significant prostate cancer by adding positive BPH patients to ISUP grade group 1. Importantly, this analysis showed that the SUVmax value of ISUP grade group 2 was significantly higher than that of the mixed group, and preliminarily may indicate the potential of SUVmax in distinguishing clinically insignificant prostate cancer from BPH: 

SUVmax 3

In fact, SUVmax could effectively distinguish BPH and ISUP grade group 1 patients with an area under the curve of 0.8562, the optimal SUVmax cutoff value was 9.750, with a sensitivity of 64.7% and a specificity of 97.2%: 

specificity

Considering the importance of specificity in biopsy-free prostate cancer diagnosis, the optimal SUVmax cutoff value with 100% specificity was 14.6, with a sensitivity of 41.2% (95% CI 31.3% to 51.8%) and a specificity of 100% (95% CI 90.4% to 100%).

Dr. Tang concluded this presentation discussing BPH-related false positives of 68Ga-PSMA PET/CT in the diagnosis of prostate cancer, by highlighting that using SUVmax values in biopsy-free prostate cancer diagnosis can effectively exclude both BPH and ISUP grade group 1 patients.

Presenterd by: Yongxiang Tang, PhD, Xiangya Hospital, Xiangya Hospital

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting, Chicago, IL, Sat, June 24 – Tues, June 27, 2023.