Diagnostic Imaging Not Yet Enough for Biopsy-Free Radical Prostatectomy

While prostate-specific membrane antigen (PSMA)-PET may improve diagnostic accuracy in suspected prostate cancer, it may not be accurate enough to skip the biopsy when considering radical prostatectomy.

In a retrospective review of 89 men with benign prostatic hyperplasia (BPH), PSMA-PET prior to biopsy had a false-positive rate of 30%, with subsequent needle biopsy revealing negative findings in 27 of 64 patients considered PSMA-PET-positive, reported Yi Cai, MD, of Xiangya Hospital, Central South University in Hunan Province, China, and co-authors.

However, study findings did support earlier evidence for the efficacy of adding multi-parametric MRI (mpMRI) to PSMA-PET to exclude false-positive results, with the calculation of maximum standardized uptake value (SUVmax) making it possible to differentiate clinically significant prostate cancer from BPH and International Society of Urological Pathology Grade Group 1 patients with an area under the curve of 0.86, the authors noted in the Journal of Urology.

“Biopsy-free radical prostatectomy is still in its infant stage and its application must be approached with great caution,” they wrote, warning that a diagnostic imaging strategy with inadequate specific or positive predictive value could potentially become “the Achilles heel of biopsy-free radical prostatectomy.”

Transrectal or perineal prostate puncture biopsy remains the gold standard for prostate cancer diagnosis, with radical prostatectomy typically performed after histopathological confirmation of disease. However, some studies have indicated that PSMA-PET with mpMRI could allow patients to skip biopsy and proceed directly to radical prostatectomy.

The positive expression of PSMA in BPH tissue, as determined by immunohistochemistry assay, can reduce the specificity of PSMA-PET imaging diagnosis, Cai and team noted. “Currently, the positive criteria of PSMA-PET and mpMRI are generally considered suitable for the diagnosis of [clinically significant prostate cancer], and related studies have indicated the high sensitivity and specificity,” they wrote. “However, this standard may not be appropriate for biopsy-free radical prostatectomy due to false-positives.”

The sensitivity and specificity of stringent PET score and mpMRI Prostate Imaging Reporting & Data System (PI-RADS) criteria (both ≥4) in diagnosing clinically significant prostate cancer were 49% and 100%, respectively. The optimal SUVmax cutoff value, with 100% specificity suitable for radical prostatectomy, was 15, resulting in a sensitivity of 41%. “Specificity is a more essential measure for biopsy-free radical prostatectomy than overall diagnostic effectiveness and sensitivity,” the authors wrote.

The diagnostic efficacy of stringent PET score and PI-RADS for clinically significant prostate cancer suggests this is a feasible standard for biopsy-free radical prostatectomy, they concluded. Patients with imaging indications strongly suggestive of prostate cancer “might be eligible to bypass the biopsy step and proceed directly to [radical prostatectomy]. The remaining cases would still undergo traditional prostate biopsy to establish a definitive diagnosis.”

In an editorial comment accompanying the article, Brittney H. Cotta, MD, of the University of Texas MD Anderson Cancer Center in Houston, noted that even when PSMA-PET and mpMRI lesion scores were combined, 13% of study participants still had BPH-related false-positive results. Only high lesion scores of ≥4 for both PET and mpMRI PI-RADS could exclude BPH and low-grade prostate cancer with a specificity of 100%.

“The goal of biopsy-free radical prostatectomy remains undefined and is not standard of care,” Cotta emphasized. “This study validates the concern of BPH-related false-positives of PSMA-PET, even when combined with mpMRI. Certainly, it appears that neither imaging technology nor physician appetites are ready for biopsy-free radical prostatectomy.”

In a second editorial comment, Benjamin H. Baker, MD, and Jonathan H. Berger, MD, of the Naval Medical Center San Diego, agreed and pointed to recently reported findings showing that the frequency of prostate hyperplasia was higher in high versus low PI-RADS lesions. Taken together with the intrinsic rise of serum prostate-specific antigen (PSA) levels, “patients living with BPH may pose a challenge to ruling prostate cancer in (or out) without a tissue biopsy,” they wrote.

“Although this novel manuscript (and prior related publications) certainly does not yet get us to a stage where prostate cancer can be routinely treated (or ruled out) without a tissue biopsy,” Baker and Berger added, “there is mounting evidence to perhaps support future prospective studies (with particular benefit to those patients at higher risk of complications related to a prostate biopsy).”

In a published response, Cai and colleagues noted that “the notion of biopsy-free approaches for prostate cancer appears to have reached a stage where it can be proposed and discussed.” The evidence to date comes from retrospective studies with relatively low levels of evidence, they pointed out, adding that “we look forward to discovering the right things and making the right choices, even if the answer is negative.”

This observational study was conducted at Xiangya Hospital, with patients enrolled from April 2020 to January 2022. They underwent PSMA-PET due to clinical suspicion of prostate cancer based on elevated PSA (>4 ng/mL) or abnormal digital rectal examination and subsequently were confirmed to have BPH or prostate cancer by systematic biopsy or mpMRI-targeted or PSMA-PET-targeted biopsy. Median age at biopsy or surgery was 64-67 between the two groups.

Since the study used systematic biopsy combined with PSMA-PET- and mpMRI-targeted biopsy results as the gold standard for true negatives, the possibility of false-negative biopsy results cannot be ruled out, the study authors noted. “Therefore, the results of this study, as well as the feasibility of biopsy-free radical prostatectomy, still require further validation through more high-quality prospective studies.”

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