What’s behind 68Ga-PSMA-11 uptake in primary prostate cancer PET? Investigation of histopathological parameters and immunohistochemical PSMA expression patterns

Rüschoff, Jan H.; Ferraro, Daniela A.; Muehlematter, Urs J.; Laudicella, Riccardo; Hermanns, Thomas; Rodewald, Ann‐Katrin; Moch, Holger; Eberli, Daniel; Burger, Irene A.; Rupp, Niels J.

doi:10.1007/s00259-021-05501-1

Cited by 62 publications

(59 citation statements)

References 29 publications

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“…Guidelines recommend that for low- and intermediate-risk PCa patients, a biopsy may be more appropriate than using mpMRI alone (this depends on other factors, such as high PSA, family history, and age) [ 17 , 33 ]. Our study showed that an additional 68 Ga-PSMA PET/CT could be helpful for deciding if these low- and intermediate-risk PCa patients should undergo a prostate biopsy or further management [ 34 ]. Another key finding was that low- and intermediate-risk PCa patients with a PSA ≥ 9.4 ng/ml and age ≥ 62.5 years were more likely to have a positive 68 Ga-PSMA PET/CT result.…”

Section: Discussionmentioning

confidence: 99%

Comparison of 68Ga-PSMA PET/CT and multiparametric MRI for the detection of low- and intermediate-risk prostate cancer

et al. 2022

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Purpose To assess 68Ga-PSMA PET/CT for detection of low- and intermediate-risk prostate cancer (PCa), high-risk PCa in comparison with mpMRI, respectively, and to determine which of low- and intermediate-risk PCa are more likely to be detected by 68Ga-PSMA PET/CT. Methods We conducted a retrospective analysis of patients who had undergone a prostate biopsy and/or radical prostatectomy and who were scanned with 68Ga-PSMA PET/CT and mpMRI between June 2019 and March 2021. The mpMRI images were scored with the Prostate Imaging-Reporting and Data System Version 2.1 (PI-RADS) and were classified as either negative (PI-RADS 1–3) or positive (PI-RADS 4–5). Suspicious 68Ga-PSMA PET/CT lesions were reviewed for each relevant patient and classified by double-trained board-certified nuclear medicine physicians. The results were evaluated with the histopathological outcome. All patients were classified according to the D’Amico classification, and the clinical data were combined for stratified analysis. Result A total of 101 patients who were pathologically diagnosed with PCa were analyzed. Of the 101 patients, 88 (80.6%) patients presented with a pathologic mpMRI, and 85 (79.1%) with a pathologic 68Ga-PSMA PET/CT. In the high-risk PCa cohort, 68Ga-PSMA PET/CT was positive in 64/66 (97.0%) patients and yielded a higher detection rate than that for the mpMRI patients (58/66, 87.9%; p < 0.05). However, mpMRI provided superior diagnostic confidence in identifying low- and intermediate-risk PCa (30/35, 85.7% vs. 21/35, 60.0%; p < 0.05). When the age threshold exceeded 62.5 years and the serum prostate specific antigen (PSA) threshold exceeded 9.4 ng/ml, a higher uptake of PSMA was more likely to occur in the lesions of low- and intermediate-risk PCa. Conclusion The diagnostic performance of 68Ga-PSMA PET/CT was superior to that of mpMRI in the high-risk PCa cohort, which was consistent with prior studies. Furthermore, in the initial diagnosis of low- and intermediate-risk PCa, we found that mpMRI showed a higher diagnostic accuracy than 68Ga-PSMA PET/CT did. Low- and intermediate-risk PCa patients with a PSA ≥ 9.4 ng/ml and age ≥ 62.5 years were more likely to have a positive 68Ga-PSMA PET/CT result.

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Section: Discussionmentioning

confidence: 99%

Comparison of 68Ga-PSMA PET/CT and multiparametric MRI for the detection of low- and intermediate-risk prostate cancer

et al. 2022

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“…A wide range of cutoffs was proposed to detect significant prostate cancer, ranging from the SUVmax 3.15 to up to the SUVmax 9.1 [ 9 , 10 , 11 , 12 ]. In the current work, we applied the SUVmax of 6.6 cutoff, as previously described by Uprimny et al [ 8 ].…”

Section: Resultsmentioning

confidence: 99%

Very Low Prostate PET/CT PSMA Uptake May Be Misleading in Staging Radical Prostatectomy Candidates

Rosenzweig

Haramaty

Davidson

et al. 2022

JPM

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Purpose: to evaluate a unique subpopulation of radical prostatectomy (RP) candidates with “negative” prostate 68Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computed tomography (CT) imaging scans and to characterize the clinical implications of misleading findings. Materials and Methods: This case-control retrospective study compared the final histological outcomes of patients with “negative” pre-RP PSMA PET/CT prostate scans (with a prostate maximal standardized uptake value [SUVmax] below the physiologic uptake) to those with an “intense” prostatic tracer uptake (with a SUVmax above the physiologic uptake). The patients underwent an RP between March 2015 and July 2019 in five academic centers. Data on the demographics, comorbidities, prostate-specific antigen (PSA) and rectal exam findings, prior biopsies, imaging results, biopsies, and RP histology results were collected. Results: Ninety-seven of the 392 patients who underwent an RP had PSMA PET/CT imaging preoperatively. Fifty-two (54%) had a “negative” uptake (in the study group), and 45 (46%) had a “positive” uptake (in the control group). Only the lesion size and SUVmax values on the PSMA PET/CT differed between the groups preoperatively. On the histological analysis, only the ISUP score, seminal vesicles invasion, T stage, and positive margin rates differed between the groups (p < 0.05), while 50 (96%) study group patients harbored clinically significant disease (ISUP ≥ 2), with an extra-prostatic disease in 24 (46%), perineural invasion in 35 (67%), and positive lymph nodes in 4 (8%). Conclusions: Disease aggressiveness generally correlated with an intense PSMA uptake on the preoperative PSMA PET/CT, but a subpopulation of patients with clinically significant cancer and aggressive characteristics showed a deceptively weak PSMA uptake. These data raise a concern about the unqualified application of PSMA PET/CT for staging RP candidates.

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“…The presence of focal uptake on PSMA-PET/CT, the standardised uptake value (SUVmax) and the maximal dimensions of PET-avid lesions have been correlated with the presence of csPCa [ 20 , 21 ]. There is a range of proposed cutoffs to detect csPCa from SUVmax 3.15 to up SUVmax 9.1 [ 22 , 23 ]; the concordance between preoperative PSMA PET/TC evaluation (SUVmax, dimension of the lesion), and definitive prostate specimen ranges from 81.2% (24) to 96% [ 24 , 25 , 26 , 27 , 28 ]. Moreover, PSMA PET/MRI seems to reduce the false positive rate of PET/CT (about 8% of cases) [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Could 68Ga-PSMA PET/CT Evaluation Reduce the Number of Scheduled Prostate Biopsies in Men Enrolled in Active Surveillance Protocols?

Pepe

Roscigno

Pepe

et al. 2022

JCM

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Background: To evaluate the accuracy of 68Ga-prostate specific membrane antigen (PSMA) PET/CT in the diagnosis of clinically significant prostate cancer (csPCa) (Grade Group > 2) in men enrolled in Active Surveillance (AS) protocol. Methods: From May 2013 to May 2021, 173 men with very low-risk PCa were enrolled in an AS protocol study. During the follow-up, 38/173 (22%) men were upgraded and 8/173 (4.6%) decided to leave the AS protocol. After four years from confirmatory biopsy (range: 48–52 months), 30/127 (23.6%) consecutive patients were submitted to mpMRI and 68Ga-PSMA PET/CT scan before scheduled repeated biopsy. All the mpMRI (PI-RADS > 3) and 68Ga-PET/TC standardised uptake value (SUVmax) > 5 g/mL index lesions underwent targeted cores (mpMRI-TPBx and PSMA-TPBx) combined with transperineal saturation prostate biopsy (SPBx: median 20 cores). Results: mpMRI and 68Ga-PSMA PET/CT showed 14/30 (46.6%) and 6/30 (20%) lesions suspicious for PCa. In 2/30 (6.6%) men, a csPCa was found; 68Ga-PSMA-TPBx vs. mpMRI-TPBx vs. SPBx diagnosed 1/2 (50%) vs. 1/2 (50%) vs. 2/2 (100%) csPCa, respectively. In detail, mpMRI and 68Ga-PSMA PET/TC demonstrated 13/30 (43.3%) vs. 5/30 (16.7%) false positive and 1 (50%) vs. 1 (50%) false negative results. Conclusion: 68Ga-PSMA PET/CT did not improve the detection for csPCa of SPBx but would have spared 24/30 (80%) scheduled biopsies showing a lower false positive rate in comparison with mpMRI (20% vs. 43.3%) and a negative predictive value of 85.7% vs. 57.1%, respectively.

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What’s behind 68Ga-PSMA-11 uptake in primary prostate cancer PET? Investigation of histopathological parameters and immunohistochemical PSMA expression patterns

Cited by 62 publications

References 29 publications

Comparison of 68Ga-PSMA PET/CT and multiparametric MRI for the detection of low- and intermediate-risk prostate cancer

Comparison of 68Ga-PSMA PET/CT and multiparametric MRI for the detection of low- and intermediate-risk prostate cancer

Very Low Prostate PET/CT PSMA Uptake May Be Misleading in Staging Radical Prostatectomy Candidates

Could 68Ga-PSMA PET/CT Evaluation Reduce the Number of Scheduled Prostate Biopsies in Men Enrolled in Active Surveillance Protocols?

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