(UroToday.com) The 2024 PSMA conference featured a presentation by Dr. Robert Reiter discussing the clinical impact of PSMA PET prior to prostatectomy. The goals of imaging for localized disease are (i) to collect staging information, including the detection of metastatic disease, along with detection and characterization of primary tumor (multifocality, tumor size/extent, and extracapsular vs organ confined), and (ii) assess functional/biological information, related to prognosis and prediction.
Dr. Reiter first discussed the use of PSMA PETversus MRI for detection of prostate cancer. Based on work from Hope et al. we know that 18% of men with a negative PSMA CT have N1 disease after a radical prostatectomy + pelvic lymph node dissection.1 Moreover, the sensitivity for detection of lymph nodes is higher for nodes that are > 1 cm vs < 1 cm. A study from Dr. Reiter’s group assessing the detection of individual prostate cancer foci via mpMRI found that significant predictors of detection on univariable analysis included (i) larger size, (ii) higher Gleason score, (iii) index lesion status (iv) and solitary tumors:2
Raveenthiran and colleagues evaluated the ability of mpMRI and PSMA PET/CT individually and in combination, to predict tumor location and Gleason score ≥3+4 on robot prostatectomy histology in 1,123 men. With regard to index lesion sensitivity, this study found the following outcomes:3
- PSMA: 82%
- MRI: 80%
- Combined: 92%
- 10% only identified by PSMA PET/CT
- 8% only identified by MRI
Notably, there was a correlation of SUV with tumor grade (akin to the MRI PI-RADS score).
Work from Dr. Reiter’s group also suggests that both larger prostate cancer lesions and more aggressive prostate cancer lesions are more likely to be identified by imaging:
To discuss PSMA PET/CT as a predictor of clinical outcome, Dr. Reiter notes that in a study of 45 patients with a negative MRI or no MRI, PSMA PET was positive in 55.5% (25/45) of patients and prostate cancer was detected in 44% of patients (11/25).4 Of note in this study, SUV correlated with Gleason Group 2 or higher disease. Djaileb and colleagues recently published a follow-up analysis of a phase 3 imaging trial assessing presurgical 68Ga-PSMA-11 PET for biochemical risk assessment.5 The goal of this study was to assess the added prognostic value of presurgical PSMA-PET for BCR-FS compared with the presurgical CAPRA and postsurgical CAPRA-S scores in patients with intermediate- to high-risk prostate cancer treated with radical prostatectomy and pelvic lymph node dissection. As follows are the unadjusted Kaplan-Meier curves of (A) high PSMA prostate uptake, (B) PSMA extraprostatic disease (N1/M1), (C) CAPRA score, and (D) CAPRA-S score for BCR-FS:
Based on the above figure, preoperative PSMA N0/M0 vs N1M0 (B) is similar to post-operative CAPRA score for the prediction of biochemical recurrence (D).
Dr. Reiter then discussed PSMA as a biomarker for tumor biology and treatment response. It has previously been shown that in discovery and validation of molecular pathways associated with PSMA (FOLH1) from the TCGA database, that PSMA high expression is associated with metabolism, cell growth/division, and androgen response, whereas PSMA low expression is associated with inflammation, hypoxia, and EMT. PSMA is also highest in primary adenocarcinoma and lowest in neuroendocrine prostate cancer. Additionally, PSMA-low tumors are associated with shorter time to recurrence:
Finally, Dr. Reiter discussed radio-guided surgery for N1 disease by PSMA PET/CT. A study from Farolfi et al. suggest that failure to remove PSMA detected disease is common with “cognitive” salvage lymphadenectomy.6 Among 191 patients with PSA persistence after radical prostatectomy and undergoing a 68Ga-PSMA PET/CT, 33 patients also had a pre-surgical 68Ga-PSMA PET/CT, thus allowing the determination of PSMA persistence and recurrence. Among these 33 patients, 15 (45%) had a >=1 lesion identified before radical prostatectomy and after surgery:
Dr. Reiter has been a part of the RDRC Biodistribution Study Design, utilizing 99mTc-PSMA I&S radio-guided surgery:
To highlight this technology, Dr. Reiter then shared a case of a 45 year old male with a PSA of 80.7 who underwent a prostate biopsy that showed GG4 on the entire left side of the prostate, GG3 in the right mid apex and left base, as well as GG2 in the right base, right lateral base, with all cores showing 95% involvement. The patient’s prostate size was 42 g and Decipher score was 0.65. After his biopsy, a PSMA PET/CT showed SUVmax of 77 in the majority of the gland and right obturator node (0.7 cm in size), which was SUVmax 18. A subsequent MRI showed a PI-RADS 5 lesions in the right posterior lateral prostate with likely extracapsular extension, with no enlarged pelvic lymph nodes. As such, he started on Lupron and abiraterone as per the PROTEUS protocol and 6 months later a PSMA PET showed diffuse uptake in the prostate SUVmax of 37 (previously 77), and SUVmax in the right node of 8.7 (previously 18.2), with no uptake in the left nodes. Another MRI showed an 18 g prostate, and the entire posterior of the prostate occupied by tumor. The following shows this patient’s MRI and PSMA PET after hormonal therapy:
Following prostatectomy and probe guided detection of the right common iliac lymph node during pelvic lymph node dissection, the patient still has an undetectable PSA
Dr. Reiter concluded his presentation discussing the clinical impact of PSMA prior to prostatectomy with the following take-home points:
- PSMA PET can improve detection of cancer when added to MRI (and vice versa)
- PSMA PET is a predictor of biochemical recurrence and improves upon standard pre-op factors
- PSMA PET may provide important biological information to aid in treatment
- Radioguidance may improve resection of extra-prostatic disease
Presented by: Robert Reiter, MD, UCLA, Los Angeles, CA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 PSMA Conference, San Francisco, CA, Thurs, Jan 18 – Fri, Jan 19, 2024.
Related content: Clinical Impact of PSMA PET Prior to Prostatectomy “Presentation” - Robert Reiter
References:
- Hope TA, Eiber M, Armstrong WR, et al. Diagnostic Accuracy of 68Ga-PSMA-11 PET for Pelvic Nodal Metastasis Detection Prior to Radical Prostatectomy and Pelvic Lymph Node Dissection: A Multicenter Prospective Phase 3 Imaging Trial. JAMA Oncol. 2021 Nov 1;7(11):1635-1642.
- Johnson DC, Raman SS, Mirak SA, et al. Detection of individual prostate cancer foci via multiparametric magnetic resonance imaging. Eur Urol. 2019 May;75(5):712-720.
- Raveenthiran S, Yaxley WJ, Franklin T, et al. Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography and Multiparametric Magnetic Resonance Imaging Compared to Totally Embedded Radical Prostatectomy Histopathology: Implications for the Diagnosis and Management of Prostate Cancer. J Urol. 2022 Mar;207(3):573-580.
- Lopci E, Saita A, Lazzeri M, et al. 68Ga-PSMA Positron Emission Tomography/Computerized Tomography for Primary Diagnosis of Prostate Cancer in Men with Contraindications to or Negative Multiparametric Magnetic Resonance Imaging: A Prospective Observational Study. J Urol. 2018 Jul;200(1):95-103.
- Djaileb L, Armstrong WR, Thompson D, et al. Presurgical 68Ga-PSMA-11 Positron Emission Tomography for Biochemical Recurrence Risk Assessment: A Follow-up Analysis of a Multicenter Prospective Phase 3 Imaging Trial. Eur Urol. 2023 Dec;84(6):588-596.
- Farolfi A, Gafita A, Calais J, et al. 68Ga-PSMA-11 Positron Emission Tomography Detects Residual Prostate Cancer after Prostatectomy in a Multicenter Retrospective Study. J Urol. 2019 Dec;202(6):1174-1181.