(UroToday.com) The 2023 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between June 2nd and June 6th was host to a prostate, testicular, and penile cancers poster discussion session. In the Discussant portion of this session, Dr. Louise Emmett discussed the current and future states of novel imaging modalities for advanced prostate cancer, highlighting three abstracts from this session:
- Do bone scans over-stage disease compared to PSMA PET? An international multicenter retrospective study with blinded independent readers
- PSMA PET guided salvage radiotherapy among prostate cancer patients in the post-prostatectomy setting: a single center post-hoc analysis
- Prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET) disease extent and overall survival (OS) in patients (pts) with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC): An international multicenter retrospective study
Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that acts as a glutamate carboxypeptidase and has a pro-proliferative function, activating Pi3k and Akt/mTOR pathways via glutamate cleavage. High cellular PSMA expression has been associated with worse oncologic outcomes, including increased rates of castrate resistance development.
Dr. Emmett first discussed the abstract titled: “Do bone scans over-stage disease compared to PSMA PET? An international multicenter retrospective study with blinded independent readers”. This was a retrospective analysis of 167 prostate cancer patients who underwent both a bone scan and PSMA-PET within 100 days at three centers (UCSF, UCLA, University Hospital Essen). Patients did not receive any new interval therapy in the period between the two imaging modalities being performed, and patients were included across the disease spectrum (initial diagnosis, biochemical recurrence, castrate sensitive or resistant prostate cancer). Each study was independently read by three blinded readers, and the results of the PSMA-PET served as the reference standard.
17% of patients were staged as M1b on PSMA PET, whereas 30% of patients were staged as such on bone scan. This study demonstrated that the positive predictive value (PPV) of bone scan in the overall cohort was 73%; however, this decreased to 43% in patients undergoing a bone scan in the initial staging setting, meaning that 57% of patients with evidence of bone metastases on bone scans had false positive lesions, when compared to PSMA PET as reference standard. These results are consistent with those observed in the proPSMA study where the false positive rates of CT/bone scan were 23%, compared to 7% with 68Ga-PSMA PET.1
Dr. Emmett next discussed the second abstract:” PSMA PET guided salvage radiotherapy among prostate cancer patients in the post-prostatectomy setting: a single center post-hoc analysis”. This was a post-hoc analysis of five prospective studies of PSMA-PET/CT conducted at UCLA between 2016 and 2021. Patients were inclusion eligible if they:
- Had biochemical recurrence post-radical prostatectomy
- Initiated salvage radiotherapy within 3 months of PSMA-PET/CT
- Did not receive salvage radiotherapy with palliative intent
- Had at least 12 months of follow-up following completion of salvage radiotherapy
- Had treatment details available
- Did not have distant metastases by conventional imaging on upfront staging
Dr. Emmett highlighted that this was a particularly “high risk” group of biochemically relapsed patients, with 33% having received prior salvage radiotherapy. Median PSA was 0.62 ng/ml (range: 0.06 – 35) and median follow-up was 32 months (12 – 70). 41% of patients in this cohort had a negative PSMA PET, with the remaining 59% having PSMA PET positive disease as follows:
- Local only: 17%
- Pelvic nodal: 21%
- M1 disease: 28%
This “high risk” nature of the cohort is highlighted by the steep PFS curves demonstrated below. As expected, patients with PET-detected M1 disease had significantly worse outcomes.
How do these results compare to those from the existing literature? A similar analysis of patients with biochemical recurrence post-radical prostatectomy similarly demonstrated that approximately 50% of patients in this setting have a negative scan or fossa-limited disease. Similarly, patients with evidence of negative PSMA findings or fossa-limited disease fare significantly better compared to those with PSMA-detected distant metastases.2 Dr. Emmett noted that we await the results of the PSMA-SRT trial, a phase III randomized multicenter trial of 68Ga-PSMA-11 PET/CT for prostate cancer salvage radiotherapy planning.
Dr. Emmett next discussed the third abstract: “Prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET) disease extent and overall survival (OS) in patients (pts) with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC): An international multicenter retrospective study”.
The study included 200 patients with nmCRPC patients from five centers and with disease characteristics similar to those observed in the SPARTAN, PROSPER, and ARAMIS trials:
- PSA doubling time ≤10 months and/or Grade Group 4 or 5 disease
- No pelvic nodes ≥2 cm in the short axis
- No evidence of distant metastases on conventional imaging
All patients underwent a PSMA-PET/CT, all evaluated by three independent readers. A previous report of this cohort had demonstrated that 98% of these patients had PSMA positive disease (55% with M1 disease and 44% with pelvic-confined disease), with a PPV of 97%.3
At a median follow-up of 74 months, 28% of patients had died and median OS was 74 months. Patients with evidence of polymetastatic disease (5+ lesions) had significantly worse OS (median 61 versus not reached, p=0.024) and new metastases-free survival rates (38 versus 60 months, p=0.018).
Furthermore, the investigators demonstrated that PSMA intensity was predictive of OS. Patients with an SUVmax of ≥8.4 had significantly worse OS (63 months versus not reached, p=0.035).
These findings mirror those form the PRIMARY study that demonstrated that higher SUVmax was associated with worsening ISUP grade group.
Dr. Emmett concluded that:
- PSMA PET is an imaging biomarker that will be the new gold standard for prostate cancer, with no role for bone scans
- PSMA PET is effective at triaging those patients requiring more intense systemic treatments at biochemical recurrence
- nmCRPC is a multi-faceted entity in the era of PSMA PET
- We need to create knowledge bridges between technologies by embedding PSMA PET into prospective therapy trials in biochemical recurrence, mHSPC, nmCRPC, and mCRPC
Presented by: Louise Emmett, MBChB, FRACP, Professor, UNSW Director of Theranostics and Nuclear medicine, St Vincent's Hospital, Sydney, New South Wales, Australia
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.References:
1. Hofman MS, Lawrentschuk N, Francis, RJ, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): A prospective, randomized, multicentre study. Lancet 2020;395(10231):1208-1216.
2. Emmett L, Tang R, Nandurkar R, et al. 3-Year Freedom from Progression After 68Ga-PSMA PET/CT-Triaged Management in Men with Biochemical Recurrence After Radical Prostatectomy: Results of a Prospective Multicenter Trial. J Nucl Med 2020;61(6):866-872.
3. Fendler WP, et al. Prostate-Specific Membrane Antigen Ligand Positron Emission Tomography in Men with Nonmetastatic Castration-Resistant Prostate Cancer. Clin Cancer Res 2019;25(24):7448-54.
ASCO 2023: Do Bone Scans Over-Stage Disease Compared to PSMA PET? An International Multicenter Retrospective Study with Blinded Independent Readers
ASCO 2023: PSMA PET Guided Salvage Radiotherapy Among Patients with Prostate Cancer in the Post-Prostatectomy Setting: A Single Center Post-Hoc Analysis
ASCO 2023: PSMA Ligand Positron Emission Tomography Disease Extent and Overall Survival in Patients with High-Risk Nonmetastatic Castration-Resistant Prostate Cancer: An International Multicenter Retrospective Study