(UroToday.com) The first prostate cancer session at the 2021 European Association of Urology (EAU) Section of Oncological Urology (ESOU) Virtual Annual Meeting featured a number of case presentations focused on diagnosis and staging. The second of these, featuring a case presentation from Dr. Sandro Gaspar and a pro/con debate from Drs. Francesco Ceci and Henk van der Poel, examined the value of prostate-specific membrane antigen (PSMA) PET/CT compared to conventional imaging for the primary staging of patients with high-risk prostate cancer.
Dr. Gaspar began by providing the case presentation, introducing a 56-year-old man with good performance status referred for an elevated prostate-specific antigen (PSA). His past medical history was notable for excess weight with medically managed benign prostatic hyperplasia (BPH) and hypertension, and COVID-19 in April 2020. He is married with two children. With his medically managed BPH, his international prostate symptom score (IPSS) is 2. Digital rectal examination was normal. PSA performed in September 2020 was 9 ng/mL (free/total ratio 14%) and repeat performed December 2020 was 22 ng/mL. Based on nomograms, he has a high risk of both any prostate cancer (75%) and high-grade prostate cancer (>50%).
He then underwent 3-tesla mpMRI which demonstrated a 50cc gland, a PSA density of 0.42, a prostate imaging-reporting and data system (PIRADS) 5 lesion at the left base, and a suspicious lymph node (measuring 8mm) in the left obturator fossa. On the basis of these results, the patient underwent MRI-targeted and systematic biopsy demonstrated International Society of Urological Pathology (ISUP) grade group 4 disease in 13 of 23 cores bilaterally, with predominance in the base. Using the Briganti nomogram, his predicted risk of nodal involvement was 31%. He then underwent conventional imaging with CT chest, abdomen and pelvis as well as bone scan which demonstrated no evidence of nodal, visceral, or bony metastatic disease. He then underwent a Ga68-PSMA PET-CT which demonstrated one PSMA-positive lymph node along the left common iliac chain (consistent with miT2cN1M0 disease).
Dr. Ceci then discussed the role of PSMA PET-CT in this setting, for primary staging. He began highlighting that the 2020 updates of the EAU guidelines for staging of prostate cancer recommend the use of MRI for local staging in all patients with no further staging in low risk patients and cross-sectional imaging and bone scan in unfavourable intermediate and high-risk disease. Dr. Ceci then highlighted data from ProPSMA which demonstrated the superiority of PSMA PET-CT, as compared to CT and bone scan.
Further, this study demonstrated that PSMA PET-CT was much more likely to change clinical management, much less likely to provide equivocal findings, and, further, had lower overall radiation exposure.
Dr. Ceci presented further Phase III clinical data led by Dr. Thomas Hope and presented at the 2020 American Society of Clinical Oncology (ASCO 2020) Annual Meeting assessing PSMA PET-CT to stage lymph node metastases. This study had excellent inter-reader correlation. This study, similar to ProPSMA, demonstrated positive influences for treatment decisions. Additionally, the OSPREY trial presented by Dr. Preston Sprenkle at the 2020 American Urologic Association (AUA 2020) Annual Meeting demonstrated that positive predictive value (~85%) and negative predictive value (~80%) were quite high. Further, when micro-metastatic disease was excluded, the negative predictive value increased further.
A recent publication in European Urology examined the cost-effectiveness of the use of PSMA PET-CT demonstrating the dominance of PSMA PET-CT, based on cost savings and increased clinical detection of disease.
Dr. Ceci concluded that PSMA PET-CT increases lesion identification (with high specificity and positive predictive value) at lower cost and less radiation exposure. However, there are no data regarding survival benefits.
Dr. van der Poel then presented the opposing perspective. He began by highlighting that, based on systematic reviews, conventional imaging misses the majority of metastases. ProstaScint® was among the first approaches to “advanced” imaging in this disease space and had a marginal positive predictive value of 62% for nodal involvement. However, over time, image quality has improved and, as a result, so have results.
On the basis of data from a variety of sites and countries, Dr. van der Poel highlighted that the majority of small nodal metastases are missed by PSMA PET-CT: no nodes less than 2mm and only 27% of nodes 2-4mm were detectable on PSMA PET-CT. Further, patient and nodal level sensitivity differs substantially. As a result, a systematic review concluded that the sensitivity for small volume disease is too low to reasonably omit lymphadenectomy, particularly among larger studies.
Further, these patients with small volume metastatic disease are the ones who are mostly likely to derive a good outcome following treatment. Dr. van der Poel thus postulated that while PSMA PET-CT decreases the threshold at which metastases can be detected, the level still exceeds that of clinical relevance for curative intervention. Thus, given proven benefits of local therapy and nodal treatment in patients with cN1 disease in the pre-PSMA era, it is unlikely that the use of PSMA PET-CT, in his opinion, would change treatment approaches.
Dr. van der Poel further highlighted that, while the sensitivity of PSMA PET-CT was substantially higher than conventional imaging in ProPSMA, differences in specificity were quite small. Thus, while ProPSMA demonstrated a significant change in treatment, this may be a transition to undertreatment given changes from curative intent to palliative treatments. Further, he highlighted many benign and malignant non-prostate cancer disease that may lead to false positives on PSMA PET-CT.
Presented by: Sandro Gaspar, MD, MBA, Attending Urologist, Centro Hospitalar Lisboa Norte, TAP Air Portugal, Lisbon, Portugal; Francesco Ceci, MD, PhD, Assistant Professor, University of Turin, Turin, Italy; Henk van der Poel, MD, PhD, Antoni van Leeuwenhoek Hospital, Netherlands Cancer Institute, Amsterdam, The Netherlands
Written by: Christopher J.D. Wallis, MD, PhD, FRCSC, Instructor in Urology, Vanderbilt University Medical Center, Nashville, Tennessee, Twitter: @WallisCJD during the 18th Meeting of the EAU Section of Oncological Urology (ESOU21), January 29-31, 2021