San Francisco, California (UroToday.com) Over the last several years, PSMA PET has emerged as a useful advanced imaging modality across several disease spectrums of prostate cancer. At the localized prostate cancer session at ASCO GU 2020, Jeremie Calais, MD, from the University of California, Los Angeles discussed who should receive PSMA PET imaging in the current era of prostate cancer management. There are several tracers currently being utilized for PSMA PET imaging, including 68Ga-PSMA-I&T, 68Ga-PSMA-11, 18F-DCFPyL, 18F-rhPSMA, 18F-PSMA-1007, and 68-GA-PSMA-11 TLX591-CDX. But, as Dr. Calais points out, what is important is the biological target. As such, PSMA PET has been favored over choline PET and fluciclovine PET since PSMA overexpression is much greater than upregulated metabolism.
In terms of diagnostic performance of primary staging, PSMA PET is much more sensitive than bone scan for ruling out M1b disease. 
Marrow or lytic skeletal metastases are often missed by bone scan (no osteoblastic hyperactivity yet), whereas PSMA PET performs better in primary staging and BCR states, but not mCRPC as of yet. In a recently published meta-analysis of studies assessing PSMA PET’s ability to rule out pelvic N1 disease, sensitivity ranged from 23 to 100%, specificity 67-100%, positive predictive value 20-100%, and negative predictive value 41-100%.1 Weighted sensitivity was 59% and weighted specificity was 93%. Four studies compared PSMA PET with anatomical imaging (CT or MRI) and in all cases sensitivity and specificity were superior with PSMA PET. In data from UCLA, 277 men with intermediate and high-risk disease underwent 68GA-PSMA-11 finding a sensitivity of 38%, specificity of 94%, PPV of 70%, and NPV of 81% for detecting N1 disease.
PSMA PET may also have an impact on radiotherapy planning in that PSMA PET can show disease outside of the standard radiotherapy field in >16% of patients with intermediate and high-risk disease.2 With regards to T staging, there is only 40-50% of overlap/concordance between MRI and PSMA PET, as a significant proportion of cancers are potentially missed and underestimated by both MRI and PSMA PET. Recent interest has also been shown for PSMA PET guiding prostate biopsy targeting. PSMA PET signal intensity (SUVmax) correlates significantly with the Gleason grade, and SUVmax > 5 may predict clinically significant prostate cancer.
Dr. Calais notes that there are several points to consider for integrating PSMA PET into practice:
- There is likely to be a new definition of disease stage – for example conventional M0 disease may be PSMA M1; conventional N0 disease may be PSMA N1
- As of yet, we do not know the significance this advanced imaging has on management/outcomes: (i) If PSMA is negative, should the patient undergo surveillance? (ii) If PSMA shows T3 disease, should the patient have a non-nerve sparing prostatectomy? (iii) If the patient has PSMA positive ECE, should the patient not undergo a prostatectomy? (iv) If the patient has PSMA positive disease, should the patient have a radiotherapy boost and/or extended radiotherapy field coverage? (v) If the patient has PSMA positive disease, should the patient have systemic therapy?
- Cost-benefit assessments are needed
In Dr. Calais’ opinion, there are two groups of patients that should undergo advanced imaging in the current era:
- High-risk prostate cancer patients
- Patients with high suspicion of prostate cancer but negative biopsies/equivocal MRI
Presented by: Jeremie Calais, MD, University of California, Los Angeles, Los Angeles, CA.
Written By: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md, at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California.
References:
- Petersen LJ, Zacho HD. PSMA PET for primary lymph node staging of intermediate and high-risk prostate cancer: An expedited systematic review. Cancer Imaging 2020 Jan 23;20(1):10.
- Calais J, Kishan AU, Cao M, et al. Potential Impact of 68Ga-PSMA-11 PET/CT on the Planning of Definitive Radiation Therapy for Prostate Cancer. J Nucl Med 2018 Nov;59(11):1714-1721.