ASCO GU 2021: Welcome to the Wild West: The Impact of the FDA Approval of PSMA PET/CT on Prostate Cancer Management

( The practical applications of novel imaging and genomic approaches in the management of clinically localized prostate cancer session at the 2021 ASCO Genitourinary Cancers Symposium (ASCO GU), included a presentation by Dr. Declan Murphy who discussed the Impact of the Federal Drug Administration (FDA) approval of PSMA PET/CT in prostate cancer management. The FDA approval was recently granted in the United States (US) for use of PSMA PET/CT, but only at two centers: UCLA and UCSF. Since PSMA PET/CT has been used for many years in Australia, Dr. Murphy is able to provide insights into how utilization of this novel imaging technology may look in the US over the coming months/years (the good, the bad and the ugly!).

Dr. Murphy notes that PSMA PET/CT is excellent for the staging of high-risk prostate cancer. Last year, he and his colleagues published the proPSMA study in The Lancet.1 To be eligible for inclusion in this trial, men must have had at least one high-risk factor including PSA >= 20 ng/mL, ISUP grade group 3-5, or clinical stage T3 or greater. Patients who had undergoing staging investigations (apart from prostate MRI) within eight weeks prior to randomization were excluded. Following enrollment, patients were randomly assigned in a 1:1 ratio to either conventional imaging performed using bone scan and CT or PSMA PET/CT. Patients who were randomized to conventional imaging underwent an abdominopelvic CT scan with contrast as well as a technetium-99m bone scan with SPECT CT of chest, abdomen, and pelvic in keeping with the standard of care. For patients randomized to PET/CT, gallium-68 PSMA-11 PET/CT was performed. In patients who had fewer than three unequivocal sites of metastasis, cross-over imaging for confirmation was performed within 14 days. Confirmatory testing following imaging was performed at the discretion of the treating physician and included biopsy confirmation.

Between 2017 and 2018, the authors randomly assigned 302 patients of whom 300 received assigned first-line imaging. In the primary outcome assessment, PSMA PET-CT had a 27% absolute greater AUC for accuracy compared to conventional imaging (95% CI 23-31): 92% (95% CI 88-95%) vs. 65% (60-69%). Conventional imaging had both a lower sensitivity (38% vs. 85%) and also a lower specificity (91% vs. 98%). Prior to treatment, the results of conventional imaging studies resulted in treatment change for 23 men (15%, 95% CI 10-22) while the results of PSMA PET-CT resulted in treatment change for 41 (28%, 95% confidence interval 21-36). These changes included both a transition from curative intent to palliative intent treatment in 20 patients (14%) and also a change in treatment approach in 22 (14%). Additionally, conventional imaging was associated with a higher radiation dose (19.2 mSv compared to 8.4 mSv; absolute difference 10.9 mSv, 95% CI 9.8-12.0 mSv0. PSMA PET-CT was not associated with any adverse events and reporter agreement was high for both nodal (kappa 0.87, 95% CI 0.81-0.94) and distant metastatic disease (kappa 0.88, 95% CI 0.94-0.92).

Part of the trial design was a built-in health economics perspective, and Dr. Murphy and colleagues recently published this analysis in European Urology.2 They found that the estimated cost per scan for PSMA PET/CT was AUD$1203, which was less than the conventional imaging cost at AUD$1412. 


PSMA PET/CT was thus dominant, having both better accuracy and a lower cost, resulting in a cost of AUD$959 saved per additional accurate detection of nodal disease, and AUD$1412 saved for additional accurate detection of distant metastases. Additionally, these results were most sensitive to variations in the number of men scanned for each 68Ga-PSMA-11 production run. As such, Dr. Murphy’s group suggests that PSMA PET/CT should replace conventional staging for me with newly diagnosed high-risk prostate cancer as outlined in the following figure:


However, Dr. Murphy notes that there are some uncertainties with regards to PSMA PET/CT. For instance, does the utilization of this novel imaging improve outcomes in our high-risk prostate cancer patients? Dr. Murphy provided two scenarios for discussion:

  • Does the lymph node status help for surgical or radiation planning for these patients and does this improve outcomes? PSMA PET/CT has high specificity for pelvic lymph node detection, and thus positive lymph nodes would guide one to do a thorough lymph node dissection that should correlate with histopathology, or plan appropriate primary nodal radiation. However, no imaging modality to date is able to visualize lymph node tumor involvement <3 mm. 
  • Does the presence of distant disease save patients from futile local therapies? A patient with negative conventional imaging but positive PSMA PET/CT retroperitoneal nodal disease would avoid local therapy and would be more appropriately treated with maximal systemic therapy plus radiotherapy for his M1a disease.

Ultimately, at this point in time, we do not know if the improved accuracy of staging with PSMA PET/CT is improving the survival of our patients. Dr. Murphy notes that we need to build novel imaging into the design of future clinical trials, as his group is doing with the UpFrontPSMA trial (TPS180 at GU ASCO 2021):


Dr. Murphy notes that perhaps the “ugly” part of PSMA PET/CT imaging is in the biochemical recurrence after radical prostatectomy disease state. He has seen patients receive a PSMA PET/CT scan when their PSA reaches 0.02 ng/mL and if negative are being followed with serial PSMA PET/CT scans until the scans is positive, as the PSA continues to rise. He notes that there is ample evidence suggesting that early salvage RT is standard of care, and we must not wait until the PSMA PET/CT scan is positive in these patients for the risk of losing the window for early salvage radiotherapy.

Looking back on his use of PSMA PET/CT over the last 6 six years, Dr. Murphy notes that he cannot imagine advanced prostate cancer without this novel imaging and believes that as we get used to utilizing this new technology we will improve outcomes for our patients. Additionally, we must not be afraid of the disruption of conventional wisdom that utilization of PSMA PET/CT will bring and that we must learn from each other’s prior experiences.


Presented by: Declan G. Murphy, MB, BCH, BaO, FRACS, FRCS, Professor, Urologist & Director of GU Oncology, Peter MacCallum Cancer Centre, Associate Editor, BJUI, Honorary Clinical Professor, The University of Melbourne

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md during the 2021 ASCO Genitourinary Cancers Symposium (ASCO GU), February 11th to 13th, 2021

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 Apr 11;395(10231):1208-1216.
2. De Feria Cardet RE, Hofman MS, Segard T, et al. Is Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Imaging Cost-effective in Prostate Cancer: An Analysis Informed by the proPSMA Trial. Eur Urol. 2020 Dec 16;S0302-2838(20)30946-5.

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