Society of Urologic Oncology (SUO) 21st Annual Meeting

SUO 2020: Impact of PSMA Scans on Clinical Management - PSMA PET-CT is Not Ready for Prime-Time Use

(UroToday.com) In a point and counterpoint format at the 2020 Society of Urologic Oncology (SUO) Annual Virtual Meeting discussing whether prostate-specific membrane antigen (PSMA) PET-CT is ready for prime-time use, Dr. Matthew Cooperberg took the counterpoint approach that PSMA PET-CT is not yet ready for prime-time use.

Dr. Cooperberg notes that in 2020, the standard of care for staging remains bone scan and CT or MRI. Among the PET/CT tracers, only 11C-choline and 18F-fluciclovine are FDA approved for the workup of recurrent prostate cancer. The staging for distant disease is definitely better with PSMA (better than fluciclovine), which in turn is better than choline PET/CT. According to a 2019 systematic review and meta-analysis assessing 21 studies with 3,202 participants,1 the sensitivity for each trace was 11C-choline 80.9% (95% confidence interval [CI] 70.4-88.3%), 18F-FACBC 79.7% (95% CI 51.9-93.4%), and 68Ga-PSMA 76.4% (95% CI 68.3-82.9%). The corresponding summary specificity was 11C-choline 84.1% (95% CI 70.2-92.2%), 18F-FACBC 61.9% (95% CI 41.1-79.0%), and 68Ga-PSMA 99.8% (95% CI 97.5-100%).

So, Dr. Cooperberg asks, PSMA is the best, but how good is it? A systematic review and meta-analysis published by Perera et al. in 2020 assessed 37 articles including 4,790 patients.2 For patients with biochemical recurrence, the percentage of positive scans were 33% for prostate-specific antigen (PSA) 0-0.19 ng/mL, 45% for PSA 0.2-0.49, 59% for PSA 0.50-0.99, 75% for PSA 1-1.99, and 95% for PSA ≥ 2 ng/mL. Additionally, there were significant differences in positivity after biochemical recurrence in the prostate bed that were noted between radical prostatectomy (22%) and radiotherapy (52%) patients.

Even though PSMA is good, how good is rather unclear because most studies do not determine the false-positive nor the false-negative rate. As such, this has led to a Will Rogers phenomenon for stage migration in prostate cancer. For example, on bone scan, if there are 10 “M1” patients with high burden disease, they fail treatment quickly; if there are 90 “M0” patients, some will be false-negative and have intermediate outcomes. If these same patients were given a PSMA PET-CT, there may be 33 “M1” patients with lower disease burden, that will fail treatment later; if there are 67 “M0” patients, there will be fewer false negatives, and they will have better outcomes overall.

Every trial of “M0” or “M1” prostate cancer over the last 20 years, whether in localized disease or castration-resistant prostate cancer (CRPC), has defined both eligibility and outcomes based on a 99Tc bone scan. How should PET/CT guide primary treatment? Utilization of lymph node dissection? Salvage lymph node dissection? SABR? Systemic treatment response? There is some data to guide us as to whether we should go after PET-positive lesions. A systematic review and meta-analysis among patients that underwent PSMA PET-CT imaging followed by salvage lymph node dissection among 14 studies and 462 patients found that the positive predictive value of PSMA-PET before salvage lymph node dissection on a patient-based analysis ranged between 0.70 and 0.93. The field-based sensitivity was 0.82 (95% CI 0.72-0.89) and specificity was 0.95 (95% CI 0.70-0.99).

The SABR-COMET trial randomized 99 patients with solid organ malignancies and oligometastatic disease to either the SABR group (67%) or the control group (33%).4 The median overall survival was 28 months (95% CI 19–33) in the control group versus 41 months (26–not reached) in the SABR group (HR 0.57, 95% CI 0.30–1.10; p=0.090):

SABR COMET trial overall survival

Dr. Cooperberg cautions that in this trial, there were very few prostate cancer patients (21% SABR group, 6% control group), so outcomes may not be completely generalizable to all prostate cancer patients. He finished his presentation with several concluding thoughts:

  • Imaging tests are biomarkers and must be evaluated in light of all the available clinical information
  • PSMA PET/CT, in particular, is changing what we understand about prostate cancer biology, and is effective as a massive stage migration from “M1” to “M0”: in 2020 we have no idea (yet) what to do with these results
  • Theranostics are promising and intraoperative imaging could be very cool
  • The future is extremely exciting, and we need to be planning the trials to figure out how to use the tools we have now and will have very soon

Presented by: Matthew Cooperberg, MD, MPH, FACS, Professor of Urology, Epidemiology & Biostatistics, Helen Diller Family Chair in Urology, The University of California San Francisco, San Francisco, California

Written by: Zachary Klaassen, MD, MSc, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Augusta, Georgia, Twitter: @zklaassen_md at the 2020 Society of Urologic Oncology Annual Meeting – December 2-5, 2020 – Washington, DC

References:

1. Sathianathen, Niranjan J., Mohit Butaney, and Badrinath R. Konety. "The utility of PET-based imaging for prostate cancer biochemical recurrence: a systematic review and meta-analysis." World journal of urology 37, no. 7 (2019): 1239-1249.

2. Perera, Marlon, Nathan Papa, Matthew Roberts, Michael Williams, Cristian Udovicich, Ian Vela, Daniel Christidis et al. "Gallium-68 prostate-specific membrane antigen positron emission tomography in advanced prostate cancer—updated diagnostic utility, sensitivity, specificity, and distribution of prostate-specific membrane antigen-avid lesions: a systematic review and meta-analysis." European urology 77, no. 4 (2020): 403-417.

3. Kimura, Shoji, Mohammad Abufaraj, Florian Janisch, Takehiro Iwata, Mehdi Kardoust Parizi, Beat Foerster, Nicola Fossati et al. "Performance of [68 Ga] Ga-PSMA 11 PET for detecting prostate cancer in the lymph nodes before salvage lymph node dissection: a systematic review and meta-analysis." Prostate cancer and prostatic diseases 23, no. 1 (2020): 1-10.

4. Palma, David A., Robert Olson, Stephen Harrow, Stewart Gaede, Alexander V. Louie, Cornelis Haasbeek, Liam Mulroy et al. "Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial." The Lancet 393, no. 10185 (2019): 2051-2058.

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