The Role of PSMA PET/CT Imaging in Diagnosing and Staging Prostate Cancer in Practice

Prostate cancer is one of the most common cancers in men in the United States with increasing incidence rates noted over the last 9 years.¹ The introduction of prostate-specific membrane antigen (PSMA)-directed positron emission tomography/computed tomography (PET/CT) is leading to improved diagnosis and staging of prostate cancer and many clinicians are choosing it over conventional imaging options.^2-4 PSMA PET/CT imaging is recommended for patients with metastatic disease or who are likely to have metastatic disease where it has been shown to have benefit over conventional imaging.^2,3,5

In the United Sates, the first PSMA-targeted PET imaging drug for men with prostate cancer was approved in December 2020.⁶ Currently, FDA-approved PSMA tracers include gallium 68 (⁶⁸Ga) PSMA-11 (also known as Ga 68 gozetotide), fluorine 18 (¹⁸F)- DCFPyL (also known as piflufolastat F-18), and ¹⁸F-rhPSMA-7.3 (also known as flotufolastat F-18).^7-10

The FDA-approved ⁶⁸Ga-labeled PSMA-11 is currently indicated for PET of PSMA-positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy, with suspected recurrence based on elevated serum PSA level, and for selection of patients with metastatic prostate cancer for whom lutetium ¹⁷⁷Lu vipivotide tetraxetan PSMA-directed therapy is indicated.¹¹ A kit for the preparation of ⁶⁸Ga gozetotide injectionit is approved for the same indications.¹² F-18–labeled piflufolastat F-18 is FDA approved for PET of PSMA-positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or who have a suspected recurrence based on their elevated serum PSA levels.¹³ And The flotufolastat F-18 injection, formerly ¹⁸F-rhPSMA-7.3, was approved in May 2023 for PET of PSMA-positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or who have suspected recurrence based on elevated serum PSA level.¹⁴

The main difference between these compounds is their production and use based on institutional resources and supplier availability. ⁶⁸Ga has a 68-minute half-life, affecting delivery and compounding timing. Production requires a generator or commercially available cold kits. 18F compounds are made by a cyclotron, either in-house or by an external supplier. ¹⁸F has a half-life of 110 minutes, which influences the ordering and scanning schedule.¹⁵ These FDA-approved agents are similar in use and detection efficacy for primary and metastatic disease and use of PSMA PET/CT in certain settings is recommended instead of the use of conventional imaging by several clinical guidelines for the management of prostate cancer.

Guideline recommendations for PSMA PET CT in prostate cancer

Clinical guidelines from the National Comprehensive Cancer Network (NCCN), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Nuclear Medicine (EANM), the American Urological Association (AUA), and the Society of Urologic Oncology (SUO) are generally in agreement for the recommended clinical use and application of PSMA PET/CT in prostate cancer. There is a consensus among various panels for its use in initial staging for suspected metastases, biochemical recurrence based on elevated PSA, nonmetastatic castration-resistant prostate cancer with elevated PSA, monitoring for progression in advanced prostate cancer, and eligibility for PSMA-directed radioligand therapy.^3,5,16 The NCCN recommends it as the preferred alternative to conventional imaging when metastasis or increase of PSA after definitive therapy is a concern. As the NCCN guidelines advocate its use as a primary therapy in patients for whom it is suitable, the adoption of PSMA PET/CT is likely to increase.

The clinical use of PSMA PET/CT—either in combination with conventional imaging or by itself to replace conventional means—can vary. In patients with PSA recurrence after local therapy has failed, clinicians utilize PSMA PET/CT imaging preferentially, when available, as an alternative to conventional imaging due to its greater sensitivity. They also may use it if conventional imaging is negative.^5,16

Additionally, the recent joint guideline by the SNMMI and the EANM provides valuable insights into potential pitfalls of approved compounds. It emphasizes the need for radiologists and nuclear medicine physicians to be well-informed and discerning, especially with benign lesions; PSMA may be detected in non-prostate or benign tumors.

Results from a retrospective study of ⁶⁸Ga-PSMA-11 vs F-labeled compounds suggest that F-18 compounds might have higher clinically insignificant bone uptake due to the nature of F-18, possibly leading to more benign or indeterminate readings.¹⁷ However, the data in this area is sparse.

Looking ahead

Based on available data, PSMA PET/CT scans have started to change patient management, and time will reveal the long-term benefits of these changes.^18-21 Studies have demonstrated that PSMA PET/CT results may provide useful information that could result in changes to treatment recommendations. A study by Sonni et al. found that ⁶⁸Ga-PSMA-11 PET/CT results changed the up- or downstaging of disease in 69% of patients and led to a change in disease management in more than half of patients.¹⁹ Another study by Müller et al. showed similar findings.²⁰ PSMA PET/CT identified recurrence in 74% of patients with a detection rate of 50% at PSA values of less than 0.5 ng/ml. And ⁶⁸Ga-PSMA-11 PET results changed the management of the disease in 60% of patients. Additionally, a secondary analysis of the phase 3 CONDOR study (NCT03739684), which evaluated ¹⁸F-DCFPyL PET/CT in men with biochemical recurrent prostate cancer, found that 39% of men with PSA levels of 0.5 ng/mL or less had a change in intended management of their disease.²¹

The future of emerging and investigative PSMA PET/CT imagine is promising and could continue to reshape patient care and treatment paradigms in the coming decade. As with any medical advancement, collaboration between urologists and radiologists is crucial. Their combined expertise ensures accurate interpretation of scans, which will lead to better patient outcomes.

References

1. American Cancer Society. Key Statistics for Prostate Cancer. Revised October 8, 2021. Accessed September 26, 2023. https://www.cancer.org/content/dam/CRC/PDF/Public/8793.00.pdf

2. 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. Doi:10.1016/S0140-6736(20)30314-7

3. Fendler WP, Eiber M, Beheshti M, et al. PSMA PET/CT: joint EANM procedure guideline/SNMMI procedure standard for prostate cancer imaging 2.0. Eur J Nucl Med Mol Imaging. 2023;50(5):1466-1486. Doi:10.1007/s00259-022-06089-w

4 Briganti A, Abdollah F, Nini A, et al. Performance characteristics of computed tomography in detecting lymph node metastases in contemporary patients with prostate cancer treated with extended pelvic lymph node dissection. Eur Urol. 2012;61(6):1132-1138. Doi:10.1016/j.eururo.2011.11.008

5. NCCN. Clinical Practice Guidelines in Oncology. Prostate cancer, version 4.2023. Accessed October 3, 2023. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf

6. FDA approves first PSMA-targeted PET imaging drug for men with prostate cancer. News release. FDA. December 1, 2020. Accessed October 5, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-psma-targeted-pet-imaging-drug-men-prostate-cancer

7. FDA approves Telix’s prostate cancer imaging product, Illuccix. Published online December 20, 2021. Accessed October 5, 2023. https://telixpharma.com/news-views/fda-approves-telixs-prostate-cancer-imaging-product-illuccix/

8. Lantheus receives U.S. FDA approval of PYLARIFY® (piflufolastat F 18) injection, the first and only commercially available PSMA PET imaging agent for prostate cancer. Published online May 27, 2021. Accessed October 5, 2023. https://investor.lantheus.com/news-releases/news-release-details/lantheus-receives-us-fda-approval-pylarifyr-piflufolastat-f-18

9. US FDA approves Blue Earth Diagnostics’ Posluma (flotufolastat F-18 injection, first radiohybrid PSMA-targeted PET imaging agent for prostate cancer. News release. Blue Earth Diagnostics. May 30, 2023. Accessed October 5, 2023. https://www.businesswire.com/news/home/20230530005180/en/U.S.-FDA-Approves-Blue-Earth-Diagnostics%E2%80%99-POSLUMA%C2%AE-Flotufolastat-F-18-Injection-First-Radiohybrid-PSMA-targeted-PET-Imaging-Agent-for-Prostate-Cancer

10. Novartis Pluvicto™ approved by FDA as first targeted radioligand therapy for treatment of progressive, PSMA positive metastatic castration-resistant prostate cancer. Press release. Novartis. March 23, 2022. Accessed October 5, 2023. https://www.novartis.com/news/media-releases/novartis-pluvictotm-approved-fda-first-targeted-radioligand-therapy-treatment-progressive-psma-positive-metastatic-castration-resistant-prostate-cancer

11. Illuccix. Prescribing Information. Telix Pharmaceuticals; 2023. Accessed October 12, 2023. https://illuccixhcp.com/wp-content/uploads/illuccix-prescribing-information.pdf

12. Locametz. Prescribing Information. Novartis; 2023. Accessed October 12, 2023. https://www.novartis.com/us-en/sites/novartis_us/files/locametz.pdf

13. Pylarify. Prescribing Information. Progenics Pharmaceuticals; 2023. Accessed October 12, 2023. https://www.pylarify.com/sites/default/files/resources/prescribing-information.pdf

14. Posluma. Prescribing Information. Blue Earth Diagnostics; 2023. Accessed October 12, 2023. https://www.posluma.com/prescribing-information.pdf

15. Werner RA, Derlin T, Lapa C, et al. 18F-labeled, PSMA-targeted radiotracers: leveraging the advantages of radiofluorination for prostate cancer molecular imaging. Theranostics. 2020;10(1):1-16. doi:10.7150/thno.37894

16. Lowrance W, Dreicer R, Jarrard DF, et al. Updates to advanced prostate cancer: AUA/SUO guideline (2023). J Urol. 2023;209(6):1082-1090. Doi:10.1097/JU.0000000000003452

17. Rauscher I, Krönke M, König M, et al. Matched-pair comparison of 68Ga-PSMA-11 PET/CT and 18F-PSMA-1007 PET/CT: frequency of pitfalls and detection efficacy in biochemical recurrence after radical prostatectomy. J Nucl Med. 2020;61(1):51-57. doi:10.2967/jnumed.119.229187

18. Hofman MS. ProPSMA: A callout to the nuclear medicine community to change practices with prospective, high-quality data. J Nucl Med. 2020;61(5):676-677. Doi:10.2967/jnumed.120.245647

19. Sonni I, Eiber M, Fendler WP, et al. Impact of 68Ga-PSMA-11 PET/CT on staging and management of prostate cancer patients in various clinical settings: a prospective single-center study. J Nucl Med. 2020;61(8):1153-1160. doi:10.2967/jnumed.119.237602

20. Müller J, Ferraro DA, Muehlematter UJ, et al. Clinical impact of 68Ga-PSMA-11 PET on patient management and outcome, including all patients referred for an increase in PSA level during the first year after its clinical introduction. Eur J Nucl Med Mol Imaging. 2019;46(4):889-900. doi:10.1007/s00259-018-4203-0

21. Pouliot F, Gorin MA, Rowe SP, et al. Changes in planned disease management after piflufolastat F18 PET/CT in men with biochemically recurrent prostate cancer and low PSA levels: a secondary analysis of results from the CONDOR study. J Clin Oncol. 2023;41(suppl 6; Abstract 61). doi:10.1200/JCO.2023.41.6_suppl.61