Rapid Guideline Update on Radiotracers for Determining Radioligand Treatment Eligibility in Metastatic Castration-Resistant Prostate Cancer

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ASCO has released a guideline rapid recommendation update addressing radiotracers used for prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) diagnostic imaging for selecting patients with metastatic castration-resistant prostate cancer (mCRPC) to receive lutetium-177–labeled PSMA-617 (LuPSMA) radioligand therapy.1 The new recommendation, which updates the initial 2014 guideline and subsequent 2022 update, recommends three radiotracers, including the newly approved flotufolastat F-18, to determine eligibility in mCRPC.2,3

New Approval Ushers Rapid Recommendation Update

The 2014 ASCO guideline on systemic therapy in men with mCRPC was updated in 2022 to include recommended guidance on the use of LuPSMA, which delivers targeted beta-particle radiation to PSMA-expressing cancer cells.2,3

According to Rohan Garje, MD, of Miami Cancer Institute, and Guideline Co-Chair, gallium Ga-68–PSMA-11 (Ga-68–PSMA-11) was initially recommended to be used as a radiotracer for patient selection at the time of U.S. Food and Drug Administration (FDA) approval of LuPSMA, as this was the only diagnostic agent used for patient selection in the phase III VISION trial.4,5

Rohan Garje, MD

Rohan Garje, MD

In late May 2023, the FDA approved the use of flotufolastat F-18 in mCRPC based on the results of the phase III LIGHTHOUSE and SPOTLIGHT trials.6-8 These trials showed that flotufolastat F-18 injection was able to detect distant metastatic lesions and demonstrated a clinically meaningful correct detection rate in prostate cancer.

Dr. Garje explained that there are now three PSMA PET radiopharmaceutical imaging agents approved by the FDA for patients with localized PSMA-positive disease at initial staging and at the time of biochemical recurrence: Ga-68–PSMA-11, piflufolastat F-18, and flotufolastat F-18.

The new guideline recommendation update reflects the newest approval of flotufolastat F-18, according to the guideline Expert Panel. “Given the availability of these additional imaging agents, an update to our current guideline recommendations [was] done to add flotufolastat F-18 to previously recommended Ga-68–PSMA-11 and piflufolastat F-18 as an additional imaging agent for patient selection,” Dr. Garje said.

New Guideline Recommendation

The new recommendation was formed according to a targeted electronic literature search. Although the literature search was used to identify additional radiotracers, beyond flotufolastat F-18 alone, for the mCRPC population, the Expert Panel noted that none were found.

For the new recommendation, the guideline Expert Panel currently recommends the use of either Ga-68–PSMA-11, piflufolastat F-18, or flotufolastat F-18 as radiotracers to determine treatment eligibility. The guideline Expert Panel noted its support for checking blood cell counts and renal and hepatic function before each treatment cycle. Additionally, the panel stated it supports multidisciplinary collaboration for the use of LuPSMA, if possible.

The updated recommendation featured low evidence quality and a weak strength of recommendation and was based on an Expert Panel consensus rather than clinical trial evidence. “Although there are no specific clinical trials to support our recommendation,” Dr. Garje said, “the addition of other imaging agents is primarily to expand access to LuPSMA therapy by not restricting patient selection based on Ga-68–PSMA-11 alone.”

Concluding Thoughts

The Expert Panel concluded that further and complete updates to the ASCO mCRPC guidelines are currently underway.

Dr. Garje noted there is ongoing research to better identify methods for patient selection for these radiopharmaceutical agents to identify the ones who benefit the most. The ongoing guideline update will also address the utility of PARP inhibitor–based combination therapies and biomarker testing and will provide guidance on sequencing of therapies for patients with mCRPC.

In addition, Dr. Garje said therapy with -LuPSMA is now moving to earlier lines of treatment prior to chemotherapy in castration-sensitive -(PSMAddition trial; identifier NCT04720157) and castration-resistant -(PSMAfore trial; NCT04689828) settings. “These studies, if positive, will help move this promising therapy to earlier lines,” he said. 


1. Garje R, Rumble RB, Parikh RA: Systemic therapy update on 177lutetium-PSMA-617 for metastatic castration-resistant prostate cancer: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. November 6, 2023 (early release online).

2. Basch E, Loblaw DA, Oliver TK, et al: Systemic therapy in men with metastatic castration-resistant prostate cancer: American Society of Clinical Oncology and Cancer Care Ontario clinical practice guideline. J Clin Oncol 32:3436-3448, 2014.

3. Garje R, Rumble RB, Parikh RA: Systemic therapy update on 177lutetium-PSMA-617 for metastatic castration-resistant prostate cancer: ASCO rapid recommendation. J Clin Oncol 40:3664-3666, 2022.

4. Sartor O, de Bono J, Chi KN, et al; VISION Investigators: Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med 385:1091-1103, 2021.

5. U.S. Food and Drug Administration: FDA D.I.S.C.O. Burst Edition: FDA approval of Pluvicto (lutetium Lu 177 vipivotide tetraxetan) for the treatment of adult patients with prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. Updated April 22, 2022. Available at Accessed January 4, 2024.

6. Heo YA: Flotufolastat F 18: Diagnostic first approval. Mol Diagn Ther 27:631-636, 2023.

7. Jani AB, Ravizzini GC, Gartrell BA, et al; SPOTLIGHT Study Group: Diagnostic performance and safety of 18F-rhPSMA-7.3 positron emission tomography in men with suspected prostate cancer recurrence: Results from a phase 3, prospective, multicenter study (SPOTLIGHT). J Urol 210:299-311, 2023.

8. Surasi DS, Eiber M, Maurer T, et al; LIGHTHOUSE Study Group. Diagnostic performance and safety of positron emission tomography with 18F-rhPSMA-7.3 in patients with newly diagnosed unfavourable intermediate- to very-high-risk prostate cancer: Results from a phase 3, Pprospective, multicentre study (LIGHTHOUSE). Eur Urol 84:361-370, 2023.

Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, November 8, 2023. All rights reserved.