The most recent American Society of Clinical Oncology (ASCO) guidelines for the management of metastatic castration-resistant prostate cancer (mCRPC) was published in 2014. The field is primed for an update to these guidelines as several clinical and investigational advances have emerged in the management of mCRPC since the 2014 recommendations were released. At the top of the list of advances is the radioligand therapy Lutetium-177-PSMA-617 (^₁₇₇Lu-PSMA-617) which delivers targeted beta-particle radiation to cancer cells that express the prostate-specific membrane antigen (PSMA).

Lu-PSMA-617 has been shown in a landmark clinical trial to improve radiographic progression-free survival and overall survival (OS) in patients with PSMA-positive mCRPC² and received approval from the US Food and Drug Administration (FDA) in March 2022.

In advance of the imminent comprehensive update to the ASCO guidelines for systemic therapy in mCRPC, the society has released a rapid recommendation supporting the use of ¹⁷⁷Lu-PSMA-617 in this patient population⁴. These rapid recommendations which will function as an update to the full 2014 guidelines were put together by a panel of experts convened by ASCO. Rohan Garje, MD, who recently became the Chief of Genitourinary Medical Oncology at Baptist Health Miami Cancer Institute was one of the co-chairs for the panel.

The panel met earlier this year to review the literature and create evidence-­based recommendations for ¹⁷⁷Lu-PSMA-617 utilization in prostate cancer. Following a thorough literature review, the panel identified ten critical studies that informed the creation of new guidelines, four of which were randomized trials and six of which were observational studies. All the randomized trials showed improvements in quality-of-life outcomes with ¹⁷⁷Lu-PSMA-617 and reports from the observational studies demonstrated decreased brief pain inventory severity and interference scores. The recommendations made by the panel include: 

Updated Recommendation 1.1

The panel recommends the use of ¹⁷⁷Lu-PSMA-617 IV once every 6 weeks for 4-6 cycles as a treatment option in patients with PSMA PET/CT-positive mCRPC who have progressed on one prior line of androgen receptor pathway inhibitor and at least one line of prior chemotherapy

Updated Recommendation 1.2.1

The panel recommends that patients should be selected with PSMA PET

Updated Recommendation 1.2.2

The panel recommends that either Ga-68 PSMA-11 or F-18 piflufolastat be used as radiotracers to determine eligibility

These guidelines aim to assist providers in clinical decision making as they manage patients with advanced forms of prostate cancer. The full publication in the Journal of Clinical Oncology (JCO) is available here.

References

1. 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

2. Sartor 0, de Bono J, Chi KN, et al: Lutetiurn-177-PSMA-617 for metastatic castration­resistant prostate cancer. N Engl J Med 385:1091-1103, 2021

3. Medicine S of N. FDA Approves Pluvicto/Locarnetz for Metastatic Castration-Resistant Prostate Cancer. Journal of Nuclear Medicine. 2022;63(5):13N-13N.
https://jnrn.snrnjournals.org/content/63/5/13N.2/tab-article-info Web. Accessed 14 Oct 2022.

4. Systemic Therapy Update on 177Lutetium-PSMA-617 for Metastatic Castration­Resistant Prostate Cancer: ASCO Rapid Recommendation Rohan Garje, R. Bryan Rumble, and Rahul A. Parikh. Journal of Clinical Oncology 2022 40:31, 3664-3666