In the setting of previously treated metastatic castration-resistant prostate cancer (mCRPC), where treatment options may become limited, having options can be meaningful to patients and may provide opportunities to individualize treatment. For example, a patient with mCRPC who has progressed after docetaxel and androgen receptor–targeted therapy may be a candidate for cabazitaxel; however, if this individual must travel a good distance to receive treatments, he might prefer ¹⁷⁷Lu-PSMA-617 (also referred to as lutetium Lu 177 vipivotide tetraxetan) based on the lower treatment frequency of approximately once every 6 weeks for 4 to 6 cycles.

Personalized treatment also includes tailoring a specific therapy to a specific patient. In the case of PSMA-targeted radioligand therapy, researchers are just beginning to work on personalized therapy. At the 2023 SNMMI Annual Meeting, several studies reflected early efforts to refine patient selection and optimize therapeutic activity so that more patients can derive the maximal benefit.

A few presentations focused on the safety of PSMA-targeted radioligand therapy in patients who may be at greater risk for treatment-related toxicities. For instance, Abdelrazek et al examined the adverse events occurring during or shortly after treatment with ¹⁷⁷Lu-PSMA at the Mayo Clinic, identifying 185 eligible patients for analysis (poster P1018). Overall, they found that mild to moderate short-term side effects that are secondary to treatment with ¹⁷⁷Lu-PSMA can be mostly managed in an outpatient setting. They also found an association between higher Eastern Cooperative Oncology Group performance scores and increased post-treatment emergency department visits and hospital admissions.

Also at the SNMMI meeting, Langbein and colleagues considered the safety of ¹⁷⁷Lu-PSMA-I&T, another ¹⁷⁷Lu-PSMA–targeted radioligand therapy that is currently in phase 3 clinical trials, in the 80-and-over age group (poster P1229). They reported that ¹⁷⁷Lu-PSMA-I&T in elderly patients with mCRPC was safe and effective, findings that are comparable to previously published data of non–age-selected cohorts. For example, in a previous study of 100 patients by Heck et al, ¹⁷⁷Lu-PSMA-I&T showed good activity in more than one-third of patients with late-stage mCRPC at low toxicity.

Patients with mCRPC may vary in their access to PSMA positron emission tomography (PET) imaging based on where they receive care. Clinical trials such as VISION and TheraP both report the efficacy of ¹⁷⁷Lu-PSMA-617 therapy utilizing ⁶⁸Ga-PSMA-11 PET/computed tomography (CT) imaging for patient selection. ⁶⁸Ga-PSMA-11 received US Food and Drug Administration approval prior to ¹⁸F-DCFPyL PSMA PET/CT, but both are now available, so there is interest in whether ¹⁸F-DCFPyL can be used much like ⁶⁸Ga-PSMA-11 to select patients for ¹⁷⁷Lu-PSMA-617 treatment.

At the conference, researchers from the University of California, San Francisco pursued this question using available data from their institution (poster P1249). Kim et al identified 61 patients who received ¹⁷⁷Lu-PSMA-617 therapy, 35 of whom received ⁶⁸Ga-PSMA-11 and 26 of whom received ¹⁸F-DCFPyL. They found that the physiologic biodistributions for ⁶⁸Ga-PSMA-11 and ¹⁸F-DCFPyL were similar between groups; the best post–¹⁷⁷Lu-PSMA-617 therapy response was also similar between groups (ie, prostate-specific antigen–50 in 43% of patients imaged with ⁶⁸Ga-PSMA-11 and in 47% of those imaged with ¹⁸F-DCFPyL). The authors concluded that their findings suggest that individuals may be safely selected for ¹⁷⁷Lu-PSMA-617 treatment using either ¹⁸F-DCFPyL or ⁶⁸Ga-PSMA-11, but prospective comparison must be performed.

Ultimately, verifying PSMA positivity with a PSMA PET scan might just be the first step in personalized PSMA-targeted radioligand therapy. Researchers hope to further develop both predictive biomarkers and biomarkers for use in response assessment. For example, in poster P507, also presented at the SNMMI meeting, Emmett and colleagues explored the possibility of personalizing ¹⁷⁷Lu-PSMA dosing intervals using early response biomarkers, noting that such strategies might allow for the achievement of similar overall treatment responses to that of standard dosing schedules while allowing for therapy changes in nonresponders or even treatment holidays in excellent responders.

Researchers are also seeking to develop predictive markers other than the presence of the target in the tumors. An example of work in this area from the meeting is a single-center pilot experience by Kulkarni et al, who studied ATM mutations and a reduction in molecular tumor volume on single-photon emission CT/CT as potential predictors of a favorable response to treatment with ¹⁷⁷Lu-PSMA-617 (poster P1429). Researchers also noted that future clinical trials will examine the integration of different patient and disease features with individual post-therapeutic dosimetry for further treatment personalization.