Dose optimization of prostate-specific membrane antigen (PSMA)–targeted radioligand therapy (RLT) is an active area of research. In the future, personalized dosing might enhance the ability to effectively treat the tumor while reducing treatment-related side effects, thereby benefiting health-related QOL (HRQOL). 

Currently, there is a need to better understand absorbed dose–effect relationships that might aid in patient-specific personalization. At the 2023 SNMMI Annual Meeting, researchers approached personalized PSMA-targeted RLT dosimetry from different angles. Chen et al were interested in the application of deep learning to help streamline patient-specific dosimetry (poster P690). Organ segmentation in imaging enables quantitative analysis, but it is a time-consuming task if done manually. The authors constructed positron emission tomography (PET) and computed tomography (CT) atlases from 275 whole-body PSMA PET/CT scans and proposed an unsupervised machine learning strategy for organ segmentation, incorporating the atlas-based image registration. They proposed this as a method to alleviate the need for an annotated training data set and yet still provide fast and reliable segmentation results that are similar to those results achieved from methods trained with an accurately annotated data set.

Hohberg and colleagues studied the absorbed dose of ¹⁷⁷Lu-PSMA-I&T, another PSMA-targeted RLT that is still in phase 3 trials, in bone vs lymphatic metastases in patients with metastatic castration-resistant prostate cancer (mCRPC; poster P970). They also looked for changes in the mean dose over treatment cycles and potential relationships to response status. Additionally, the authors were interested in the ability of pretreatment PSMA PET/CT scans to predict treatment response.

While researchers work toward the goal of personalized PSMA-targeted RLT, it is notable that currently available therapy, with its standard approved dosing schedule, can improve QOL in heavily pretreated patients with mCRPC. Prior to the SNMMI conference, Fizazi et al reported additional HRQOL data from the phase 3 VISION trial, showing that ¹⁷⁷Lu-PSMA-617 plus standard of care delayed time to worsening in HRQOL and time to symptomatic skeletal events compared with standard of care alone. Thus, ¹⁷⁷Lu-PSMA-617 is among the growing list of modern agents for mCRPC that have been shown to improve QOL outcomes. 

Highlight Article: Quality of Life and Treatment Personalization in Advanced Prostate Cancer

Overview
In metastatic castration-resistant prostate cancer (mCRPC), effective disease control is key to preserving quality of life (QOL). Additionally, with multiple life-prolonging options available, there is room to personalize therapy for patients with mCRPC.

First and foremost, the effective treatment of the cancer itself is key to maintaining patients’ QOL. This may be underappreciated initially, so we must really engage patients and their families in seeing both the risks and the benefits of proposed treatments. There are definitely patients who present with significant fatigue and weight loss due to the cancer, but, after starting effective treatment, they can regain energy and weight and feel their QOL improve. Specifically in prostate cancer, controlling the cancer helps to preserve mobility by avoiding bone pain and reducing the frequency of skeletal-related events such as pathological fracture and spinal cord compression. A variety of studies document QOL improvements with contemporary treatments for mCRPC, and it is very important to help patients and their families see the upside of the treatments.

Of course, we also discuss the potential side effects of treatment, which can negatively impact QOL. Patients with prostate cancer may be struggling with sexual side effects and with issues related to body changes from hormone therapy, and when they transition to castration-resistant disease, they face lifelong, ongoing hormone therapy. They are "in it for the long haul" at this point, and it is really important that we engage with them to understand their QOL concerns and that we offer whatever remedies that are available, including explaining the potential benefits of diet and exercise modifications in the maintenance of overall health.

The factors that influence QOL are numerous and go beyond the side effects of the different treatments that we use in mCRPC. However, we can consider these side-effect profiles in our discussions with patients. Now that we have more treatment options for mCRPC, it is becoming possible to discuss them from the standpoint of how well each will fit into the patient's lifestyle and what each treatment entails. For example, we can explain that if we wanted to go with the recently US Food and Drug Administration–approved lutetium Lu 177 vipivotide tetraxetan instead of moving to cabazitaxel, the patient would be able to come in less frequently and the treatment would be less likely to cause certain side effects, such as severe diarrhea.

Often, we lack head-to-head data that would further guide our selection and/or sequencing of therapies. For instance, in a patient with mCRPC who qualifies for a poly (ADP-ribose) polymerase inhibitor, we do not necessarily know whether that treatment should be given preferentially to chemotherapy. However, even now, there is some room for personalization. In a patient who is progressing rapidly and is very symptomatic, we might consider chemotherapy; it may, in fact, be easier for such a patient to understand that chemotherapy is going to help them. For someone with slower, asymptomatic, prostate-specific antigen–only progression, perhaps a nonchemotherapy option would make sense. Thus, the process involves considering all of the options to determine which might be right for the individual patient at hand, at that particular moment in time, and acknowledging that we will try to use all available options regardless of sequence.