Filling the Gap: Creating a Specialized PRO Measure for Radionuclide Therapy in Prostate Cancer, Journal Club - Zachary Klaassen & Rashid Sayyid

June 20, 2023

Rashid Sayyid and Zach Klaassen a paper on the development of a patient-reported outcomes (PROs) measure for radionuclide therapy for prostate cancer, published in the Journal of Nuclear Medicine. They explain the importance of PROs in evaluating the impact of these emerging oncology treatments on patients' quality of life. Highlighting a current gap in the literature, they note that existing PRO measures are not specifically tailored for radionuclide therapy. The authors of the study developed a specialized questionnaire called the FACT-RNT. The development process was systematic, involving a broad review of radionuclide therapy-related symptoms, input from international experts, and evaluation by patients. The speakers conclude by emphasizing the need for further validation of the FACT-RNT measure, particularly in diverse patient populations. They note the importance of its application in clinical trials and real-world settings to better understand and improve the impact of radionuclide therapies on patient quality of life.


Rashid Sayyid, MD, MSc, Urologic Oncology Fellow, Division of Urology, University of Toronto, Toronto, Ontario

Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Georgia Cancer Center

Read the Full Video Transcript

Rashid Sayyid: Hello everyone. This is Rashid Sayyid. I'm a urologic oncology fellow at the University of Toronto, and along with Zach Klaassen, associate professor and program director at Augusta University, we'll be discussing the recent publication from JNM that looked at developing a patient reported outcome measure for radionuclide therapy for prostate cancer. This study was recently published on May the fourth in the Journal of Nuclear Medicine.

Radionuclide therapy is an emergent class of oncology agents in the mCRPC space. Currently, we have two radionuclide therapy agents FDA approved in this space. We have radium-223 that was approved in 2013, and we also have 177-lutetium-PSMA-617 that was approved in 2022 on the basis of two studies, the TheraP trial that looked at this lutetium agent versus cabazi after prior dosing, and an androgen receptor signaling inhibitor, and was shown to improve biochemical response rate with an improved toxicity profile, albeit with no comparative overall survival benefit. Also, we had the VISION trial that looked at lutetium versus standard of care after prior docetaxel and ARSI, and again, this study was a positive one with lutetium improving RPFS and OS compared to standard of care in this setting.

Patient reported outcomes are critical to assessing treatment tolerability and patient reported toxicities. Even though these studies have demonstrated potential oncologic benefits, it's important to understand the effect of these drugs on the patients' quality of life. Patient reported outcomes or PROs for short are often under-reported in clinical studies, and as such, in order to improve adherence to this in reporting, the FDA currently encourages patient reported outcomes as a trial primary endpoint or as a complement to clinical and physiologic endpoints, and patient reported outcomes have been shown to be closely associated with clinical outcomes. It has been shown superior health related quality of life or PROs among patients with improved biochemical response to lutetium, and also, radionuclide therapy response to lutetium or actinium is associated with PRO improvement. We see based on these results that there is consistency between clinical endpoint improvements and patient reported outcomes from patients.

Currently available patient reported outcome measures, example, the ERTC quality of life questionnaire and the FACT-P, are quite lengthy and also designed to assess the impact of conventional therapies such as chemotherapy and radiotherapy, and not radionuclide therapy specifically. As such, there's a limitation in the current literature, and so a brief targeted patient reported outcome measure specific for radionuclide therapy is needed to optimize the patient reported outcome measurement, to assess the prognostic value of patient reported outcomes, and also to allow for cross-trial comparison and reporting of radionuclide therapy associated patient reported outcomes.

To this end, the authors developed the FACT-RNT, and FACT stands for the functional assessment of cancer therapy, and they developed this between 2021 and 2022 at UCLA and the Moffitt Cancer Center. This was quite simple actually. It was developed in four steps. We see in the flow diagram here to the right the different steps, and we'll go through them one by one. They're quite simple, so starting off with the first step, the authors compiled a broad comprehensive list of RNT symptoms and toxicities by reviewing the published literature and by performing a semi-structured interview with 29 patients, 14 caregivers, and 11 clinicians. They cast a wide net to start, identifying all possible radionuclide therapy related symptoms and toxicities. Next, the symptoms and toxicities that were identified in the first step were cross-referenced with the Functional Assessment of Chronic Illness Therapy item library. Essentially what they did, they took that broad net and they filtered out the ones that were not in the library and only kept the ones that were cross-referenced with the library.

Again, now we get a bit more specific. The third step was that internationally renowned experts in the field of radionuclide therapy and patient reported outcomes were interviewed to seek the consensus on which symptoms and toxicities were relevant to the radionuclide therapy. As such, this was filtered even further to include only those ones that are likely specific to radionuclide therapy. This was the first draft of the FACT-RNT or the functional assessment of cancer therapy in radionuclide therapy. As a fourth step, the final step, 11 patients from the first step reviewed this draft and then participated in semi-structured interviews to assess the measure for its acceptability, for its comprehensibility, whether it's relevant to radionuclide therapy, and also assess the self-efficacy for completing the measure. After this draft was reviewed by the 11 patients, this was considered the final draft of the FACT-RNT, and this was the questionnaire that was used.

At this point, I'll turn it over to Zach to go over the results and discussion of this paper.

Zach Klaassen: Thanks so much, Rashid, for laying out how this was developed. This is basically the table looking at characteristics of those that were interviewed, including the recipients, the caregivers, and the clinicians. We'll walk through each of these columns in turn. As Rashid mentioned, for step one, there was interviews that were conducted for the recipients, which included 29 patients, 14 caregivers, and 11 clinicians. When we look at these 29 recipients, we see that the median age was 72 years. Of course, all of these patients were male. 90% of these were non-Hispanic. 83% of these patients were white, and as Rashid mentioned, there was a long latency between diagnosis and receipt of radionuclide therapy, and this was 11.7 years for these patients, and these patients received four injections of radionuclide therapy.

When we look at these caregivers, the median age was 64. These were all females. 93% were non-Hispanic, 79% were white, 14% were Asian. When we look at the clinicians, median age of 56 years, 64% were male, 73% were non-Hispanic, 55% were white, 18% were Asian. Then, fast-forward to step four, this is when the recipients were then re-queried. We see that the median age was 71. Again, all male, 82% non-Hispanic, 73% white. Median of 4.45 injections and a median 11.84 years since diagnosis.

This is essentially the final FACT radionuclide therapy items, so if we look at these in detail, there's very specific questions, and the response options range from one, not at all, or five, very much, so very, very simple. Essentially a Likert score measurement for each of these questions, so, "My mouth is dry," "My eyes are dry," "I have difficulty urinating," "I have nausea," "I have been vomiting," "I have diarrhea," "I am constipated," "I have loss of appetite," "I feel fatigued," "My fatigue keeps me from doing things I want to," "I'm bothered by side effects of treatment," and, "I feel isolated from others because of my illness or treatment."
Specifically, they had several questions identifying pain, and some of the discussion in putting this together was how to have different pain questions, which may be different based on location. The first pain question was, "I have bone pain." The second one was very general, is, "I have pain," and the third one was, "My pain keeps me from doing things I want to do." Again, these were highlighted by responses from one to five, and you can see here that the FACT-RNT is available at the website listed here.

The FACT-RNT for prostate cancer addresses the current gap in measuring RNT specific symptoms and toxicities, and responds to FDA guidance on implementing patient reported outcomes in therapeutic trials and real-world settings to identify prostate cancer patients at risk for deterioration. The FACT-RNT was designed for use and future adaptation with a broad variety of RNT agents with different molecular targeting mechanisms and radioisotopes. Finally, the sample was primarily non-Hispanic white men. Thus, future studies should validate the FACT-RNT in large, diverse, prostate cancer samples.

In conclusion, the study represented the FACT-RNT for prostate cancer, a new measure developed through multi-step collaboration with patients, caregivers, clinicians, and international experts. The next steps include assessment of internal consistency, validity, and reliability, and use in radionuclide therapy clinical trials and real-world settings. We thank you very much for your attention. We hope you enjoyed this UroToday Journal Club discussion.