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Prostate Cancer Personalized Therapy

CE / CME

Expert Think Tank on Applying the Latest Data to Individualize Treatment in Prostate Cancer

Pharmacists: 1.00 contact hour (0.1 CEUs)

Nurses: 1.00 Nursing contact hour

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit™

Released: August 16, 2023

Expiration: August 15, 2024

Tanya B. Dorff
Tanya B. Dorff, MD
Rana R. McKay
Rana R. McKay, MD
Alicia Morgans
Alicia Morgans, MD, MPH
Michael Schweizer
Michael Schweizer, MD
David VanderWeele
David VanderWeele, MD, PhD
CME/CE Information

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Case Study: nmCRPC

To frame this conversation, we will consider the following patient with high-risk nmCRPC. The patient is 74 years of age, 2 years removed from prostatectomy with conventional bone scan, CT negative, and has a PSA of 2.1 ng/mL with a doubling time of 4 months while on ADT. What is your next move?

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SPARTAN, PROSPER, and ARAMIS: OS (Secondary Endpoint)

Rana R. McKay, MD:
The nmCRPC entity is ever shrinking because we are finding these people to actually have metastases detected on PET imaging. The clinical trials supporting the 3 approved ARSIs (apalutamide, enzalutamide, darolutamide) for treating nmCRPC showed prolongation of MFS and OS despite being conducted before the PSMA PET imaging era. For individuals who have high risk nmCRPC, I think about escalating with an ARSI. Patients with nmCRPC with a long PSA doubling time were not included on these trials and ADT alone remains an SoC for these individuals.  

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PSMA PET Imaging in nmCRPC

Alicia K. Morgans, MD, MPH:
Would you perform a PSMA PET scan in this setting? And if you found something, would you act on it?

Michael T. Schweizer, MD:
The PET scan does not add much in the setting of nmCRPC as defined by conventional imaging because the SoC has been ADT with either apalutamide, enzalutamide, or darolutamide and I would not anticipate doing something else in this setting even if PET imaging showed low-volume metastatic disease. The areas I usually get a PSMA PET scan are either for upfront staging if I am worried about high risk for distant metastases and I want to think about treating everything; or in patients who have biochemical recurrence and I am thinking about MDT. After that, I also use it for patients I am evaluating for Lu-177-PSMA-617 therapy, which we will discuss later.

David VanderWeele, MD, PhD:
I generally agree. I have used PET imaging for patients with nmCRPC, although by that point, much of the time I have already obtained a PET scan that demonstrated metastatic disease or disease that was not amenable to radiation, such as recurrence in the pelvis after salvage radiation. In that case, I do not bother with the PET. More often I find that there is a higher burden of disease than I would have previously expected. In some scenarios if I think there is a chance there might be only 1 or 2 metastatic sites, I might consider MDT, even though there is limited data to support it.

Alicia K. Morgans, MD, MPH:
I would say the tried-and-true situations to use a PET scan are the ones that Dr. Schweizer mentioned, and I always use them in those settings. To Dr. VanderWeele’s point, I have sometimes used PET imaging in nmCRPC, and followed by MDT. I have given radiation based on conventional imaging mCRPC in the past, but I have never seen that change the trajectory of disease in a meaningful way.

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Prognostic Value of PSMA PET

Tanya B. Dorff, MD:
One thing I thought was new and interesting in the nmCRPC setting at the American Society of Clinical Oncology 2023 Annual Meeting was the prognostication value of PSMA PET. We have acknowledged that we do not yet know how to treat patients based on PSMA PET because all studies to date have been based on conventional imaging. However, not only was the amount of disease (≥5 vs <5 locations) shown to be prognostic, but so was the intensity of PSMA uptake.26 It really speaks to the fact that we eventually will be using PSMA PET to categorize patients, and future trials really will need to include PSMA PET.

Rana R. McKay, MD:
I would add that currently, all of our response and progression criteria are based on conventional imaging and bone scans, and we know how crude bone scans can be. I think we need to integrate PSMA PET into as many clinical trials as we can and take those data and analyze them in the context of what is happening with conventional imaging, to define these new benchmarks for the future. As we integrate this tool clinically, we are going to need to better understand what progression actually looks like. Is it just increased intensity in existing lesions? Is it new lesions? How many new lesions? Where are the lesions located? With other sorts of imaging modalities, certainly CT and bone scan, when people have widespread bony metastases there has been evidence of documented flare on imaging. I do not know whether that has been fully characterized for PSMA PET. 

Tanya B. Dorff, MD:
We have to remember that the PSMA PET, for now, may not be telling us the complete story in every patient. We should keep in mind that there is a percentage of patients whose disease is not detectable by PSMA PET. In the phase III VISION trial, 12.6% (126 of 1003 scanned) of patients had no PSMA-positive lesions, or ≥1 exclusionary PSMA-negative lesion.27 I think PSMA PET has to be embedded together with conventional imaging. Some places are also doing fluorodeoxyglucose (FDG) PET, which may be a lot to ask in community practice when access to PSMA PET can already be challenging. 

Rana R. McKay, MD:
Yes, and I think that is particularly true in later stage CRPC where the disease is much more heterogeneous and may not be as driven by the AR pathway.

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