New Technology Advances Prostate Cancer Care But Questions Linger

Incorporating new technology such as prostate-specific membrane antigen (PSMA) PET scans will help propel prostate cancer care forward, improving outcomes for patients, but many questions remain on the best dosing regimens as well as treatments for patients, according to Phillip J. Koo, MD. Physicians should continue to encompass all aspects of care into decision making in addition to considering clinical trial data as a clear consensus is not apparent in many areas of care.

“There is clear agreement and consensus that PSMA PET is the best imaging technology, and it will slowly replace bone scans and computerized tomography [CT] scans,” Koo said. “The fact that it detects disease better, it’s more accurate, it’s more sensitive, and more specific in our patients and various disease states, is undeniable. There’s no disagreement there. It’s that next step with regard to what you do with that information.”

Koo, the cochair of the Inaugural Prostate Cancer Conference, hosted by OncLive^®, discussed the top takeaways from the meeting, which took place on February 18, 2023.

“Thinking back to the meeting, there were definitely some areas where everyone could generally agree on certain philosophies, but what we also realize is there are even more areas where it [can be] hard, even amongst a group of experts, to agree on uncertain management or treatment pathways,” Koo said.

In an interview with OncLive^®, Koo, the division chief of Diagnostic Imaging and Northwest region oncology physician executive at Banner MD Anderson Cancer Center in Phoenix, Arizona, highlighted insights garnered from the collective experts on topics such as radioligands and modern radiopharmaceuticals, which, along with artificial intelligence (AI), have the potential to revolutionize the field.

OncLive^®: Which sessions from the Inaugural Prostate Cancer Conference do you think were the most important discussions?

Koo: I’m a little biased—I’ll say that the theranostics session was most interesting. We had an amazing group of thought leaders, experts in the field, multidisciplinary [as well]. We had A. Oliver Sartor, MD; Michael J. Morris, MD; Scott T. Tagawa, MD, MS, FACP; [and] Andrei Iagaru, MD. [There were] wonderful discussions about dosing, and a lot of times when these new radiopharmaceuticals gain approval, it’s with the goal of getting a label, but now that we have a label, [these agents are] challenging the whole field to think about better ways to get the right dose to the right patients.

Right now, with lutetium (177Lu) vipivotide tetraxetan [Pluvicto] we’re [administering] 200 mCi [for] up to 6 doses. In reality, that’s probably not the optimal dose and from this point moving forward, we need to design more clinical trials looking at whether we should dose higher in the beginning and decrease that dose, whether we look at dosimetry, [and] whether we look at if [an individual] is responding well, maybe 2 or 4 doses is enough, rather than 6. All these questions are very important, because they are going to lay the groundwork for future trials and future questions [such as] can we retreat patients with lutetium vipivotide tetraxetan?

Is there a particular session that you found interesting?

It was such a wonderful meeting. We started off [with] high-risk disease, biochemical recurrence, oligometastatic disease, metastatic hormone-sensitive [disease], metastatic castration-resistant [disease], [and then] PARP inhibitors. We covered every single topic in advanced prostate cancer.

An interesting area is the upfront space, high-risk disease in the biochemically recurrent space, is there anything that we can do in that patient population that might lead to more durable responses or potentially a cure? [There are] a lot of discussions about oligometastatic disease, [but we] still we don’t have that clear level 1 evidence on metastasis-directed therapy, and it’s clearly a hot topic. [There are] a lot of great trials [that are] going to help answer those questions, but it still leaves a lot of physicians out there struggling with what to do in those situations.

Another complicating factor is PSMA PET [scans]. It is absolutely wonderful that we now have much more availability for this wonderful tool. The reality is it’s created a lot of questions and a lot of clinical scenarios for physicians [for which] we don’t have clear answers. One of the goals of this meeting was to provide that type of guidance for the community practitioner with regard to how best to manage patients given the lack of clear level 1 data. With PSMA PET, [there are] a lot of great discussions about this, about when to use it, [and] how to interpret the results. Unfortunately, I don’t think there’s always a clear black and white answer. We’ll do our best to collate this information and come up with some recommendations, but in the end, it’s going to be guidance and the practitioners are going to need to figure out what works best for them, their patients, and their practice.

If there is a consensus, what kind is it and what does it mean for clinical practice? What do you think the significance of this meeting is?

At minimum, what we’re able to do is identify areas in the management of patients with prostate cancer—from high-risk disease to metastatic castration-resistant disease—[and provide] some guidance on what this multidisciplinary group of experts agree on, and certain topics where is there clear disagreement or lack of agreement. [With] that lack of agreement, then we’ll dive deeper into what were the issues to think about.

We have end points and clinical trials [data], and that was a very big discussion, but what does that mean? How do we take into account these end points plus other factors such as quality of life, patient-reported outcomes, performance status, all these other factors that come into play in real life when you’re managing patients. That’s where we hope to shed some light on those areas that need to be considered to help everyone make those appropriate decisions and we’re also hoping to provide some light on where we go from here.

As we design more clinical trials, we need to be more thoughtful about end points; there were some lively discussions amongst this group of experts with regards to how best to accomplish that in the future.

What are some of those areas at this point you think might have clear consensus and what are some of those areas where there’s still a lot of disagreement?

From my area of expertise with imaging, PSMA PET is no longer next-generation imaging…. It is the best imaging tool and it’s something that we need to continue to incorporate. It’s wonderful to see that many new trials are being designed incorporate PSMA PET into protocols. That’s a great step forward.

Another area that’s exciting is radiopharmaceuticals therapies. Radioligand therapies are here to stay. We are seeing more trials in development that are going to change how they’re used and in [which] disease states. We have PSMAfore [NCT04689828] which has been reported out as positive.¹ Hopefully we’ll see those results perhaps at the American Society of Clinical Oncology Meeting [(ASCO) Annual Meeting], that’s going to be groundbreaking and it’s going to change how we approach these patients. There’s clear consensus that, yes, radiopharmaceuticals, radioligand therapies are game changing [and] we need to incorporate them into our practices. But we also need to continue pushing that envelope and continuing that journey to discover which patients it works best in.

That’s one of the themes that has emerged—we have all these great drugs now we need to identify the subset of patients and embrace personalized medicine to figure out who benefits from which therapy at what time.

Are there any research efforts that you are involved in that you want to highlight?

One area that we need to dive into is radiomics. Right now, imaging in clinical trials is used to assess response and we often use morphology and size using RECIST 1.1 [criteria]. There’s so much more available with imaging, more data that we can access and using AI tools. If we access those tools and correlate that with clinical data, I have no doubt we’ll be able to generate more robust prognostic [and] predictive tools to help us manage our patients better.

At the ASCO Genitourinary Cancers Symposium we had a great presentation from Daniel E. Spratt, MD, who talked about the MMAI [model]² with pathology and it’s an area that everyone is excited about. [AI is] another topic that came up multiple time. AI in medicine and in oncology is here to stay; it is what’s going to help us take that next step to more robust and better care for patients.

I’m currently working on a few projects to get access to some of these datasets to see where those connections lie. One of the challenges is access to that data; it’s not as easy and available as we would like.

References

1. Novartis Pluvicto shows statistically significant and clinically meaningful radiographic progression-free survival benefit in patients with PSMA–positive metastatic castration-resistant prostate cancer. News release. Novartis. December 5, 2022. Accessed February 21, 2023. https://www.novartis.com/news/media-releases/
2. Spratt DE, Liu VTY, Yamashita R, et al. Patient-level data meta-analysis of a multi-modal artificial intelligence (MMAI) prognostic biomarker in high-risk prostate cancer: results from six NRG/RTOG phase III randomized trials. J Clin Oncol. 2023;41(suppl 6):299. doi:10.1200/JCO.2023.41.6_suppl.299