Overview of Metastatic HSPC: Diagnosis and Risk Stratification

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EP: 1.Overview of Metastatic HSPC: Diagnosis and Risk Stratification

EP: 2.Systemic Treatment Armamentarium in Metastatic HSPC

EP: 3.What is the Role of Locoregional Therapy in Metastatic HSPC?

EP: 4.Informing Systemic Therapy Selection With Negative Data in HSPC

EP: 5.Evolving Treatment Landscape of Nonmetastatic Castration-Resistant Prostate Cancer

EP: 6.Advent of PARP Inhibitors in Metastatic CRPC

EP: 7.Combination PARPi Strategies in Metastatic CRPC: Interpreting Data From Clinical Trials

EP: 8.Radioligands in the Treatment of Metastatic CRPC: Lutetium-177–PSMA-617

EP: 9.Radioligands in the Treatment of Metastatic CRPC: Radium-223

EP: 10.Metastatic CRPC: Novel Treatment Strategies With Radioligand Therapy

EP: 11.Novel Therapeutic Targets in Metastatic CRPC

EP: 12.Potential for CDK4/6 Inhibitors in Metastatic CRPC

EP: 13.Ongoing Clinical Trials in the Metastatic CRPC Setting

EP: 14.CAR T-Cell Therapy in Metastatic CRPC and Future Directions in Care

Transcript:

Rana McKay, MD:Hello, and welcome to this Onclive® Peer Exchange Updates and Treatment Approaches for Prostate Cancer. I am Dr Rana McKay and I’m a GU [genitourinary] medical oncologist at the University of California in San Diego. Joining me today in this discussion are my colleagues. Please introduce yourself.

Arash Rezazadeh Kalebasty, MD:Yes. [I’m] Arash Rezazadeh. I’m a GU medical oncologist currently at the University of California, Irvine.

Rana McKay, MD:Sumit Subudhi.

Sumit K. Subudhi, MD, PhD:I’m a medical oncologist at [The] University of Texas MD Anderson Cancer Center.

Rana McKay, MD:Dr Scott Tagawa.

Scott Tagawa, MD, MS, FACP:Hi, I’m Scott Tagawa. I’m at Weill Cornell Medicine, NewYork-Presbyterian Hospital.

Rana McKay, MD:Dr Ulka Vaishampayan.

Ulka Vaishampayan MD:Hi, I’m Ulka Vaishampayan. I’m at [the] University of Michigan, [and am a] GU medical oncologist.

Rana McKay, MD:Today we’re going to discuss several topics, specifically the most recent updates for prostate cancer. We’ll discuss the latest research in the field and the impact of recent clinical trials on making decisions around treatment selection. Thank you all for joining me today. We’re going to start out our discussion talking about the evolving treatment landscape in metastatic hormone-sensitive prostate cancer [mHSPC]. Maybe we can start with how do you approach metastatic HSPC? How do you approach treatment selection? How do you approach risk stratification?

Sumit K. Subudhi, MD, PhD:I guess I’ll start with that. The first thing I look at is the disease burden and whether they have high-volume versus low-volume [disease] as per the charted criteria. In addition, look at comorbidities that the patients may have and medications because there is a lot of cross-reactivity with a drug-drug interaction with patients’ home medications with some of the second-generation hormones that we may want to combine with their therapies.

Rana McKay, MD:That’s great. Others, what do you all think? Do you use genomic profiling at all? What kind of factors go into your decision-making around therapy selection for mHSPC?

Ulka Vaishampayan, MD:Yeah. I think definitely look at the life expectancy of the patient because that is going to factor into a number of treatment decisions. To Sumit’s point, the comorbidities also factor in. I think there is a discussion involved about doing genomic testing and at the minimum germline testing potentially somatic testing also at that point. Knowing that we may not apply that until castrate resistance stage, it is still better to do that earlier the better.

Rana McKay, MD:Scott, what do you think about integrating PSMA PET [prostate-specific membrane antigen positron emission tomography] into your risk stratification? We’ve heard a lot of discussion around that. Do you use that to determine high-/low-volume? What do you think about that?

Scott Tagawa, MD, MS, FACP:I’d say fairly clearly, I’m a little biased in terms of PSMA but fairly clearly PSMA imaging technology is one of the biggest disruptors that we have in the field. It’s really opened our eyes in certain ways, but also made it very confusing. Some of our patients will have an initial workup finding on PSMA PET but have not had any other imaging [and it] is unclear what volume status means with that. And sometimes they will go back and do a bone scan and/or CT scan to clarify things. If for no other reason, then I’m probably also going to follow them with a bone scan or a CT or MRI. I want to have a baseline that’s there. Generally speaking, I expect them to have a higher number of metastasis [mets] on a PSMA PET than the other modalities. That also helps re-stratify. If they have a million mets on a PSMA PET, that probably means visceral disease. Then they’re probably going to fall in the high-volume category. But it’s a difficult decision.

Rana McKay, MD:Yeah. I hear you. It’s challenging because we’re trying to make decisions for our patients in the clinic but our definitions of what defines high- and low-volume [disease] are really predicated on conventional imaging. So to apply PSMA PET imaging, we’re not totally there right now at the present time. Do you all actually [use] risk stratification? We’ve heard from charted about low- and high-volume matters. We’ve heard from charts about the timing of metastatic disease matters, whether it’s synchronous or metachronous. And do you all utilize that kind of risk algorithms if you will in the clinic?

Arash Rezazadeh Kalebasty, MD:Yeah, I do. I actually look at de novo metastatic disease in different categories of disease. They’re normally much more aggressive. Unfortunately, we don’t have a lot of biomarkers to know how people are going to do. So we use clinical assessments like de novo metastatic disease, the volume of disease. Maybe liver disease is a different animal, is a little bit different. We call it a visceral disease. On our PSMA scans now, just want to bring it up here. I see peritoneal involvement nowadays that [we] didn’t use to see with CT scans. It was missed, or maybe wasn’t looked at as it could be that. But it sounds like those lesions respond very well to treatment compared to other situations that really peritoneal mets are bad. In my practice, I’ve seen good results. But there’s a lot to learn actually. What [does] the disease volume mean? We have that arbitrary categorization of low versus high volume. Yes, but I think patient comorbidity and life expectancy to your point, it’s very important to incorporate docetaxel or not.

Rana McKay, MD:Yeah. I think the de novo setting is a really excellent opportunity for integrating care with urologists, especially people presenting with a bulky primary. They may need procedures to kind of resolve urinary retention or other issues. How do you all collaborate with your urologist at your institutions, especially in the HSPC setting?

Ulka Vaishampayan, MD:I think the de novo state, usually when they present, they’re frequently symptomatic. They haven’t presented just with an elevated PSA [prostate-specific antigen] for the most part. So there is a lot of chaos around the diagnosis. If they have bone pain or if they have neuropathic compression, then of course there are other specialties involved. Specifically with urology, I typically tend to, even with the elevated PSA, I tend to have urology involvement to do the biopsy. So we get tissue on the patient, a tissue diagnosis, which of course has multiple prognostic and characteristics, next-gen [next-generation] sequencing, etc., down the road. I think consideration of local therapy may be for obstruction, if they need catheter suprapubic, etc. for long-term management those things come into play. But for the most part, you know that you’re going to start systemic therapy, chances are pretty soon you’re going to get a response and a clinical improvement of symptoms.

Rana McKay, MD:Very exciting. Very good. It’s becoming an ever more multidisciplinary disease with integrative care with urology, integrative care with radiation oncology. We’re going to talk about it a little bit later, the role of radiation therapy to the primary role of radiation therapy to mets. It’s becoming ever more dynamic. As we think about risk stratification in the mHSPC setting, we saw some interesting data getting presented at ESMO [European Society for Medical Oncology meeting] about the utilization of Decipher and other sort of algorithms for risk stratifying. Do you think we’re there yet? Do you think those assays are ready for prime time or not quite yet?

Arash Rezazadeh Kalebasty, MD:I think that’s the key. Right now, we just have to look. And look, every time we do a trial, we have to look at these markers because one day we’re getting there, but not quite there. We have to treat each patient differently based on their genetic profile, I think so. So we still categorize these patients in 3 buckets, and 4 buckets, and try to apply the treatments to them. But as we do … it’s good to have that exploratory end point to look at who responds, who doesn’t respond, why they respond, or why they don’t. We are not there in my opinion, but we are doing things together.

Rana McKay, MD:Yeah, very good point. We don’t have any biomarker selection strategies for mHSPC, but hopefully kind of the next wave of studies to be conducted will help better inform that.

Transcript edited for clarity.