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High-Risk Prostate Cancer: Diagnosis & Treatment Strategies

Author Javier Prieto III covers High-Risk Prostate Cancer: Diagnosis & Treatment Strategies on BackTable Urology

Javier Prieto III • Mar 7, 2024 • 40 hits

Radical therapy remains the cornerstone in the treatment of high-risk prostate cancer, encompassing modalities such as radical prostatectomy and brachytherapy. Criteria for high-risk designation typically include a Gleason score ranging from 8 to 10, grade 4 or 5, or PSA levels surpassing 20.

The collaboration between UC San Diego urologic oncologist Dr. Aditya Bagrodia and Case Western University radiation oncologist Dr. Daniel Spratt, featured on the BackTable Urology Podcast, sheds light on patient evaluation workflows, imaging techniques, and approaches to radiation therapy in high-risk prostate cancer. The doctors also underscore the critical role of PSMA PET scans in detecting metastases, offering superior diagnostic capabilities compared to conventional imaging modalities.

This article features excerpts from the BackTable Urology Podcast. We’ve provided the highlight reel here and you can listen to the full podcast below.

The BackTable Urology Brief

• Radical therapy for high-risk prostate cancer involves detailed patient evaluation, including symptom questionnaires and consideration of GI history. Challenges arise from conditions like GI disorders and comorbidities, underscoring the importance of personalized treatment strategies, including genetic testing.

• After an extensive assessment, high-risk prostate cancer patients undergo diagnostic tests like MRI and PSMA PET scans for staging and metastasis detection. Standardized reporting systems such as PSMA-RADS and MRADS ensure consistent interpretation and communication among healthcare providers.

• Physicians should meticulously assess lymph nodes and seminal vesicles when treating prostate cancer due to metastasis risks. While full-dose radiation to seminal vesicles is standard, the decision to irradiate lymph nodes is selective and typically influenced by cancer recurrence and patient quality of life.

High-Risk Prostate Cancer: Diagnosis & Treatment Strategies

Table of Contents

(1) Comprehensive Evaluation of the High-Risk Prostate Cancer Patient

(2) Standardized Diagnostics in High-Risk Prostate Cancer

(3) Radiation Therapy in High-Risk Prostate Cancer: When to Target the Lymph Nodes

Comprehensive Evaluation of the High-Risk Prostate Cancer Patient

Radical therapy represents a vigorous approach to treating high-risk prostate cancer, demanding thorough patient evaluation to identify potential contraindications. Initial steps often involve assessment tools like the International Prostate Symptom Score (IPSS) questionnaire or the American Urological Association Symptom Index, which is crucial for understanding disease progression. While not obligatory for prostate cancer cases, assessing gastrointestinal (GI) history becomes essential for patients with conditions such as Crohn's disease and ulcerative colitis, which may exacerbate treatment-related complications.


Despite advancements like rectal spacers and precise radiation therapy, the inflammatory nature of these GI disorders can introduce unforeseen challenges. Additionally, comorbidities like obesity, heart disease, diabetes, and metabolic syndrome may necessitate tailored treatment regimens to combat high-risk prostate cancer effectively. Furthermore, genetic testing is often recommended for high-risk patients with a positive family history of prostate cancer, as identifying mutations such as BRCA1 can offer invaluable insights into treatment strategies.

[Dr. Aditya Bagrodia]
Today, we're going to round things out with high-risk prostate cancer. Absolutely a pleasure. I thought it might just be helpful to get some basic definitions in there. High-risk, very high-risk when patients are coming to you. Who are we talking about here?

[Dr. Daniel Spratt]
I would say defining high-risk is a little easier as a larger bucket. We're talking to high grades of Gleason 8 to 10, or Grade group 4 or 5, PSAs over 20. Now, it's probably more in the MRI realm, but clinical T3, rarely we see these T4 patients. I think the value of very high-risk, and the definition used in NCCN is highly debatable. That's from a retrospective study, I think out of Hopkins that I don't think has a lot of clinical implications, and most of the guidelines say you treat them the same. There's been some newer definitions. People call the STAMPEDE very high-risk, which is PSAs over 40, high-grade T3, having two or more of those features, which may have some actual clinical implications.

[Dr. Aditya Bagrodia]
Totally. We'll definitely jump on into it, the primary pattern 5, the T4, things along those lines. Essentially, high PSAs, Grade group 4 and above, radiographic, something's at least got your attention, that's who we're talking about.

[Dr. Aditya Bagrodia]
Starting with patient intake, what are the critical elements here as you're starting to formulate what might be a best option for this patient? Maybe we could start with urinary symptoms, sexual health, things along those lines?

[Dr. Daniel Spratt]
I think probably for almost any man that you're potentially going to give a radical therapy to, we're going to want to know whether it's the AUA or IPSS, some type of irritative obstructive-type symptom assessment or an epic 26. Any rectal bowel movement, history challenges, Crohn's, ulcerative colitis, things of that nature, erectile function, of course. Even beyond that, I think it's also what's the priority for the patient. Some guys may have function, but it's just not a big priority depending on the significant other. Comorbid conditions, obesity, metabolic syndrome diabetes, heart disease. There's social factors, of course, to factor in also when talking about feasibility of treatment, where to get it, things like that.

[Dr. Aditya Bagrodia]
I think that priority element is actually quite important. I do mean it, but I almost have found that I tell every patient when they describe their sexual frequency patterns, I'll say, "That's totally normal," because I don't want people to feel weird about being sexually inactive or being sexually active at whatever frequency, whether or not they're able to have erections and so on and so forth. GI history, that's probably something that I don't think that urologists focus on, maybe quite as much. Ulcerative colitis, Crohn's disease, colonoscopies. Is this all mandatory intake?

[Dr. Daniel Spratt]
I would say so. It's been ingrained in me back in my training in New York at Sloan Kettering. I remember Michael Zelefsky telling me that every, we'll call it five years of his career, he's like, "Oh, maybe we'll try to do some radiation on this guy with Crohn's." Then he's like, "I learned my lesson again." While there's definitely cases I've done, especially now with the rectal spacers, and the accuracy of radiation, that's something that I would say, if it's active, even if it's a history, there's got to be a reason why we're starting with radiation therapy because that could be potentially catastrophic. We're talking fistulas, we're talking a lot of things. It's a little more complicated in high-risk. If it's ultra high-risk, and you know you have surgery, you may need post-op radiation at some point. Those are even larger fields. It's a conversation with the patient for sure.

[Dr. Aditya Bagrodia]
Obviously, we're talking about relatively infrequent cases, lower probability events, but they do pop up. By all means, if there's a patient, I think, from our end on the urology side that we know is going to be inclined towards radiation, getting that history, and getting a colonoscopy set up, I think is something we can do. Then you mentioned cardiac history. Obviously, that's going to have an impact on androgen deprivation therapy, and maybe which types of medications they would be best suited for. Family history, is this something that you're really dialing in on?

[Dr. Daniel Spratt]
We do a focused cancer family history. I think that once you're in the high-risk category, people typically start discussing, "Should you be doing germline testing?" I think when there's a family history combined with being high-risk, it's really something more to make sure that conversation is had then. Not that it's emergent, of course, it's just to start that conversation. Yes, their family history of breast, prostate, pancreas, colon, et cetera, but that's part of their standard intake for us.

[Dr. Aditya Bagrodia]
I'm curious just logistics-wise when I was at UT Southwestern, anybody with a family history of high-risk or intraductal, they went to go see cancer genetics. On a move to San Diego, mostly due to practice patterns, availability of clinical geneticists, we were actually starting to order the germline testing. It's nice because we've had a couple of trials for say high-risk patients that have BRCA mutation that can get neoadjuvant PARP inhibitor. What do you all do? Is it you that's ordering germline testing, or making the referrals, or typically the urologist one step ahead? How does that work at your institution?

[Dr. Daniel Spratt]
It's different here. I've been at UH Seidman at Case for about two years. I think that a lot of us end up sending off through one of the industry tests rather than an in-house assay. Most of the time, probably the most common is I tell patients just to go to color.com. Not that I'm endorsing them, but one of these tests, because it just goes straight to the patient's house, they pay $250, or whatever the going rate is for it. A lot of patients seem to prefer that because it's like they get the results to them. It's not ordered through the hospital where they get a blood draw on things, but that's how most of it-- I think probably many of us ordered a different assay. We're working on a more standardized, you could call it, germline risk, or these high-risk clinics to standardize it. We've got a couple of different that, I would say are the most common people are ordering.

[Dr. Aditya Bagrodia]
I like that. I don't have any vested interest in ordering vitae because we have a workflow. We also have this study called THE PROMISE study, which is cool. The patient gets a pamphlet, they create their own portal, they get sent out a saliva swab and their own results and they can figure out who to share it with. I like getting away for some of that paternalistic, your physician has to be the quarterback for everything.

Listen to the Full Podcast

Radiotherapy for High Risk Prostate Cancer with Dr. Daniel Spratt on the BackTable Urology Podcast)
Ep 113 Radiotherapy for High Risk Prostate Cancer with Dr. Daniel Spratt
00:00 / 01:04

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Standardized Diagnostics in High-Risk Prostate Cancer

Following a comprehensive patient workup, the diagnostic journey for high-risk prostate cancer patients advances to tests and imaging procedures. Initial steps typically involve a prostate biopsy and MRI, often conducted prior to the patient's consultation with an oncology team. While these actions provide crucial insights, the diagnostic process proceeds with ordering a Prostate-Specific Membrane Antigen Positron Emission Tomography (PSMA PET) scan. Utilizing a radiotracer, the PSMA PET scan detects areas exhibiting heightened tracer uptake, indicating potential prostate cancer cell presence.


The PSMA PET scan is the gold standard for assessing metastasis, while the MRI predominantly aids in cancer staging. While both PSMA PET and MRI scans provide invaluable patient information, a pervasive challenge in healthcare is achieving consistency in interpreting these tests. Hence, it becomes imperative for physicians interpreting these tests to adhere to standardized reporting systems such as the Prostate-Specific Membrane Antigen Reporting and Data System (PSMA-RADS) and the Magnetic Resonance Imaging Reporting and Data System (MRADS). Employing PSMA-RADS and MRADS ensures that interpretation of outcomes are consistent, reliable, and easily transferable between medical professionals and healthcare facilities.

[Dr. Aditya Bagrodia]
Fantastic. We've gotten a good intake on things newly diagnosed. Talk a little bit about the next-- you mentioned germline testing. What's your ideal panel of staging, imaging, mandatory or highly preferred, other tests as you're formulating a treatment opinion?

[Dr. Daniel Spratt]
Yes. Typically next stage, assuming they're diagnosed, but if they've already had their biopsy and things of that nature is MRI and often here, we'd already have that before the biopsy, but an MRI of the prostate and then probably the vast majority of our patients, we get PSMA PET-CT, don't really have a preference. There's now even more on the market, but if for whatever reason they can't or if they came from the outside with, if it's a CT and bone scan, we would still repeat. We'd get a PSMA at that point. We don't get conventional imaging after the PSMA PET scan if that's done. That's the starting point because if there's metastasis, some of the other tests, like if we're going to order any biomarker tests, I wouldn't order that if the cancers' already spread to lymph nodes or distant mets.

[Dr. Aditya Bagrodia]
Sure. That's my imaging-wise preferred option. The MRI covers local staging, pelvic lymph nodes, and the PSMA PET and then I half-jokingly say that tumor board is, what do I do with this nonspecific PSMA PET finding in a rib? Have you found that that caused a lot of consternation? Is this something that's coming up or have your radiologists and nuclear medicine team inserted some phraseology to help diffuse anxiety?

[Dr. Daniel Spratt]
Yes. I was real lucky I was out last year in Australia and they've been doing PSMA PETs for much longer than us and actually we just had Luis Emmett, who's one of the big nuke meds out there who's led a lot of the studies with the groups. She just gave a didactic lecture to our team here, really calling out what she does and the importance, the various systems, there's PSMA-RADS, there's an MRADS or there's a variety of systems out there, but to really be very clear that these ribs are almost always-- if they don't have CT correlates and some other features, are false positives. They have actually great data where they leave these alone, where they actually have just done nothing and they show that patients after-- let's say they have a prostatectomy, PSA goes undetectable, so clearly these are not prostate cancer.
I think that's a big issue across the world actually but in the US when we got it up and running when I started here, there was these patients being called and you go from being a localized to a metastatic, and before you know it, someone's throwing them on ADT and abiraterone when it's really a run-of-the-mill intermediate-risk patient. We are trying to make a lot of progress and standardize things, but that was the intent of having her come out. I'd definitely recommend to anyone listening, it's worth inviting, even if you've got to pay her money to not over-call a lot of these soft calls.

[Dr. Aditya Bagrodia]
Yes, I definitely appreciate that. I literally have an unfavorable intermediate-risk prostate cancer that I'm seeing this morning. He's scheduled for our multidisciplinary clinic and he had a PSMA PET, SUVs a 2.4 in the third and fifth rib, they're nothing and he is freaking out, understandably. He is a professor here. Ideally PSMA PET, MRI pelvis, are you getting other testing? Say there is something suspicious, maybe going back to the chest on a PSMA PET, MRI chest, bone scan, is there any role for next testing and do you have a preferred one, Dan?

[Dr. Daniel Spratt]
I think it depends location and depends what's seen on the CT component of the PSMA. If you see something like, let's just take your example in a rib SUV two and a half, which is like nothing and if on the CT there's no sclerosis, there's literally nothing there, that's probably going to be a false positive. If there's maybe something but the resolution of the CT component, we often would get maybe either a more diagnostic CT. If it's a soft tissue area or if it's the spine, sometimes we'd be getting an MRI to follow up. I think some of these systems for PSMA PET, it's like we've incorporated PI-RADS, is I think these systems really should be quantified, obviously have your nuke med docs lead this effort, but pick something because that's the pretest probability, and if it's low, you probably want something else to confirm it. If it's high, you're good to go.

[Dr. Aditya Bagrodia]
Yes, it makes sense and I'm sure that on multiple levels this is going to be an evolution on how we synthesize that into our decision-making. Fantastic.

Radiation Therapy in High-Risk Prostate Cancer: When to Target the Lymph Nodes

Metastasis is a possible complication when dealing with prostate cancer and explains the much-needed attention to the lymph nodes surrounding the prostate and the seminal vesicles. When treating high-risk prostate cancer patients with radiation, it is also common practice to provide full-dose radiation to the seminal vesicles due to the elevated risk of cancer recurrence in this area post-treatment. However, the decision to irradiate nearby lymph nodes is not automatic and is typically reserved for instances of cancer recurrence. This cautious approach is influenced by considerations of the patient's quality of life.


Yet, if prostate cancer has advanced, extending beyond the prostate capsule or infiltrating the lymphatic system, radiation to these lymph nodes becomes warranted. Especially in cases classified as high-grade T3B disease, those with significantly elevated PSA levels, or if nodal involvement is detected, lymph node treatment is advised. Nonetheless, given the limited data supporting its efficacy, lymph node irradiation may not be pursued for cases with a Gleason PSA of 8 or 9.

[Dr. Aditya Bagrodia]
Lymph nodes, are you routinely rating them along with the prostate and the SVs or SVs, is that also part of your field?

[Dr. Daniel Spratt]
I always radiate full dose to the SVs. Especially in this PSMA PET era, the amount of isolated SV recurrences is just through the roof, but I actually typically do not radiate lymph nodes. I think that similar to the surgical trial data, and I know it's controversial of the benefit or lack of extended node dissection, it may be diagnostic, not therapeutic. We're not diagnostic by treating them. We're not gaining information. Again, if there's a recurrence in that node, you can give a nodal field later. I tend to, in most things, lead towards the side of quality of life. If it's T3B disease high grade or really high PSA or especially if it's node-positive, I definitely treat the lymph nodes, but run-of-the-mill Gleason PSA of 8 or 9, I wouldn't treat the nodes and just tell them that we really don't have fantastic data. We have one trial that's 250 patients that there's a benefit and multiple negative trials.

Podcast Contributors

Dr. Daniel Spratt discusses Radiotherapy for High Risk Prostate Cancer on the BackTable 113 Podcast

Dr. Daniel Spratt

Dr. Daniel Spratt is the chair of radiation oncology at University Hospitals (UH) Cleveland Medical Center Seidman Cancer Center and a professor with Case Western Reserve University in Cleveland, Ohio.

Dr. Aditya Bagrodia discusses Radiotherapy for High Risk Prostate Cancer on the BackTable 113 Podcast

Dr. Aditya Bagrodia

Dr. Aditya Bagrodia is an associate professor of urology and genitourinary oncology team leader at UC San Diego Health in California and adjunct professor of urology at UT Southwestern.

Cite This Podcast

BackTable, LLC (Producer). (2023, August 23). Ep. 113 – Radiotherapy for High Risk Prostate Cancer [Audio podcast]. Retrieved from https://www.backtable.com

Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.

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