IPCSG Newsletter 2026 April
ASK ME ANYTHING - YouTube
Advances in Prostate Cancer Diagnosis and Treatment: Insights from Dr. McCay's Annual Summit Presentation
Overview
This year's Informed Prostate Cancer Support Group annual summit featured an extended question-and-answer session with Dr. McCay, Medical Oncologist and Director of Clinical Studies Sciences at UC San Diego's Moores Cancer Center. Rather than a formal lecture, Dr. McCay opened the floor to our community, allowing participants to ask directly about their concerns—a format that proved invaluable for addressing the nuances of prostate cancer care. The following summary captures the key themes and emerging opportunities discussed, organized for patient accessibility.
PSMA PET Imaging: A Game-Changer in Detection and Staging
One of the most significant advances in prostate cancer management has been the FDA approval and clinical integration of PSMA-PET imaging. Unlike older imaging methods such as bone scans and CT scans, PSMA-PET is far more sensitive at detecting even small amounts of cancer spread. For men with biochemical recurrence (rising PSA after surgery or radiation), PSMA-PET has become the gold standard for determining whether cancer has metastasized.
Dr. McCay emphasized that PSMA-PET is especially valuable for men with high-risk disease or those showing signs of biochemical recurrence. The imaging relies on targeting a protein called prostate-specific membrane antigen, which cancer cells express in abundance. This approach has revolutionized how we identify metastatic disease at earlier, more treatable stages.
However, interpretation requires nuance. An isolated lesion detected on PSMA-PET—such as a small spot on a rib—does not automatically mean the cancer has spread systemically. False positives are common, and Dr. McCay cautioned against labeling someone with stage IV metastatic disease based on a single suspicious finding. Clinical context, PSA levels, and imaging patterns all matter when deciding next steps.
Clinical Pearl: PSMA-PET imaging can identify disease earlier, but isolated findings require careful interpretation. Work with your oncologist to integrate imaging results with your complete clinical picture—including your PSA trajectory, risk factors, and symptoms.
Biochemical Recurrence: Timing and Treatment Thresholds
Many participants asked about the "right time" to start treatment after surgery, when PSA begins to rise. Dr. McCay explained that the traditional threshold for biochemical recurrence has been a PSA of 0.2 ng/mL, but this number was defined decades ago before modern ultra-sensitive PSA testing existed. Today, a PSA below 0.1 typically warrants close monitoring but not immediate treatment.
For men in the 0.1–0.5 range, decisions depend on the rate of PSA rise (doubling time) and individual preferences. If PSA is stable or rising slowly, many physicians recommend watchful waiting combined with periodic PSMA-PET scans at a PSA above 0.5, when the likelihood of detecting metastases improves.
However, Dr. McCay stressed that waiting too long carries risk. Research, including the EMBARK trial, has shown that men with rapidly rising PSA (doubling time less than 12 months) and PSA greater than 1 benefit from starting hormone therapy early, even if PSMA-PET scans appear negative. Starting hormonal therapy at this threshold has delayed metastases and improved overall survival.
Hormone Therapy: Duration, Side Effects, and Newer Approaches
Androgen deprivation therapy (ADT) remains a cornerstone of prostate cancer treatment, particularly for intermediate- and high-risk disease. Dr. McCay reviewed the evidence for treatment duration, noting that the benefit from ADT is not linear over time. Most benefit accrues in the first three months; additional months provide diminishing returns. Recent meta-analyses suggest that if a patient cannot tolerate a prescribed course, stopping at 18 months rather than the planned 24 months likely sacrifices only single-digit percentage improvements in outcomes.
Dr. McCay also discussed important distinctions between different hormone therapies:
- Anti-androgens alone (enzalutamide, darolutamide, apalutamide) block testosterone from binding to cancer cells but do not lower testosterone levels; in fact, testosterone rises with these drugs. These approaches are non-castrating and carry less bone and muscle loss compared to drugs that completely suppress testosterone.
- GnRH agonists (Lupron, Trelstar) initially stimulate, then suppress, testosterone production in the testicles.
- Estrogen therapy via patch (not pills or gels) is castrating—it suppresses testosterone by negative feedback to the brain—and is experiencing a resurgence of interest for select patients.
For men concerned about side effects like neuropathy, Dr. McCay affirmed that dose adjustments or switching to alternative anti-androgens can be effective and should be discussed with your oncologist.
Managing Metabolic Syndrome and Cardiovascular Risk During ADT
One of the most important but under-recognized complications of long-term ADT is metabolic syndrome—a cluster of cardiovascular risk factors including insulin resistance, high blood sugar, elevated cholesterol, central obesity, and hypertension. More than 50% of men on long-term ADT develop metabolic syndrome, which significantly increases the risk of heart attack and stroke.
Dr. McCay stressed that prevention is far easier than treatment. She emphasized the importance of baseline screening and regular monitoring (at least annually) of lipid panels and hemoglobin A1C while on hormone therapy. Beyond lab work, she highlighted that robust exercise—particularly resistance training combined with functional fitness activities—is essential. Examples include exercises that maintain strength for daily activities: rising from a low couch, climbing stairs, carrying groceries, and hanging from a pull-up bar.
Regarding nutrition, Dr. McCay countered the notion that supplements are necessary. She pointed to the world's "blue zones"—regions where people live to 90 or 100 years old—and noted that longevity is not achieved through heavy supplementation but through plant-forward diets rich in whole foods, adequate protein (which need not come from animal sources), good sleep, stress management, and regular physical activity. Adequate protein intake is critical for maintaining muscle during ADT, but the best source is food, not pills.
Action Item for ADT Patients: Ask your oncology team to check your lipid panel and hemoglobin A1C annually. Partner with a nutritionist to calculate your protein needs (typically higher during ADT and exercise). Focus on functional fitness—movements that support daily life—rather than aesthetics alone.
Emerging Immunotherapies: T-Cell Engagers and Beyond
Traditional immunotherapies like checkpoint inhibitors (nivolumab, pembrolizumab) have largely failed in prostate cancer because the tumor microenvironment is "immunologically cold"—it suppresses immune infiltration. However, a new class of drugs called T-cell engagers (TCEs) is showing remarkable promise.
T-cell engagers are bispecific antibodies that act as a bridge: one end binds to a protein on cancer cells (such as PSMA or STEAP1), while the other end binds to immune T-cells. This brings the immune cell into direct contact with the cancer cell, allowing the immune system to attack without relying on traditional immune recognition mechanisms. Early-generation TCEs targeting PSMA showed proof of concept but had toxicity issues; newer agents, particularly STEAP1-targeted TCEs, are demonstrating improved efficacy with more manageable side effects.
Dr. McCay expressed excitement about TCEs, noting they are currently in phase 3 testing and may eventually move into earlier disease settings. She cautioned, however, that newer does not automatically mean better for every patient, and large clinical trials are needed to establish their role in treatment sequencing.
Salvage Radiation Therapy: Clearing Misconceptions
A common concern among men with biochemical recurrence after prostatectomy is the idea that salvage radiation therapy is "hitting a small nail with a large sledgehammer." Dr. McCay clarified that this framing misunderstands the biology. After surgery, even if no cancer is visible on imaging, microscopic disease is likely present in the pelvis. Salvage radiation, delivered to the prostate bed and pelvic lymph nodes, is curative for many men and should not be delayed simply because imaging appears negative.
She also addressed the proton versus photon debate. While protons theoretically have a slight advantage (no exit dose), the practical differences are minimal when photon therapy is optimally planned. If proton therapy is available without significant burden, it is reasonable to choose it; if not, modern photon therapy achieves excellent outcomes.
Finally, she discussed emerging hypofractionated approaches (SBRT—stereotactic body radiation therapy), which condense treatment into 5–10 days rather than 8–9 weeks. While promising, the long-term outcomes are still being evaluated, and SBRT is best suited for confined, early-stage disease, not advanced cases.
Biopsies and Risk Stratification: A Comprehensive Approach
Dr. McCay addressed the common question of whether MRI-guided targeted biopsies are sufficient or whether random biopsies are still needed. She noted that targeted biopsies alone can miss diffuse cancer. Prostate cancer often arises on the gland's periphery and can be widespread without forming a focal mass visible on MRI. The best diagnostic strategy combines both: MRI to identify visible lesions (and guide targeted sampling) plus systematic random sampling to detect microscopic disease elsewhere in the gland.
She also discussed cribriform architecture—a pattern of cancer cells seen under the microscope that is associated with more aggressive disease. However, cribriform pattern alone does not change treatment decisions; it is the totality of findings—Gleason score, PSA, stage, and genomic features—that matter.
The Complexity of Precision Medicine
When asked about genetic and genomic profiling to guide personalized therapy, Dr. McCay acknowledged tremendous progress but also enumerated the real-world challenges. Tumors are incredibly heterogeneous: not every cancer cell carries the same mutations, and a tissue sample from the prostate may not reflect what is happening in metastatic disease. Additionally, knowing a mutation exists does not guarantee a drug is available to target it, that multiple targeted drugs can be safely combined, or that the detected mutation is truly driving cancer growth rather than being an incidental finding.
Precision medicine is advancing rapidly, but it remains more art than algorithm. Dr. McCay cautioned against simplistic online narratives that suggest all answers are available if only doctors would "figure it out." The complexity is real, and she emphasized the importance of partnership with an experienced oncology team.
Practical Wisdom from a Patient-Centered Oncologist
When asked about her approach to shared decision-making, Dr. McCay offered insights relevant to all patients: Your role is to be informed and engaged. Her job is to present options, explain risks and benefits, and make a recommendation—but the final decision rests with you. She will not prescribe something she believes is harmful, but she respects that patients have different values and life circumstances. The most important relationship in your cancer care is the therapeutic alliance with your oncologist—a relationship built on mutual respect and honest communication.
Key Takeaways
- PSMA-PET imaging has revolutionized detection of metastatic disease but requires careful interpretation in partnership with your clinical team.
- Biochemical recurrence requires individualized decision-making; PSA thresholds and velocity matter, as does your overall risk profile.
- Hormone therapy remains highly effective but carries metabolic and cardiovascular risks that demand proactive monitoring and aggressive lifestyle intervention.
- Emerging T-cell engager therapies show exceptional promise and may reshape treatment sequencing in the coming years.
- Salvage radiation after biochemical recurrence is curative for many and should not be postponed while waiting for visible metastases.
- You are your own best advocate: ask questions, seek a second opinion if needed, and maintain a collaborative relationship with your care team.
Moving Forward: The landscape of prostate cancer care is evolving rapidly. Dr. McCay's emphasis on personalized, evidence-informed decision-making applies to every man in this community. Whether you are newly diagnosed, in active surveillance, navigating recurrence, or managing advanced disease, the principles of informed participation and therapeutic partnership remain constant. Your IPCSG community and resources, including our YouTube channel and hotline, are here to support you through every phase of your journey.
IPCSG Member Questions & Answers
Annual Summit with Dr. McCay, Medical Oncologist
UC San Diego Moores Cancer Center
Contents
Diagnostic Tools & Biopsies
Members asked about alternatives to needle biopsies, the role of MRI-guided sampling, and how imaging affects diagnostic strategy. Dr. McCay discussed risk assessment tools and the complementary use of different biopsy approaches.
A: Dr. McCay: Yes, there are tools to assess your risk of having clinically significant cancer before biopsy. These include urine-based tests that look at molecular signatures to estimate the likelihood of finding high-risk disease. MRI imaging also helps. However, the diagnosis of any malignancy (except hepatocellular carcinoma) is made histologically—by looking at tissue under the microscope. So while these prediction tests can reduce your need for biopsy, they're never 100% accurate.
A: Dr. McCay: Studies done at the NIH comparing targeted-only, random-only, and both approaches showed that the greatest detection rate was in patients who had both. MRI is good, but it's not microscopic-level imaging. Prostate cancer can be diffuse throughout the gland, and you can miss widespread disease if you only sample visibly suspicious areas. Prostate cancer often hides in regions where there's no focal lesion on imaging.
At UCSD, we do both: MRI-guided imaging followed by standard core biopsy with targeted areas. Some practices only do MRI after a cancer diagnosis is confirmed, which we think is backwards. We want the MRI to guide the biopsy, not the other way around.
A: Dr. McCay: Cribriform describes the way cancer cells look under the microscope—the pattern in which they're arranged in the tumor. It's been associated with somewhat more aggressive disease. Some studies show it's significant; others show it's not a clear independent factor. It often clusters with Gleason pattern 4, which is already known to be more aggressive.
At present, cribriform pattern by itself does not change treatment decisions. What matters is the total picture: Gleason score, PSA level, cancer stage, and molecular features. Yes, we assess cribriform, but the presence of cribriform alone is not the sole determinant of what we recommend.
Biochemical Recurrence & Monitoring
Many members had concerns about rising PSA after surgery or radiation, when to start treatment, and how PSMA-PET imaging helps guide decisions. Dr. McCay clarified thresholds, timing, and the importance of PSA doubling time.
A: Dr. McCay: The traditional threshold for biochemical recurrence is PSA 0.2 or higher, but that was defined in the pre-modern PSA testing era. With today's ultra-sensitive testing, we need to rethink those cutoffs.
If your PSA is less than 0.1, I would do nothing and monitor. Between 0.1 and 0.2, some doctors wait; others consider intervention based on doubling time. But you need several PSA readings to calculate true doubling time—it's not one or two points on a curve. Many patients come in with a single jump and think they're doubling, but that's not enough data.
A: Dr. McCay: This is a nuanced decision, not black and white. The absolute PSA value matters, but so do these factors:
- The rate of PSA rise (doubling time)
- Your baseline risk factors (Gleason score, stage at diagnosis)
- PSMA-PET imaging results
- Your overall health and life expectancy
- Whether you're willing and able to undergo salvage radiation
It's never just one number. Some men with a PSA in single digits but very rapid doubling (less than 6 months) need treatment; others with a PSA of 2 but stable, slow doubling can wait longer. Work with your oncologist to understand your specific risk profile.
A: Dr. McCay: You've maintained a very long disease course, which speaks to your management. The challenge is that without today's tools—PSMA-PET imaging, modern hormone therapies, targeted immunotherapies—treatment decisions 30+ years ago were based on different information. The landmark EMBARK trial, done a decade ago, showed that men with biochemically recurrent disease (PSA rising after definitive therapy) with a doubling time under 12 months benefited from early hormone therapy. That evidence wasn't available when you made your earlier decisions.
What matters now is optimizing your current treatment. The longer you've managed this, the more you've adapted, and that speaks to your resilience.
A: Dr. McCay: Not necessarily. Isolated PSMA-PET findings in the ribs come up in our tumor board nearly every week. The likelihood of a false positive is very high. You cannot and should not label someone as stage IV metastatic disease based on a single lesion.
A: Dr. McCay: This touches on a real clinical dilemma. PSMA-PET is incredibly sensitive, but if you wait for visible metastases before treating, you may miss a window for earlier intervention with better outcomes. The EMBARK trial addressed this: men with PSA greater than 1 and doubling time less than 12 months benefited from starting hormonal therapy even with a negative PET scan.
The challenge is knowing when to pull the trigger without overtreating. Some men develop visible metastases quickly; others remain biochemically recurrent for years. You don't want to start hormone therapy unnecessarily, but you also don't want to wait so long that disease becomes widely metastatic and harder to treat. This is where working with an experienced oncology team and understanding your own PSA kinetics becomes essential.
Hormone Therapy Options & Strategies
Members asked about different anti-androgen drugs, when to use them, side effect comparisons, and how to manage tolerance issues. Dr. McCay explained the distinctions between castrating and non-castrating approaches.
A: Dr. McCay: There are three FDA-approved anti-androgens: enzalutamide (Xtandi), darolutamide (Nubeqa), and apalutamide (ARN-509). These are all androgen receptor antagonists—they block testosterone from binding to the androgen receptor. There are probably more similarities than differences among them, but each has a distinct drug-drug interaction profile and side effect profile.
Darolutamide is the newest. There's no difference in efficacy compared to enzalutamide, but some patients who don't tolerate enzalutamide do better on darolutamide. The reason: darolutamide does not cross the blood-brain barrier as much, so it causes less fatigue, fewer falls, and fewer cognitive issues compared to enzalutamide or apalutamide.
A: Dr. McCay: Yes, absolutely. Dose adjustments are reasonable and can be effective. If you're tolerating the lower dose with good PSA control, that's a valid approach. You don't always need to stick to the standard dose if a lower dose works for your situation.
A: Dr. McCay: Great question. Let me break this down:
Non-castrating strategies: Anti-androgens by themselves (enzalutamide, darolutamide, apalutamide) block testosterone from binding to the androgen receptor, but they don't lower testosterone levels. In fact, testosterone rises on these drugs. They're called non-castrating because your testosterone level stays higher.
Castrating strategies: These actually lower testosterone:
- GnRH agonists (Lupron, Trelstar): These continuously stimulate a receptor in the brain, which paradoxically shuts down testosterone production in the testicles. It's like keeping the accelerator pressed—eventually the system gets exhausted and stops.
- GnRH antagonists: These just turn the signal off immediately, without the initial stimulation.
- Estrogen (via patch): Estrogen therapy is castrating. It suppresses testosterone through negative feedback to the brain. There's been a recent resurgence of interest in estrogen, especially the transdermal patch (not pills or gels).
Non-castrating therapies tend to have less impact on bone density and muscle loss compared to fully castrating approaches. However, because testosterone rises with anti-androgens alone, you may have more hot flashes and breast tenderness.
The choice depends on your specific situation, risk factors, and tolerance.
A: Dr. McCay: Yes, you can build muscle on hormone therapy, but it's hard—much harder than without it. It requires dedication to resistance training, proper nutrition, and honest calculation of your macronutrient intake.
A: Dr. McCay: No. You need to calculate your macronutrient needs—all three macros: protein, carbohydrates, and fats. There's an actual formula for this, based on your goals and current body composition. Meeting with a nutritionist can help you determine how many total calories you need and how to split those calories across the three macros. It's not just about protein; it's a balanced equation.
If you're constantly hungry while trying to control weight gain on ADT, a nutritionist can help identify whether you're undereating calories overall, eating at the wrong times of day, or not hitting the right macro balance.
ADT Side Effects & Management
Members raised concerns about hot flashes, metabolic syndrome, muscle loss, cardiovascular risk, and what can be done to prevent or manage these complications during hormone therapy.
A: Dr. McCay: The problem isn't Lupron still being in your system. The drug itself is metabolized and gone (within a few months after your last injection). The issue is that the GnRH receptor in your brain has been shut down by the continuous stimulation from Lupron. Even after you stop the drug, the receptor hasn't woken back up yet. In some patients, it can take a very long time—even indefinitely—for the receptor to recover.
Hot flashes are notoriously difficult to treat. Beyond medication adjustments to your home (AC settings, lighter clothing, fans, cooling pads), there are pharmaceutical options: venlafaxine (an antidepressant), low-dose estrogen, oxybutynin, gabapentin—but none are magical cures. Each has its own side effects.
A: Dr. McCay: First, the protein you eat is NOT feeding your cancer cells. Dissociate those two ideas. Protein is essential for maintaining and building muscle, regardless of your testosterone status.
Second, while it's true that building muscle on low testosterone is harder, it's not impossible. The challenge is that most people think they're doing what they need to do—eating well, exercising—but they're not calculating precisely. If your goal is to build lean mass, you need resistance training, calculated protein intake, proper calorie balance, and consistency. Most people don't meet those standards. But it CAN be done.
More importantly, focus on functional fitness: the strength you need to get up from a low couch, climb stairs, carry groceries, hang from a pull-up bar. These are the movements that keep you independent as you age.
A: Dr. McCay: Metabolic syndrome is a cluster of conditions that often develop during ADT: insulin resistance leading to high blood sugar (the insulin isn't working properly), elevated cholesterol, weight gain (especially abdominal/visceral fat), and high blood pressure. Many people don't feel it—you may not notice when your blood sugar or blood pressure is elevated. But it significantly increases your risk of heart attack and stroke.
Reversing metabolic syndrome after it develops is harder than preventing it, so prevention is the priority.
A: Dr. McCay: My bias: get your nutrients from food, not pills. There's no substitute for whole food sources of protein—whether from animal or plant sources. When we look at the world's "blue zones" where people live to 90–100 years old, none of them rely on heavy supplementation. They eat from the earth, they have a plant-forward diet with some animal protein (often fish), and they're not loading up on supplements.
That said, if you have a specific deficiency or allergy that requires supplementation, absolutely do it. But for most people, the focus should be on adequate whole-food protein intake, not pill-based supplements.
A: Dr. McCay: It depends on your risk factors and which drugs you're taking. If you're on abiraterone (Zytiga), we need to monitor liver function and potassium regularly. For most men on standard ADT, I recommend at least annual checking of:
- Lipid panel (cholesterol, triglycerides)
- Hemoglobin A1C (blood sugar control)
- DEXA scan (bone density)
The problem I see in practice is that sometimes nobody is owning this—it's unclear whether your primary care doctor, your urologist, or your oncologist is supposed to do it. I try not to assume someone else is checking these things. In my practice, we monitor at least annually. In other settings, your PCP might do it. The key is making sure someone is actually doing it.
Radiation Therapy Strategies
Members had questions about salvage radiation after biochemical recurrence, proton versus photon therapy, SBRT (stereotactic body radiation), and hydrogel spacers. Dr. McCay addressed misconceptions and explained the evidence.
A: Dr. McCay: I understand the intuition, but here's the biology: after surgery, even if your PSMA-PET scan looks normal, there's likely microscopic disease present in the pelvis. We can't see it, but the high probability it's there is based on your PSA doubling time, Gleason score, and stage at diagnosis.
Salvage radiation therapy is designed to treat the prostate bed and the pelvic lymph nodes—the region most likely to harbor that microscopic disease. If we treat adequately, we can be curative. If we wait for visible metastases before treating, you've already missed the window for cure.
Salvage radiation IS a curative option for many men. It's not curative for everyone, but the alternative—waiting for PSMA-PET to show something—means you've likely progressed beyond salvageability.
A: Dr. McCay: Theoretically, protons have one advantage: there's no exit dose. With photons, radiation passes through the tumor and continues beyond it, potentially damaging tissue on the other side. Protons stop at a specific depth (the Bragg peak), so there's no exit dose.
However, when we look at actual clinical trial data comparing photons and protons side by side, the objective outcomes are essentially the same. Not "about the same"—actually the same. Proton therapy is more expensive and less accessible than photon therapy.
A: Dr. McCay: SBRT delivers highly focused radiation in just 5–10 days instead of 8–9 weeks. It's elegant—fewer treatments, same dose per day is higher, and it's convenient.
The challenge: long-term outcomes are still early. These studies were done recently, and we're looking at 5-, 10-, and 15-year survival data. We don't yet have decades of follow-up to confidently say SBRT is superior to conventional radiation from an oncologic standpoint.
SBRT works best for confined, early-stage disease. If there's evidence of extra-prostatic disease (cancer extending outside the gland), you can't use SBRT because you'd be missing microscopic disease in the surrounding pelvis.
A: Dr. McCay: There's been a lot of talk about hydrogel spacers or other spacers, but there's never been a formal randomized trial comparing patients who got spacers to those who didn't, looking at outcomes. Such a trial would be logistically challenging to conduct.
Theoretically, a spacer pushes the rectum away, reducing radiation dose to rectal tissue. But the concern is: what if you're also pushing tumor away? And the procedure itself—injecting a gel—isn't without risk or discomfort.
I don't think hydrogel spacers are a "must-do." They're a "can-do" in certain scenarios. The evidence just isn't strong enough to mandate them universally.
Emerging Therapies & Immunotherapy
Members asked about new immunotherapy approaches, T-cell engagers, alpha-emitting radiopharmaceuticals, and combination strategies. Dr. McCay discussed why prostate cancer has been resistant to traditional immunotherapy and how new approaches are changing that.
A: Dr. McCay: Traditional checkpoint inhibitors (like nivolumab or pembrolizumab) have largely failed in prostate cancer because the tumor microenvironment is "immune-cold"—there aren't many immune cells infiltrating the tumor to begin with.
T-cell engagers are bispecific antibodies—they have two binding sites. One binds to a protein on the cancer cell surface (like PSMA or STEAP1), and the other binds to a T-cell. This bridges the cancer cell and the immune cell, bringing them into direct contact. The T-cell can then do what it's supposed to do: kill the cancer cell. This bypasses the need for traditional immune recognition mechanisms.
Early T-cell engagers targeting PSMA showed proof of concept but had toxicity issues because they overactivated the immune system and caused a cytokine storm. Newer agents, particularly STEAP1-targeted T-cell engagers, are showing more promise with better toxicity profiles.
A: Dr. McCay: I need to be direct: there's an entire unregulated industry that preys on cancer patients. I see it every day in my clinic. Patients have put their homes on the line for unproven intravenous stem cell therapies that claim to cure cancer. It's heartbreaking.
The neutraceutical industry is largely unregulated. I can make a B12 supplement in my garage, put it in a bottle, and sell it legally. Be very careful. Apply the same level of scientific rigor to supplements as you would to a medication I prescribe.
Regarding NK cell therapies: yes, they do have potential. CAR-NK cell therapies are being developed, similar to CAR-T cell therapies. But they're still in very early infancy—we don't yet have an effective, safe way to enhance and administer NK cells. This is a future direction, not a current standard of care.
A: Dr. McCay: There are no current studies where patients receive lutetium and actinium concurrently (at the same time). There are studies where patients received one (like lutetium), and then later enrolled on a trial with the other (like actinium). Some trials allow prior lutetium; others don't.
I do think there's a place for both agents. The biggest concern with these radioarmaceuticals is downstream bone marrow toxicity—they're DNA-damaging agents, and long-term exposure carries risks of secondary malignancies and bone marrow damage.
To your broader question of why we can't use these drugs earlier in localized disease: the FDA considers them myelodamaging agents. If someone has a life expectancy of 10+ years after treatment, we have to worry about what happens down the road. We don't want to open a black box of late toxicities.
A: Dr. McCay: Yes, I love the PREDICT trial—it's what I call a "unicorn study." It matched patients' tumors to drug combinations based on molecular profiling and gave them FDA-approved drugs in novel combinations.
The trial demonstrated that matching patients' tumor profiles to drug therapies improved outcomes compared to standard of care—patients did better when they were matched. We kept disease at bay for many patients for extended periods beyond what standard therapy would have achieved.
Was it a cure-all? No. But it proved the principle that precision-matched therapy can work. The biggest challenge in running such a trial was logistical and financial: getting insurance approval for off-label drug uses, managing drug interactions, and dose-reducing when combining multiple drugs that had never been combined before.
Clinical Trials & Research
Members asked about the EMBARK trial, the I-PREDICT trial, family history and genetic testing, and how clinical trial design affects the availability of new therapies.
A: Dr. McCay: EMBARK studied men with biochemically recurrent prostate cancer (PSA rising after definitive therapy—surgery or radiation) where the cancer hadn't yet been detected on imaging. The trial showed that men with a PSA greater than 1 and a doubling time less than 12 months benefited from starting hormone therapy early, even without visible metastases.
The benefit was significant: delayed metastases and improved overall survival. This trial, published over a decade ago, changed our approach to biochemical recurrence. If your PSA is rising rapidly (doubling in under a year) and hits 1 or higher, we don't wait for imaging to show something—we start treating.
A: Dr. McCay: Yes. Strong family history is a risk factor. Current guidelines recommend germline genetic testing for men with unfavorable intermediate-risk, high-risk, or very high-risk prostate cancer. I personally believe every man with prostate cancer should get germline testing—the guidelines haven't caught up yet, but the evidence supports it.
If you have a family history like yours, you absolutely should be offered genetic testing. This information helps guide treatment decisions and screening for other family members.
A: Dr. McCay: This is a critical question that highlights the gap between what we hope works and what regulators require. For early-stage disease like biochemical recurrence, patients feel good, have no symptoms, and only show rising PSA. To study a therapy in that setting, regulators require proving the drug either delays metastases or improves overall survival—not just makes PSA go down.
With PSMA-PET imaging now available, you might think detecting metastases earlier would help, but the FDA's position is: if you detect a small spot on a rib, does that count as clinically significant disease? Does treating it change overall survival? We haven't proven that yet. So even PSMA-PET positivity doesn't automatically justify approving a drug for that indication.
Patient Care Philosophy & Shared Decision-Making
Members asked about Dr. McCay's approach to treatment decisions, how she balances patient input with medical recommendations, and how patients can be engaged partners in their care.
A: Dr. McCay: That's generally not my style—putting my foot down. I've got four kids and a husband; I get trampled in multiple directions constantly. But seriously, patient care is about serving the needs of our patients. Everybody comes to the table with different values and different needs.
My job is to make sure you're informed: aware of the risks and benefits of any choice. Whether you follow my recommendation or not is ultimately your choice. You're all grown men; it's your decision, not mine.
If I think something is going to be detrimental, I'll tell you. But I won't prescribe something I believe is harmful. That said, I won't necessarily preclude you from seeking another opinion from someone willing to prescribe it.
A: Dr. McCay: (In response, another patient in the room shared: "I had surgery from the same surgeon as you, then I became a patient of Dr. McCay's, and I saw much more cutting-edge ideas and diagnostics, plus better bedside manner. I highly recommend making a change.")
Dr. McCay: We're here to help any way we can. While long-standing relationships with a trusted provider are valuable, if you feel you're not getting access to the latest information or approaches, a second opinion is always reasonable. In oncology, being aware of emerging therapies and having access to clinical trials can make a real difference in outcomes.
A: Dr. McCay: "You've seen one prostate cancer, you've seen one prostate cancer." Every patient is different. The complexity of a complete medical case—your comorbidities, other medications, disease characteristics, genomics—is impossible for a lay person browsing the internet to fully understand.
People online sharing their experiences are sharing one piece of the pie. They don't know your full context, and you don't know theirs. What worked for one person may be exactly wrong for another.
A: Dr. McCay: You are your own case manager. The more you understand about prostate cancer and the better educated you are, the better CEO of your health you can be. That means asking informed questions, getting to know your disease characteristics, understanding your options, and maintaining an active dialogue with your care team.
You're not a medical professional, and we don't expect you to be. But informed participation—reading reputable sources, asking thoughtful questions, expressing your values and preferences—is essential. That information helps me tailor my recommendations to YOU, not to a generic patient.
Editor's Note: A participant summarized a key theme from the discussion: "There's a lot of treatment out there, and Dr. McCay is helping us navigate it. We're lucky to have access to cutting-edge thinking and care."
Sources and Citations
1. PSMA-PET Imaging Standards and Clinical Applications
Tsechelidis I, Vrachimis A. "PSMA PET in Imaging Prostate Cancer." Frontiers in Oncology, vol. 12, 2022, article 831429. DOI: 10.3389/fonc.2022.831429.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8832487/
2. PSMA-PET Imaging in the Modern Era
Ananthapadmanabhan A, et al. "PSMA-PET – Prostate Cancer Imaging in the Modern Era." Trends in Urology & Men's Health, Wiley Online Library, 2025. DOI: 10.1002/tre.70001.
https://onlinelibrary.wiley.com/doi/10.1002/tre.70001
3. PSMA-PET Imaging: Role in Staging and Biochemical Recurrence
Islam R, Desai S, Moran M, Golombos DM. "The Role of PSMA PET Imaging in Prostate Cancer: Current Applications and Future Directions." Current Urology Reports, vol. 26, 2025, article 1268-2. DOI: 10.1007/s11934-025-01268-2.
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4. FDA-Approved PSMA-PET Imaging Agents
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196200/
5. T-Cell Engagers: Emerging Immunotherapy Frontier
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6. BiTE Therapies in Solid Tumors and Prostate Cancer
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7. T-Cell Redirecting Therapies in Advanced Prostate Cancer
Boorjian SA, et al. "T-Cell Redirecting Bispecific Antibodies: A Review of a Novel Class of Immuno-Oncology for Advanced Prostate Cancer." Journal of Clinical Medicine, vol. 12, no. 10, 2023, article 3472. DOI: 10.3390/jcm12103472.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11135853/
8. T-Cell Engagers at ESMO 2024
Agarwal N (Presenter). "T Cell Engagers in Prostate Cancer." ESMO 2024 Conference, Barcelona, Spain, September 13–16, 2024. UroToday Conference Highlights.
https://www.urotoday.com/conference-highlights/esmo-2024/esmo-2024-prostate-cancer/154834-esmo-2024-t-cell-engagers-in-prostate-cancer.html
9. Metabolic Syndrome and ADT Complications
Keating NL, O'Malley AJ, Freedland SJ. "Metabolic Complications and Increased Cardiovascular Risks as a Result of Androgen Deprivation Therapy in Men with Prostate Cancer." Journal of Urology, vol. 176, no. 2, 2006, pp. 465–471. DOI: 10.1016/j.juro.2006.03.039.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3200266/
10. Exercise Interventions for Metabolic Syndrome in Prostate Cancer
Cormie P, Atkinson M, Bucci L, et al. "A Review of Clinical Effects Associated with Metabolic Syndrome and Exercise in Prostate Cancer Patients." Supportive Care in Cancer, vol. 22, no. 12, 2014, pp. 3169–3177. DOI: 10.1007/s00520-014-2330-2.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099103/
11. ADT and Cardiovascular Toxicity: Meta-Analysis
Zhong S, Jiang T, Zhang W, et al. "Cardiovascular Effects of Androgen Deprivation Therapy in Prostate Cancer: Contemporary Meta-Analyses." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 40, no. 5, 2020, pp. 1218–1227. DOI: 10.1161/ATVBAHA.119.313046.
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12. Metabolic Monitoring Guidelines for ADT Patients
Kulkarni GS, Finelli A, Hanna S, et al. "Metabolic, Cardiac, and Bone Health Testing in Patients with Prostate Cancer on Androgen-Deprivation Therapy: A Population-Based Assessment of Adherence to Therapeutic Monitoring Guidelines." Cancer, vol. 131, no. 1, 2025, pp. 80–92. DOI: 10.1002/cncr.35039.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11694232/
13. Stereotactic Body Radiotherapy for High-Risk Prostate Cancer
Correa RJM, Loblaw A. "Stereotactic Body Radiotherapy: Hitting Harder, Faster, and Smarter in High-Risk Prostate Cancer." Frontiers in Oncology, vol. 12, 2022, article 889132. DOI: 10.3389/fonc.2022.889132.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301671/
14. SBRT for Prostate Cancer: Clinical Applications and Outcomes
Mayo Clinic Staff. "SBRT for Prostate Cancer: How it Compares to Other Treatments." Mayo Clinic, December 2025. Evidence synthesis of recent trials including van As N, et al. "Radical Prostatectomy Versus Stereotactic Radiotherapy for Clinically Localised Prostate Cancer: Results of the PACE-A Randomised Trial." European Urology, vol. 86, no. 5, 2024, pp. 496–505.
https://www.mayoclinic.org/diseases-conditions/prostate-cancer/in-depth/sbrt-for-prostate-cancer/art-20592262
15. PSMA-PET and FDG-PET in Advanced Prostate Cancer
Clinical Trial: "Dual PSMA and FDG PET Imaging for Patients With Advanced Prostate Cancer." Principal Investigator: Ur Metser, MD. National Institutes of Health, ClinicalTrials.gov Identifier: NCT06335914. Study Start: April 3, 2025; Completion: March 4, 2029.
https://clinicaltrials.gov/study/NCT06335914
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