Ivan Kairatov has spent years at the crossroads of oncology and drug development, translating trial signals into day-to-day decisions for patients with localized prostate cancer. In this conversation, he unpacks new evidence showing that most of the value from androgen deprivation therapy (ADT) arrives early—within 9 to 12 months—then plateaus, while toxicity keeps climbing. He explains how a large meta-analysis reframes duration by risk group, how he personalizes plans alongside radiation, and why thoughtful cardiometabolic stewardship, bone health, and shared decision-making are as essential as any drug choice. You’ll hear practical clinic pathways, real patient vignettes, and a blueprint for the next generation of trials designed to right-size therapy without sacrificing cancer control.
Your study shows the steepest ADT gains occur by 9–12 months. Which outcomes improved most in that window, what benefits tapered after that, and can you share a patient story that makes the time curve feel real?
The clearest early wins were in cancer control outcomes—overall survival and cancer-specific survival improved most within the first 9 to 12 months. By the time patients reached that mark, the incremental protection from extending ADT further was modest, while non-cancer risks began to loom larger. In other words, the slope of benefit flattens after 12 months, but the slope of side effects keeps climbing. One patient I recall had intermediate-risk disease; his PSA became undetectable on radiation plus ADT by month 6 and stayed suppressed through month 12. We discussed going longer, but given the data that most benefit concentrates in those first 9–12 months, he stopped at a year. He later told me that by choosing that duration he felt we had “caught the wave” of benefit without riding it into rougher waters of metabolic and cardiovascular side effects.
Pooled across 10,266 men from 13 trials, what study features drove the signal, how did you align endpoints, and which checks convinced you the result was sturdy?
The signal was most apparent when trials included the full risk spectrum—low, intermediate, and high—because it let us see where duration matters and where it doesn’t. Radiation was consistently part of the backbone, with ADT as the intensification variable, which mirrors everyday practice. We harmonized endpoints around overall survival, cancer-specific survival, and non-cancer deaths so that cross-trial comparisons were apples to apples. Sensitivity analyses that sliced by risk category and ADT duration bands preserved the same core message: the majority of benefit accrues by 9–12 months. Subgroup cuts and leave-one-trial-out checks produced stable trends, giving us confidence this wasn’t a single-study artifact.
Guidelines have recommended 4–6 months for intermediate risk and 18–36 months for high risk. How do your findings recalibrate those ranges, and what decision pathway are you actually using in clinic today?
We recalibrate by pulling the median duration downward for many men. For intermediate-risk disease, we aim for 6 to 12 months; for high risk, up to 12 months often suffices; and for very high risk, we still consider going longer. In clinic, my decision path starts with risk group, then layers in age, comorbidities, and patient preference. If intermediate risk with favorable features, I counsel 6 months; if adverse features are present, I target 9 to 12 months. For high risk without ominous features, 12 months is my default; if very high risk, we discuss extending while acknowledging the rising cardiometabolic costs. Throughout, I emphasize that most of the value arrives by 9–12 months and personalize from there.
You highlight rising heart and metabolic risks with longer ADT. Which events concerned you most, and how do you screen, counsel, and co-manage to blunt that risk?
The big concerns are cardiovascular events and metabolic complications as duration stretches: heart issues, stroke risk surrogates, and new or worsened diabetes. While this analysis wasn’t designed to put precise absolute percentages on each event, the directional signal is clear: longer exposure raises non-cancer risks. My pathway is stepwise—baseline cardiovascular and metabolic assessment, then early engagement with primary care or cardiology when risks are notable. We focus on blood pressure control, lipid management, glucose monitoring, weight, and activity—small, consistent changes that add up. Education is explicit: ADT is powerful but not benign, so we plan protection alongside it.
For low-risk patients who may not need ADT at all, what tips you away from hormones, and how do you explain that choice to someone anxious about “doing enough”?
For truly low-risk disease, the data support omitting ADT, especially when radiation is well planned. I’m tipped away from hormones when the tumor biology is indolent and imaging doesn’t suggest hidden high-risk features. I tell patients that hormone therapy is not seasoning you add to every dish—it’s a strong spice with a cost. Skipping it here avoids bone and muscle loss, sexual side effects, and metabolic hits without sacrificing control. I recall a patient who clung to the idea that “more is better.” We reviewed that low-risk men often derive minimal incremental benefit from ADT; he chose radiation alone and maintained excellent quality of life with durable control.
In intermediate-risk disease, what nudges you to 6 months versus 12, how do you monitor during therapy, and what would prompt an early stop?
I lean toward 6 months for favorable intermediate-risk features and toward 9–12 months when features are less favorable. Monitoring is steady: clinical assessments and labs at regular intervals, plus close attention to symptoms and functional status. If a patient develops worrisome cardiometabolic signals or cumulative toxicity that outstrips expected cancer benefit, I’ll consider stopping at the earlier end of the planned window. Because most of the benefit concentrates by 9–12 months, trimming duration in the face of toxicity usually doesn’t sacrifice outcomes.
For high and very high risk, when is 12 months enough, when do you go longer, and can you walk us through a representative case?
For high risk without extremely aggressive features, 12 months often captures the lion’s share of benefit, especially with modern radiation. Very high-risk disease is where I still contemplate longer courses. A representative case: a fit patient with high-risk features started radiation plus ADT; by month 9, he had strong biochemical response and tolerable side effects. We completed 12 months, citing the early-benefit curve, and avoided extending because his non-cancer risks would only rise. In contrast, for a patient with very high-risk biology, I discuss the rationale for going beyond 12 months, while being upfront about cardiometabolic trade-offs and instituting preventive measures early.
How do age, baseline comorbidities, and fitness guide duration, and can you share an example where tailoring prevented a complication?
Age and comorbidity tilt the balance because competing mortality matters. An older man with multiple risk factors gains less from pushing past a year than a younger, robust counterpart. Fitness can widen options—fitter patients tolerate therapy better, but even then, the marginal benefit beyond 12 months is small for many. I recall a patient with notable cardiovascular risk; we targeted 9 months, co-managed with cardiology, and emphasized lifestyle changes. He finished without a cardiac event and regained energy quickly—an example of avoiding potential harm by aligning duration with the risk curve.
Bone and muscle loss are real with ADT. What is your prevention sequence, what goals do you set, and how do you track recovery after therapy ends?
I start bone health early. The sequence is simple: baseline assessment, calcium and vitamin D optimization, weight-bearing and resistance exercise, and consideration of bone-directed therapies if risk is high. We aim to preserve bone and muscle as therapy proceeds, then reassess after ADT to gauge recovery. Goals are practical—maintain strength and prevent clinically meaningful bone loss—paired with periodic reevaluation. Many patients describe the first signs of recovery as a return of steady energy and stamina in daily tasks after therapy concludes.
Radiation is nearly always paired with ADT. How do dose, fields, and techniques like IMRT or SBRT interact with shorter ADT, and how do you plan a case from simulation to first follow-up?
Modern radiation complements shorter ADT courses by tightening control where the cancer lives. Techniques such as precise planning and delivery allow us to leverage the early systemic effect of ADT without depending on long durations. My planning cadence: simulation to define targets, careful contouring of the prostate and relevant regions, dose selection matched to risk, and a schedule that meshes with a 6–12 month hormonal window. First follow-up focuses on symptoms, early efficacy signals, and whether we’re on track to conclude ADT at the preplanned mark—often 9 to 12 months for the majority who need it.
What quality-of-life gains do people feel with shorter courses, which domains improve first, and what patient-reported insights have shaped your practice?
Patients often notice early improvements in energy and mental clarity as they approach the end of a shorter course, with libido and overall vitality following after therapy stops. Shortening duration compresses the time spent in the fog of hormonal suppression. Patient reports about returning to exercise routines, better sleep, and fewer mood swings have reinforced my push to capture the benefits by 9–12 months and then stop. When patients can see the finish line at a year or less, adherence improves and the psychological burden lightens.
Shared decision-making is critical. What phrases and visuals help you convey “most benefit by 9–12 months,” and can you share a sample conversation?
I often say, “ADT gives us most of its protection in the first year; after that, the gains are small while the side effects grow.” A simple line graph sketch helps—benefit rising steeply to 9–12 months, then flattening, while a toxicity curve creeps upward. A typical conversation: “Given your risk, we can aim for 9 to 12 months. That’s where studies show most of the benefit. Going longer adds little for cancer control but more for heart and metabolic issues. Let’s plan for 9 months, reassess how you feel and how your labs look, and decide together whether to go to 12.”
Did any subgroups behave differently—by PSA, high-grade disease, or imaging features—and how should clinicians translate that into daily choices?
The broad picture held across subgroups: earlier benefits dominate, with diminishing returns afterward. Higher-risk biology understandably nudges consideration of longer therapy, especially in very high-risk settings, but even there the early window remains pivotal. Because our pooled approach was designed around overall patterns rather than single-biomarker cutoffs, I translate it this way: match duration to risk tier first, then modulate within that range based on clinical nuance. That keeps decisions grounded in the strongest signal we observed.
What studies or registries are still needed to fine-tune duration, which endpoints should matter most, and how would you design a pragmatic trial to guide 6 vs 9 vs 12 months?
We need trials that randomize modern radiation plus ADT at 6, 9, and 12 months with clear endpoints: overall survival, cancer-specific survival, non-cancer deaths, and quality of life. Competing mortality and metabolic events deserve equal billing because they’re not side notes—they’re central outcomes. A pragmatic design would embed in routine care, enroll across risk groups, and stratify by clinical features, with follow-up capturing both disease control and the lived experience. Add patient-reported outcomes and real-world adherence to ensure the results are immediately usable.
Implementation will decide how fast practice changes. What barriers do you see in clinics and with payers, what documentation helps, and how are you updating pathways and teams now?
Habits and historical guidelines are sticky, and some payers still expect longer durations for high-risk disease. The antidote is documentation: risk category, shared decision notes, and the evidence that most benefit accrues by 9–12 months. We’re updating pathways to reflect shorter, risk-tailored durations, training teams to counsel effectively, and aligning with primary care and cardiology for co-management. The goal is to make the right duration the easy default—clear orders, synchronized visit schedules, and education materials that show the benefit and toxicity curves at a glance.
Do you have any advice for our readers?
Anchor duration in risk, but let the person in front of you steer the fine-tuning. Aim to capture the early ADT dividend—usually by 9 to 12 months—and be intentional about stopping. Protect the heart, bones, and muscles as seriously as you treat the tumor. And bring patients into the math: when they see that the steep part of the benefit curve sits in the first year, they’re empowered to choose a plan that controls cancer and preserves life beyond it.
