Biochemical Recurrence After Prostatectomy: When to Start ADT
A rising PSA with no detectable metastatic disease anywhere — the actual disagreement isn't about the biology, it's about whether starting hormone therapy now for a survival benefit measured in months is worth the years of hypogonadism it would buy an otherwise healthy 68-year-old.
H.P., a 68-year-old man, retired two years ago from three decades teaching high school chemistry, and has spent most of that time restoring his relationship with distance cycling, a hobby he set aside for most of his working life and has now taken up seriously again, riding forty or more miles most weekends with a club of other retirees. His radical prostatectomy for Gleason 7 disease was four years ago, with an undetectable PSA at his first postoperative check. It has since risen slowly across annual labs to 0.6ng/mL, with a calculated doubling time of roughly fourteen months — a biochemical recurrence, confirmed on repeat testing, with no detectable disease on conventional or PSMA PET imaging. He has no cardiovascular disease, no diabetes, and a bone density scan within the normal range, which matters directly to what starting ADT now would actually cost him.
The evidence for immediate versus deferred ADT in this exact situation is real but modest: TOAD (Duchesne et al.) randomized 293 men and found immediate initiation improved overall survival, its primary endpoint — 91.2% against 86.4% at five years — but the margin was narrow enough that the log-rank p sat at 0.047, and the benefit came bundled with the full metabolic and functional cost of sustained hypogonadism — reduced bone density, muscle mass loss, cardiovascular risk, and a direct hit to the endurance training he has only recently returned to. His fourteen-month doubling time sits on the slower end of the range associated with a longer interval before metastases typically appear, which is itself a reason some clinicians would delay ADT until doubling time shortens or metastatic disease actually shows up on imaging, rather than treat a PSA number alone as the trigger. His cycling club has been the other consideration he keeps returning to at each visit — several of the men he rides with are themselves cancer survivors who started hormone therapy years earlier, and he has watched their endurance decline in ways he associates directly with treatment rather than age alone, whether or not that association would hold up to a formal comparison.
An annual follow-up visit that became a real decision
I'd start ADT now. TOAD's primary endpoint was overall survival and it was met — 91.2% against 86.4% at five years, in men with PSA relapse and no detectable metastases. The margin is modest, but it's a survival margin, and starting now captures it at the point in his disease where the trial actually showed it.
His doubling time is fourteen months — on the slower end of the range associated with a long interval before metastases typically appear. And I'd look harder at who drove TOAD's result before applying it to him: a prespecified subgroup analysis found the survival benefit concentrated in men who had received ADT before trial entry. He hasn't. He had a prostatectomy and nothing since. The slice of that trial he actually resembles is the one where the effect largely wasn't there. Against that, the full cost of sustained hypogonadism: bone density loss, cardiovascular risk, and a real hit to the endurance training he's only recently gotten back to. I'd defer until his doubling time shortens or metastatic disease actually appears on imaging.
A modest average benefit in a trial population isn't the same as a modest benefit for a patient whose own kinetics put him toward the slower, lower-risk end of that population.
I don't think either of you is wrong on the evidence — this is genuinely close, and I'd frame it to him exactly that way rather than as a recommendation with a clear right answer. He's spent his retirement rebuilding his cycling. I'd lay out the modest survival data against the real years of functional cost, and let him decide which side of that tradeoff matters more to him, with both of you available to answer his specific questions rather than steering him toward either path.
Agreed: no medication started today. Repeat PSA and clinical reassessment in three months, with imaging repeated if doubling time shortens meaningfully or he develops any new symptoms.
Not agreed, and explicitly left as the patient's own decision rather than the team's:
Would recommend starting ADT at the next visit regardless of whether doubling time changes, given TOAD's demonstrated benefit.
Would continue deferring unless doubling time clearly shortens or imaging becomes positive, given his currently favorable kinetics.
Both physicians agreed the patient should hear the tradeoff stated plainly at his next visit — the modest survival data on one side, the real years of functional and metabolic cost on the other — and that his own answer, not either physician's default preference, should decide what happens next.