Duration of testosterone suppression and the risk of death from prostate cancer in men treated with radiation and 6 months of hormone therapy
Bibliographic record
Abstract
We would like to thank Dr. D'Amico and his coauthors for elucidating a link between duration of androgen suppression after hormone therapy and risk of death from prostate cancer.1 Although all men in their study received 6 months of hormone therapy, a prolonged physiological effect from hormone therapy predicted improved prostate-cancer–specific survival. This is analogous to data from literature on breast cancer and hormone therapy. Tamoxifen is metabolized to endoxifen, which may be tamoxifen's most active metabolite, on the basis of individual cytochrome activity. In women who are prescribed equal doses of tamoxifen, individual rates of metabolism to endoxifen are predictive of relapse risk.2 In both of these studies, clinical outcome depended on individual exposure to the intended “agent” (estrogen blockade or testosterone blockade) rather than on the dose and duration of the prescription. The phenomenon of prolonged androgen suppression after cessation of hormone therapy in a cohort of patients from our institution was previously reported in Cancer.3 In that study, we demonstrated that factors associated with prolonged androgen suppression included advanced age, low baseline testosterone, and use of 3-month luteinizing-hormone–releasing hormone agonists (LHRH-a), compared to 1-month LHRH-a. In response to the current article by D'Amico et al, we analyzed outcomes—disease-specific survival and overall survival—for the same cohort that we have described previously.3 Prognostic factors including age, prostate-specific antigen (PSA), stage, Gleason score, radiotherapy dose, treatment year, hormone therapy duration, and androgen suppression duration (with recovery defined as 5 nmol/L testosterone) were examined by using Cox univariate and multivariate analyses. In the cohort as a whole, androgen-suppression duration after the end of hormone therapy was not predictive of outcomes. However, in men with Gleason scores of 8–10, androgen-suppression duration was the only predictor of disease-specific survival (hazard ratio [HR], 0.89 per month of androgen suppression; P = .035), and androgen-suppression duration showed a trend toward prediction of overall survival (HR, 0.93 per month of androgen suppression; P = .06). In contrast, hormone therapy duration did not predict either outcome. These results support findings by D'Amico and colleagues. D'Amico et al's article has drawn attention to the fact that as oncologists, we should endeavor to go beyond universally prescribed doses of hormonal agents. Further research should attempt to titrate these drugs to achieve the necessary effect in our patients, to maximize benefit, and to simultaneously minimize exposure to adverse effects. David Palma MD*, Tom Pickles MD*, * Radiation Oncology Program, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".