{"entity":{"id":"paper-hussain-swog-9346-intermittent-androgen-deprivation-nejm-2013","kind":"paper","name":"SWOG 9346: intermittent versus continuous androgen deprivation in metastatic prostate cancer","aka":["SWOG 9346","S9346","Hussain 2013 intermittent androgen deprivation"],"tldr":"Hormone therapy causes hot flushes, loss of libido, loss of muscle and bone, and low mood. This trial asked whether men could take breaks from it. After ten years the answer was uncomfortable: the breaks felt better for three months, and the trial could not rule out a worse chance of survival.","summary":"Maha Hussain and the Southwest Oncology Group enrolled 3,040 men with newly diagnosed metastatic hormone-sensitive prostate cancer, gave them seven months of androgen deprivation, and randomised the 1,535 whose prostate-specific antigen fell to 4 ng per millilitre or lower to continuous or intermittent therapy. The co-primary objectives were non-inferiority of survival, with an upper boundary on the hazard ratio of 1.20, and quality of life at three months.\n\nThe result is one of the most honestly reported inconclusive trials in oncology. Median survival was 5.8 years on continuous therapy and 5.1 years on intermittent, with a hazard ratio of 1.10 and a 90 percent confidence interval running to 1.23, which crosses the non-inferiority boundary without demonstrating inferiority either. Erectile function and mental health were better on intermittent therapy at month 3 and not afterwards.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2013","url":"https://doi.org/10.1056/nejmoa1212299"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23550669/"},{"label":"ClinicalTrials.gov NCT00002651","url":"https://clinicaltrials.gov/study/NCT00002651"}],"tags":["prostate-evidence"],"related":["paper-langley-lancet","paper-denmeade-transformer-bipolar-androgen-therapy-jco-2021","prostate-roadmap"],"cancers":["prostate","prostate-mhspc"],"sections":["hormonal","supportive-care"],"technologies":[],"targets":[],"drugs":["leuprolide","bicalutamide"],"companies":[],"institutions":[],"pathways":[],"terms":["adt","psa","quality-of-life","hazard-ratio","intermittent-androgen-deprivation","other-cause-mortality"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-trial-design","b-survivorship"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2013,"doi":"10.1056/nejmoa1212299","pmid":"23550669","authors":"Hussain M, Tangen CM, Berry DL, et al.","paperType":"rct","findings":["Median survival 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group; hazard ratio for death with intermittent therapy 1.10 (90 percent confidence interval 0.99 to 1.23).","The confidence interval exceeded the pre-specified upper non-inferiority boundary of 1.20, so a 20 percent greater risk of death with intermittent therapy could not be ruled out, and too few events occurred to demonstrate inferiority.","Median follow-up 9.8 years; 3,040 men enrolled and 1,535 randomised after the seven-month induction (765 continuous, 770 intermittent).","Intermittent therapy was associated with better erectile function (P less than 0.001) and mental health (P equals 0.003) at month 3 but not thereafter.","No significant differences between the groups in the number of treatment-related high-grade adverse events."],"whatItMeans":"The reason intermittent androgen deprivation is offered as a choice in metastatic disease rather than recommended, and a case study in what an inconclusive non-inferiority trial should say. For a man weighing the side effects, the honest statement is that the quality-of-life gain is real but brief and the survival question is open.","caveats":["Statistically inconclusive by the authors' own statement: neither non-inferiority nor inferiority was established.","Only men whose prostate-specific antigen fell below 4 ng per millilitre after seven months were randomised, so the result does not apply to men who do not achieve that response.","Standard of care has changed completely since enrolment: androgen deprivation alone is no longer first-line treatment for metastatic disease, so the question would have to be re-asked on top of a modern backbone."],"changedPractice":true,"participants":1535},"route":"/key-papers/paper-hussain-swog-9346-intermittent-androgen-deprivation-nejm-2013/","neighbours":{"paper":[{"id":"paper-langley-lancet","kind":"paper","name":"Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme","route":"/key-papers/paper-langley-lancet/"},{"id":"paper-denmeade-transformer-bipolar-androgen-therapy-jco-2021","kind":"paper","name":"TRANSFORMER: bipolar androgen therapy versus enzalutamide in asymptomatic metastatic castration-resistant prostate cancer","route":"/key-papers/paper-denmeade-transformer-bipolar-androgen-therapy-jco-2021/"}],"roadmap":[{"id":"prostate-roadmap","kind":"roadmap","name":"Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch","route":"/roadmaps/prostate-roadmap/"}],"cancer":[{"id":"prostate-mhspc","kind":"cancer","name":"Metastatic hormone-sensitive prostate cancer","route":"/cancers/prostate-mhspc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"section":[{"id":"hormonal","kind":"section","name":"Hormonal Therapy","route":"/fronts/hormonal/"},{"id":"supportive-care","kind":"section","name":"Supportive Care & Survivorship","route":"/fronts/supportive-care/"}],"drug":[{"id":"bicalutamide","kind":"drug","name":"Bicalutamide","route":"/drugs/bicalutamide/"},{"id":"leuprolide","kind":"drug","name":"Leuprolide (leuprorelin) and GnRH agonists","route":"/drugs/leuprolide/"}],"term":[{"id":"adt","kind":"term","name":"Androgen deprivation therapy (ADT)","route":"/terms/adt/"},{"id":"hazard-ratio","kind":"term","name":"Hazard ratio (HR)","route":"/terms/hazard-ratio/"},{"id":"intermittent-androgen-deprivation","kind":"term","name":"Intermittent androgen deprivation (IAD)","route":"/terms/intermittent-androgen-deprivation/"},{"id":"other-cause-mortality","kind":"term","name":"Other-cause mortality","route":"/terms/other-cause-mortality/"},{"id":"psa","kind":"term","name":"PSA (prostate-specific antigen)","route":"/terms/psa/"},{"id":"quality-of-life","kind":"term","name":"Quality of life","route":"/terms/quality-of-life/"}],"bottleneck":[{"id":"b-survivorship","kind":"bottleneck","name":"Survivorship and late effects are neglected","route":"/bottlenecks/b-survivorship/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"idea":[{"id":"idea-prostate-other-cause-mortality-as-a-reported-service-outcome","kind":"idea","name":"Report death from other causes as an outcome of the prostate cancer service, split by deprivation and ethnicity","route":"/ideas/idea-prostate-other-cause-mortality-as-a-reported-service-outcome/"}]}}