{"entity":{"id":"paper-vale-stopcap-docetaxel-bisphosphonates-lancet-oncol-2016","kind":"paper","name":"STOpCaP: docetaxel or bisphosphonates added to standard of care in hormone-sensitive prostate cancer, a systematic review and meta-analysis","aka":["STOpCaP","Vale 2016 docetaxel meta-analysis","adaptive meta-analysis prostate docetaxel"],"tldr":"Three trials of chemotherapy at the start of hormone therapy had reported, two positive and one negative. Pooling them showed the treatment does work in metastatic disease, improving four-year survival by about nine percent, and that zoledronic acid does not.","summary":"Claire Vale, Jayne Tierney and the STOpCaP steering group ran a framework for adaptive meta-analysis over every randomised trial of docetaxel or bisphosphonates added to standard care in high-risk localised or metastatic hormone-sensitive prostate cancer, taking hazard ratios from publications, presentations and directly from investigators.\n\nThis is the paper that settled the contradiction between GETUG-AFU 15, CHAARTED and STAMPEDE, and it is worth reading for its method as much as for its result: an adaptive meta-analysis is designed to be run while trials are still reporting, rather than years afterwards. It also did something rarer, which is to close a question in the negative: it found no evidence that zoledronic acid improves survival in either metastatic or non-metastatic disease.","asOf":"2026-09-25","links":[{"label":"Lancet Oncol 2016","url":"https://doi.org/10.1016/s1470-2045(15)00489-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26718929/"}],"tags":["prostate-evidence"],"related":["paper-gravis-getug-afu-15-docetaxel-lancet-oncol-2013","paper-chaarted-nejm-2015","paper-stampede-lancet-2016","prostate-roadmap"],"cancers":["prostate","prostate-mhspc"],"sections":["chemotherapy","hormonal"],"technologies":[],"targets":[],"drugs":["docetaxel","zoledronic-acid"],"companies":[],"institutions":[],"pathways":[],"terms":["adt","hazard-ratio","bone-metastases"],"trials":[],"people":["nicholas-james","karim-fizazi","christopher-sweeney"],"bottlenecks":["b-trial-design","b-negative-results","b-knowledge-diffusion"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2016,"doi":"10.1016/s1470-2045(15)00489-1","pmid":"26718929","authors":"Vale CL, Burdett S, Rydzewska LHM, et al.","paperType":"meta-analysis","findings":["In metastatic disease, docetaxel added to standard of care improved survival: hazard ratio 0.77 (95 percent confidence interval 0.68 to 0.87; p less than 0.0001), an absolute improvement in four-year survival of 9 percent (5 to 14), from three trials covering 2,992 of 3,206 randomised men.","Failure-free survival hazard ratio 0.64 (0.58 to 0.70; p less than 0.0001), a reduction in absolute four-year failure rates of 16 percent (12 to 19).","In locally advanced (M0) disease, no evidence of a survival benefit from docetaxel: hazard ratio 0.87 (0.69 to 1.09; p equals 0.218) from three trials covering 2,121 of 3,978 men, although failure-free survival improved (0.70, 0.61 to 0.81).","No evidence that zoledronic acid improves survival in metastatic disease (hazard ratio 0.94, 0.83 to 1.07; p equals 0.323) or in M0 disease (0.98, 0.82 to 1.16; p equals 0.782).","The bisphosphonate survival signal in metastatic disease (0.88, 0.79 to 0.98; p equals 0.025) was influenced by the positive result of one trial of sodium clodronate."],"whatItMeans":"The answer to a question three individual trials could not answer on their own, and the reason docetaxel with androgen deprivation became standard for metastatic hormone-sensitive disease. It also stopped a widely used bone drug being credited with a survival effect it does not have.","caveats":["An aggregate-data meta-analysis, not individual patient data, so subgroup effects such as disease volume cannot be examined directly.","The M0 result rests on fewer than two thirds of the randomised men, because survival data were not available from every trial.","Standard of care has since changed: the comparator arms received androgen deprivation alone, while today they would usually receive an androgen receptor pathway inhibitor as well."],"changedPractice":true},"route":"/key-papers/paper-vale-stopcap-docetaxel-bisphosphonates-lancet-oncol-2016/","neighbours":{"paper":[{"id":"paper-stampede-lancet-2016","kind":"paper","name":"Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial","route":"/key-papers/paper-stampede-lancet-2016/"},{"id":"paper-chaarted-nejm-2015","kind":"paper","name":"CHAARTED: chemohormonal therapy in metastatic hormone-sensitive prostate cancer","route":"/key-papers/paper-chaarted-nejm-2015/"},{"id":"paper-gravis-getug-afu-15-docetaxel-lancet-oncol-2013","kind":"paper","name":"GETUG-AFU 15: androgen deprivation alone or with docetaxel in non-castrate metastatic prostate cancer","route":"/key-papers/paper-gravis-getug-afu-15-docetaxel-lancet-oncol-2013/"},{"id":"paper-stampede-abiraterone-nejm-2017","kind":"paper","name":"STAMPEDE: adding abiraterone to hormone therapy at diagnosis of advanced prostate cancer","route":"/key-papers/paper-stampede-abiraterone-nejm-2017/"}],"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":"chemotherapy","kind":"section","name":"Chemotherapy","route":"/fronts/chemotherapy/"},{"id":"hormonal","kind":"section","name":"Hormonal Therapy","route":"/fronts/hormonal/"}],"drug":[{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"id":"zoledronic-acid","kind":"drug","name":"Zoledronic acid","route":"/drugs/zoledronic-acid/"}],"term":[{"id":"adt","kind":"term","name":"Androgen deprivation therapy (ADT)","route":"/terms/adt/"},{"id":"bone-metastases","kind":"term","name":"Bone metastases and skeletal-related events","route":"/terms/bone-metastases/"},{"id":"hazard-ratio","kind":"term","name":"Hazard ratio (HR)","route":"/terms/hazard-ratio/"}],"person":[{"id":"christopher-sweeney","kind":"person","name":"Christopher J. Sweeney","route":"/people/christopher-sweeney/"},{"id":"karim-fizazi","kind":"person","name":"Karim Fizazi","route":"/people/karim-fizazi/"},{"id":"nicholas-james","kind":"person","name":"Nicholas James","route":"/people/nicholas-james/"}],"bottleneck":[{"id":"b-negative-results","kind":"bottleneck","name":"Failures are hidden","route":"/bottlenecks/b-negative-results/"},{"id":"b-knowledge-diffusion","kind":"bottleneck","name":"Knowledge reaches practice too slowly","route":"/bottlenecks/b-knowledge-diffusion/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"journal":[{"id":"lancet-oncology","kind":"journal","name":"The Lancet Oncology","route":"/journals/lancet-oncology/"}]}}