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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.
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.
This 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.
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.
Men diagnosed with prostate cancer that has already spread, or that is locally advanced and high risk, should start abiraterone (or another androgen-receptor pathway inhibitor) at the same time as testosterone suppression rather than waiting for resistance. This roughly halves the risk of death over several years. The same platform later showed that docetaxel chemotherapy and, in high-volume metastatic disease, triple therapy also help, and that abiraterone benefits men with high-risk disease treated with radiotherapy.
This is the paper Europe PMC returns for registry id NCT00268476 with the most citations, so it is the natural first reading for anyone following the STAMPEDE trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
Docetaxel with androgen deprivation is a standard for high-volume metastatic hormone-sensitive prostate cancer, now usually combined with an androgen receptor pathway inhibitor as triplet therapy.
A negative trial that was later overturned, and a standing argument for pooling individual trials rather than acting on the first one to report. It is also the reason the distinction between high-volume and low-volume metastatic disease is written into guidelines.
Shares CHAARTED: chemohormonal therapy in metastatic hormone-sensitive prostate cancer, Nicholas James, Hazard ratio (HR), 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 and the tag prostate-evidence.
Shares Androgen deprivation therapy (ADT), Hazard ratio (HR), Metastatic hormone-sensitive prostate cancer, 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 and the tag prostate-evidence.
Shares Androgen deprivation therapy (ADT), Metastatic hormone-sensitive prostate cancer, 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, Prostate cancer and the tag prostate-evidence.
Shares Hazard ratio (HR), 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, Docetaxel, Prostate cancer and the tag prostate-evidence.
Shares Karim Fizazi, 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, Docetaxel, Prostate cancer and the tag prostate-evidence.
Shares Androgen deprivation therapy (ADT), 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, Prostate cancer and the tag prostate-evidence.
Shares Karim Fizazi, 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, Prostate cancer and the tag prostate-evidence.
Shares Androgen deprivation therapy (ADT), Metastatic hormone-sensitive prostate cancer, 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, Prostate cancer and the tag prostate-evidence.