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Prostate Cancer Radiotherapy: Bone Metastatic Burden Linked to Survival

Metastatic prostate cancer cells.

In patients receiving radiotherapy for newly diagnosed metastatic prostate cancer, bone metastasis count and location are associated with overall and failure-free survival, according to an exploratory analysis of the phase 3 STAMPEDE trial.

"Prostate radiotherapy improves survival in men with low-burden metastatic prostate cancer," write the investigators in their publication in JAMA Oncology, led by first author Adnan Ali, MBBS, Clinical Research Fellow in the Division of Cancer Sciences at the University of Manchester in the United Kingdom. "However, owing to the dichotomized nature of metastatic burden criteria, it is not clear how this benefit varies with bone metastasis counts and metastatic site."

Dr. Ali and colleagues analyzed the treatment outcomes of 1,939 patients with newly diagnosed metastatic prostate cancer enrolled in the STAMPEDE trial after 122 patients were excluded for either nonconventional imaging or lack of centralized baseline bone scans. Patients were stratified by number and location of bone metastatic sites, with 82% of patients having bone metastases with or without additional nonregional lymph node (NRLN) metastases, 9% having only NRLN metastases (defined as M1a disease), and 9% having visceral or other metastases. Baseline metastatic sites were identified by conventional imaging with bone scans and computed tomography (CT) or magnetic resonance imaging (MRI). Patients were randomized to receive standard-of-care therapy, consisting of androgen deprivation therapy with or without docetaxel, or the standard of care in combination with prostate radiotherapy, consisting of 55 Gy in 20 daily fractions over four weeks or 36 Gy in six weekly fractions over six weeks. The primary end points were overall survival and failure-free survival.

At a median follow-up of 37 months, bone metastatic counts were significantly associated with overall and failure-free survival benefit from radiotherapy, with the greatest benefit in patients who had three or fewer bone metastases. Absolute improvement in estimated three-year overall survival occurred at a rate of 8.5% in patients with one metastatic site, 6.2% in those with two metastatic sites, and 5.8% in those with three metastatic sites, with the survival benefit decreasing continuously in patients who had four or more bone metastases. Estimated three-year failure-free survival rates had an absolute improvement of 21.5% in patients with one metastasis, 10.1% in those with two metastases, 14.2% in those with three metastases, and 8.8% in those with four metastases. Patients who had only NRLN sites or 3 or fewer metastatic sites with no visceral metastases derived a greater degree of survival benefit from radiotherapy (hazard ratio for overall survival, 0.62; hazard ratio for failure-free survival, 0.57) compared with those who had four or more bone metastatic sites, visceral metastases, or other sites (hazard ratio for overall survival, 1.08; hazard ratio for failure-free survival, 0.87).

"Bone metastatic burden based on conventional imaging is predictive of overall survival and failure-free survival benefit when prostate radiotherapy is added to standard of care in newly diagnosed metastatic prostate cancer. This beneficial effect is most pronounced in patients with up to three bone metastases… without visceral or other metastasis," conclude Dr. Ali and colleagues in their publication. "The criteria for low metastatic burden based on conventional imaging, predictive of survival benefit from prostate radiotherapy in men with newly diagnosed metastatic prostate cancer, should now also include men with M1a disease."

For More Information

Ali A, Hoyle A, Haran AM, et al (2021). Association of bone metastatic burden with survival benefit from prostate radiotherapy in patients with newly diagnosed metastatic prostate cancer: a secondary analysis of a randomized clinical trial. JAMA Oncol. [Epub ahead of print] DOI:10.1001/jamaoncol.2020.7857

Image credit: Yale Rosen. Licensed under CC BY-SA


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