JAMA Oncology has published a new study that suggests that adding a statin drug at the initiation of hormone therapy (ADT) to the treatment protocol for a man with progressive, hormone-sensitive prostate cancer may significantly impact their actual time to disease progression (TTP).
Historically, we know Statin use has been associated with improved prostate cancer outcomes. It is believed that the biology behind the positive effect of statin drugs is directly related to the fact that Dehydroepiandrosterone sulfate (DHEAS) is a precursor of testosterone (which feeds prostate cancer) and a substrate for SLCO2B1, an organic anionic transporter (moving substances into the cell).
Additionally, it has been shown that genetic variants of SLCO2B1 correlate with time to progression (TTP) dwhile men have androgen deprivation therapy (ADT). Statin drugs also use the anionic transporter SLCO2B1 to enter cells, and thus may compete with DHEAS uptake by the tumor cells, limiting their androgen uptake.
The researchers retrospectively analyzed 926 men who were hormone sensitive and who had received ADT for biochemical or metastatic recurrence.
The first determined whether statins interfere with DHEAS uptake. Then they queried their institutional clinical database to assess for an association between statin use and TTP during ADT using multi-variable Cox regression analysis and adjusted for known prognostic factors.
They confirmed that statins did block DHEAS uptake by competitively binding to SLCO2B1 inn the ADT cohort of men taking a statin at ADT initiation.
After a median follow-up of 5.8 years, 70% of the men had experienced disease progression while receiving ADT.
Median TTP during ADT was 20.3 months. Men taking statins had a longer median TTP during ADT compared with nonusers (27.5 [95% CI, 21.1-37.7] vs 17.4 [95% CI, 14.9-21.1] months; P?<?.001). The association remained statistically significant after adjusting for predefined prognostic factors (adjusted hazard ratio, 0.83 [95% CI, 0.69-0.99]; P?=?.04).
The researchers also noted that the positive statin effect was observed for both men with and without metastases.
They concluded that Statin use at the time of ADT initiation was associated with a significantly longer TTP during ADT even after adjustment for known prognostic factors. They also found that for men taking statins, statins competitively reduce DHEAS uptake by the cancer cells, thus effectively decreasing the available androgens making their way into the cells.
The data for this study was derived from a retrospective analysis. They initial studies from which the data was taken were not designed to look at these questions, so the conclusions and suggestions must be verified by having a properly designed trial.
This study only looked at the use of statins at the beginning of ADT. It did not evaluate adding statins to already “on-going” ADT.
JAMA Oncol. Published online May 07, 2015. doi:10.1001/jamaoncol.2015.0829: Statin Use at the Time of Initiation of Androgen Deprivation Therapy and Time to Progression in Patients With Hormone-Sensitive Prostate: Lauren C. Harshman, MD; Xiaodong Wang, PhD; Mari Nakabayashi, MD; Wanling Xie, MS; Loana Valenca, MD; Lillian Werner, MS; Yongjiang Yu, PhD; Aaron M. Kantoff, BS; Christopher J. Sweeney, MBBS; Lorelei A. Mucci, ScD; Mark Pomerantz, MD; Gwo-Shu Mary Lee, PhD; Philip W. Kantoff, MD