Studies Challenge Common Treatment Strategies in Prostate Cancer

Stephen H. Culp, MD

Two recent studies have raised questions about current trends in prostate cancer (PC) treatment, one supporting the employment of a little-used strategy—direct treatment of the primary tumor in men who have metastatic PC at diagnosis— and the other challenging the common tactic of androgen-deprivation therapy in men with early prostate cancer.

Prostatectomy Improves Survival in Metastatic PC

Men who presented with stage IV prostate cancer and underwent radical prostatectomy experienced significantly longer overall survival (OS) than men in that population who did not have surgery, a recent large, retrospective study has found.

The study suggested that this nonstandard treatment is worth further consideration, its authors wrote.

Men in the study who were treated with brachytherapy had the next-best rate of survival, and those treated with neither surgery nor brachytherapy had the lowest survival rate. Men who did not have surgery or brachytherapy received androgen-deprivation therapy, which is considered standard treatment, in combination with docetaxel-based chemotherapy, for men diagnosed with metastatic PC, according to authors Culp et al.

The study included 8185 men who had stage IV prostate cancer at diagnosis and were listed in the Surveillance Epidemiology and End Results cancer database between 2004 and 2010. The men were divided into cohorts based on the type of treatment they received: 7811 men had no surgery or radiation; 245 underwent radical prostatectomy; and 129 were administered brachytherapy. Five-year OS and predicted disease-specific survival (DSS) were 67.4% and 75.8% in the prostatectomy group; 52.6% and 61.3% in the brachytherapy group; and 22.5% and 48.7% in the group that received neither of those therapies, the authors reported. Surgery and brachytherapy were each independently associated with decreased causespecific mortality (CMS) (P<.01), they found. The authors pointed out, though, that some characteristics increased CSM in those who received local therapy, including high-grade disease, age ≥ 70 years, and prostate-specific antigen ≥ 20 ng/mL.

A limitation to the study was that the authors lacked information on whether participants had other medical conditions that could have affected their mortality, or had undergone systemic therapy, the investigators disclosed.

"Based on this, we can formulate the hypothesis that treatment of the primary tumor does affect survival in patients with metastatic prostate cancer, and therefore trials should be initiated to further examine this as an option for metastatic prostate cancer,” said urologist Stephen H. Culp, MD, of the University of Virginia Cancer Center, in a press release.

The University of Virginia has launched such a trial, and Eastern Virginia Medical School is organizing one, the university announced in the release.

No Survival Advantage With ADT in Most Early Prostate Cancer

Androgen deprivation therapy (ADT), widely used in early prostate cancer although it is not a standard except in the metastatic setting, demonstrated no survival benefits overall in a recent study of more than 15,000 men with localized disease.

The institution where the study was conducted, Georgetown Lombardi Comprehensive Cancer Center, pointed out in a press release that risks associated with ADT include impaired cognition, heart disease, and diabetes, and said the study’s investigators argued that those adverse events mitigate “any clinical or policy rationale for use of primary androgen deprivation therapy in these men.”

While physicians may employ primary ADT in older men with a higher risk of disease progression as an alternative to watchful waiting, “using PADT by itself immediately after diagnosis in the hopes of limiting cancer’s progression does not extend survival, according to this study,” said its lead investigator, Arnold Potosky, PhD, professor of Oncology and director of Health Services Research at Georgetown Lombardi, in the press release.

The 15,170 men in the study, identified in cancer registries in three large health plans, had localized disease and had not undergone surgery or radiation. They were diagnosed between 1995 and 2008 and followed through December 2010. The study considered both all-cause and prostate cancer-specific mortality as endpoints.

Overall, primary ADT was not associated with a risk of all-cause mortality (hazard ratio [HR]=1.03; 95% CI, 0.89-1.19) or prostate cancer-specific mortality (HR=1.03; 95% CI, 0.89-1.19). The therapy was associated with a decreased risk of all-cause mortality, but not prostate cancer-specific mortality, in men who had a high risk of cancer progression (HR=0.88; 95% CI, 0.78-0.97).

"This study is the most comprehensive study on the effectiveness of PADT for men who forgo radiation and surgery for their localized prostate cancer, and it tells us there is no strong reason to use it in most patients," Potosky said. "We found only a small survival benefit for primary androgen deprivation therapy compared to no therapy in men diagnosed with higher-risk localized prostate cancer."

References

1. Culp SH, Schellhammer PF, Williams MB. Might men diagnosed with metastatic prostate cancer benefit from definitive treatment of the primary tumor? a SEER-based study. Eur Urol. 2013. pii:S0302-2838(13)01209-8.
2. Potosky AL, Haque R, Cassidy-Bushrow AE, et al. Effectiveness of primary androgendeprivation therapy for clinically localized prostate cancer. J Clin Oncol. 2014. Published online March 17, 2014.