Men with high-risk prostate cancer (PCa) accompanied by low PSA levels may survive longer by undergoing radical prostatectomy (RP) rather than radiation therapy, according to a new study.

Using data from the Surveillance, Epidemiology and End Results (SEER) database, investigators identified 9114 men with Gleason 8 to 10 PCa and PSA levels of 10 ng/mL or less. To date, no uniform treatment standard exists for this group of patients, they noted.

Of the 9114 patients with Gleason 8 to 10 PCa and PSA levels of 10 ng/mL or less identified using the Surveillance, Epidemiology and End Results (SEER) databases, 4175 underwent RP, 4114 received external beam radiation therapy (EBRT), and 825 received EBRT plus brachytherapy (EBRT + BT). The study population had a median follow-up duration of 47 months.

Compared with RP, external beam radiation therapy (EBRT) and EBRT plus brachytherapy (EBRT+BT) were significantly associated with an approximately 3.4-fold and 2.1-fold increased risk of death from any cause, respectively, in adjusted analyses, Yadong Guo, MD, and colleagues at Tongji University in Shanghai, China, reported in Frontiers in Oncology. EBRT was significantly associated with a nearly 2.5-fold increased risk of PCa-specific mortality compared with RP. The risk of PCa-specific mortality did not differ significantly between RP and EBRT+BT. In addition, RP and EBRT+BT were associated with similar survival among men older than 70 years or those who had PSA levels of 2.5 ng/mL or less. The investigators concluded that EBRT+BT could be an alternative option for these patients.

The 3-years OS rates were 98.4% for the RP group, 95.1% for the EBRT group, and 96.7% for EBRT+BT group, according to the investigators. The 5-year OS rates were 96.8%, 87.3%, and 92.8%, respectively. At 10-years, the OS rates were 67.5%, 58.0%, and 61.5%, respectively. 

The 3-year PCSM rate was 0.5% for the RP group, 1.4% for the EBRT group, and 0.8% for the EBRT+BT group. The 5-year PCSM rates were 1.4%, 4.8%, and 2.3%, respectively. The 10-year PCSM rates were 16.3%, 23.7%, and 6.5%, respectively.

Commenting on the new study, Amar U. Kishan, MD, Assistant Professor of Radiation Oncology at the University of California, Los Angeles, told Renal & Urology News: “While high-grade tumors that produce low amounts of PSA are likely to be more aggressive, there are important limitations in using population databases like the SEER registry in terms of answering questions about comparative effectiveness. For instance, it does not include data on duration of androgen deprivation therapy given with radiation, which we know is critical.”

Bruce Jacobs, MD, MPH, Assistant Professor of Urology at the University of Pittsburgh School of Medicine, said the study is important because a trial with men randomized to these 3 different treatments is not possible. “So, we have to have other ways to get at the answer,” Dr Jacobs said. “You have to account for selection bias. Radiation patients tend to be similar, but when you have surgery versus radiation, then you become concerned that the patients are different. So with observational studies you have to keep that in mind.”

David Penson, MD, Professor of Urologic Oncology at Vanderbilt University in Nashville, Tennessee, said that, in his opinion, urologists will learn little from the new study. He said he thinks the reported findings are largely influenced by bias. “The problem with these studies is that you are asking data to do things it can’t,” Dr Penson said. For example, the SEER database, which collects data from state cancer registries, does not collect any information on how sick the patient is.

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Zachary L. Smith, MD, Assistant Professor of Surgery at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, Missouri, said this study has some strengths, but many weaknesses as well. For one, the study must be viewed cautiously because it lacks information on dosage or administration details of the radiation used in the men who received EBRT and EBRT+BT as well as details on the use of androgen deprivation therapy (ADT). Further, it lacks information on additional local therapy men may have received following relapse.

“One reason these high-risk patients tend to fare a little better after prostatectomy in many studies is because they can still get radiation later if they have recurrence,” Dr Smith said. After radiotherapy, he added, so few urologists are willing to perform salvage prostatectomy that patients often only get ADT.  “This information is not accounted for in the current study, he said.

Reference

Guo Y, Mao S, Zhang A, et al. Survival significance of patients with low prostate-specific antigen and high-grade prostate cancer after radical prostatectomy, external beam radiotherapy, or external beam radiotherapy with brachytherapy. Front Oncol. 2019.

doi: 10.3389/fonc.2019.0068