Population-Based Study Informs Decision-Making in Localized Prostate Cancer

Daniel A. Barocas, MD, MPH, FACS, an associate professor in the Department of Urology at Vanderbilt University Medical Center

Daniel A. Barocas, MD, MPH, FACS

Results of a recent study of patients with localized prostate cancer demonstrated an informed understanding of the varied survivorship experiences for those who undergo radical prostatectomy, radiation therapy, or active surveillance.

The population-based, prospective cohort Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) trial compared outcomes among patients with localized prostate cancer who underwent robot-assisted radical prostatectomy, intensity-modulated external beam radiation therapy (EBRT), and active surveillance. In the study, which accrued more than 3000 patients with diverse backgrounds in 2011 and 2012, investigators administered health-related quality of life (QoL) surveys to patients at regular intervals.

The primary endpoint was the Expanded Prostate Cancer Index Composite (EPIC-26), which measures disease-specific QoL in men with prostate cancer—assessing urinary incontinence, urinary obstructive/irritative symptoms, sexual function, bowel function, and symptoms related to hormonal therapy.

Results showed that patients who underwent surgery had a larger decline in sexual function compared with those who underwent EBRT or active surveillance, as well as a larger decline in urinary incontinence scores. Men who underwent EBRT had modest declines in urinary irritative and obstructive symptoms, while these scores did improve for those who had surgery.

"The study is big enough and we collected enough precise data early on that we can make personalized estimates of the functional outcomes," said lead study author Daniel A. Barocas, MD, MPH, FACS. 

Despite these significant differences between the 3 approaches noted in year 1, urinary irritative/obstructive, bowel function, and hormone therapy symptom scores attenuated over time.

Additional follow-up in CEASAR will explore the identification of disparities in the quality of radiation, different functional outcomes by race and disease severity, and lack of benefit of nerve-sparing surgery in those with poor baseline function. Moreover, a 5-year data update is pending publication and a 10-year analysis investigation has recently received funding, Barocas said.

In an interview during the 2019  OncLive^  State of the Science Summit^™ on Genitourinary Cancers, Barocas, an associate professor in the Department of Urology at Vanderbilt University Medical Center, discussed the CEASAR study in prostate cancer, as well as therapeutic updates in renal cell carcinoma. 

OncLive:  Could you highlight the CEASAR data in prostate cancer?

Barocas:  We have followed men longitudinally from diagnosis [with prostate cancer] in 2011 and 2012, and we administered self-reported questionnaires serially to them since then. 

Our main findings are essentially what we expected. Each treatment has its own profile of adverse events (AEs). For example, we worry about erectile dysfunction and urinary leakage with surgery. Similarly, with radiation, we worry about erectile dysfunction, although it appears to be a gradual decline with radiation compared with surgery. We also worry about urinary and bowel function symptoms with radiation; however, [those AEs] were surprisingly modest in this cohort. 

If you look in the long-term—we are now at 5 years—you find that many of these differences attenuate. Even with the active surveillance patients, sexual function goes down gradually with age, and some patients veer off into treatment. As you get farther out to 5 years, the sexual function outcomes look similar. 

Still, the surgery group has a higher risk of urinary incontinence in the long term. Approximately 15% of men report a moderate or [significant] problem with urinary incontinence after 5 years. 

One of the projects off of that main study is a nomogram, where patients can enter their own information and get a personalized estimate of their functional outcomes. That is particularly exciting.

In renal cell carcinoma (RCC), what data support the use of adjuvant TKI therapy?

The most compelling data come from the S-TRAC study, which showed a disease-free survival advantage for sunitinib (Sutent). We have to take those results with a grain of salt because there are other studies that do not show an advantage. 

There are some quality-of-life issues with sunitinib compared with placebo, so it's not a “slam dunk.” However, it is compelling, and it is something that we can pull out to people who are motivated to prevent recurrence. 

Thus far, we don't have any “home runs” in the immuno-oncology space for adjuvant therapy, but there may be more to come as studies mature. 

There is a neat trial that we have open at our center, which is looking at neoadjuvant nivolumab (Opdivo) plus adjuvant nivolumab; That seems like an interesting strategy.

 

Baracos DA, Penson DF. Functional recovery following primary treatment for prostate cancer: update from the CEASAR Study. Eur Uro Focus. 2019;pii:S2405-4569(19)30108-7. doi: 10.1016/j.euf.2019.04.001.