Better Outcomes With RT for Black Prostate Cancer Patients

Roxanne Nelson, RN, BSN

October 23, 2018

SAN ANTONIO — Population-based studies have suggested that, compared with white men, black men are at higher risk of dying from prostate cancer. However, a new analysis shows that black men may achieve comparatively higher cure rates when treated with radiation therapy.

This is the first study demonstrating improved prostate cancer outcomes for this population compared with whites.

"Black men are more likely to die of prostate cancer than white men in the USA, and black race is an independent prognostic factor for poor outcomes," said lead author Daniel Spratt, MD, an associate professor and chief of the Genitourinary Radiotherapy Program at the University of Michigan Rogel Cancer Center, Ann Arbor. "When we started this project, we had the commonly held assumption that black men harbor more aggressive disease that leads to lower survival rates."

Their data show, however, that this assumption may not be true.

He explained that stage-for-stage disparities in prognosis between black and white men with prostate cancer are primarily driven by social/cultural factors. "However, a subset of black men with prostate cancer have distinct biology that may favor treatment with radiation therapy," said Spratt.

Spratt presented his findings during the plenary session at the American Society for Radiation Oncology (ASTRO) 2018.

In a discussion of the findings, Richard Den, MD, associate professor of radiation oncology, cancer biology, and urology at the Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, provided listeners with a takeaway message.

"Overall, these data suggest that race should not alter the approach to prostate cancer," Den concluded. "Regardless of their race, we should treat patients based on the stage and characteristics of their tumor. If a patient is black, he should not get intensified treatment or de-intensified treatment."

Some Context

Compared with white men, there is a 60% higher incidence of prostate cancer among black men, and the disease-specific mortality rate is more than two-times greater.

The reasons for these disparities are complex and multifactorial. These include racial bias in treatment, socioeconomic issues, insurance, and disparities in access to care. However, data also suggest that there may be important intrinsic biological differences between races. For example, prostate cancer is diagnosed, on average, about 5 years earlier in blacks than whites.

However, in the new study, when investigators adjusted for nonbiological factors, the differences between races disappeared, Spratt explained. "We looked at biologic differences that could influence treatment sensitivity, not just at the biologic differences between races."

Increased Radiosensitivity

In this two-part study, Spratt and colleagues investigated the interplay of androgen-receptor (AR) activity and radiotherapeutic sensitivity, with the goal of providing a molecular rationale that could help explain the disparity in outcomes.

First, they investigated differences in gene expression in tumor samples from 17,003 men (1953 or 11.5% were black men) with prostate cancer and found that tumors from black men had lower AR activity and DNA-repair expression.

Tumors with low AR activity were significantly more likely to develop distant metastases within a 10-year period (37% vs 17%; P = .008), and low AR activity was an independent predictor of distant metastasis. This association remained even after adjusting for characteristics that included Gleason grade, T-stage, prostate-specific antigen (PSA) level, margin status after surgery, and lymph node invasion (P = .03).

Their tumors also had decreased expression of the double-strand DNA repair pathway (P < .001), increased expression of immune pathways (P < .001), and increased radiosensitivity as predicted by a 24-gene prostate cancer radiation sensitivity score that was developed by Spratt and his team.

This increase in radiotherapeutic sensitivity suggests that black patients with prostate cancer will have better outcomes with radiation therapy, Spratt explained.

In the second part of the study, transcriptome-wide expression profiles and clinical radiosensitivity were examined in tumor samples that were obtained from 5854 patients (1129 black men) who participated in four large NRG Oncology/RTOG randomized prostate cancer trials (NRG-RTOG 9202, 9408, 9413, and 9910). Competing risk adjustments were used for all survival analyses for biochemical recurrence and distant metastases.

This meta-analysis showed that black men have lower rates of biochemical recurrence and metastatic disease compared with white men, explained Spratt.

Among black patients with prostate cancer, the rates of biochemical cancer recurrence (hazard ratio (HR), 0.82; 95% CI, 0.74, 0.92; P = .0005) and distant metastasis (HR, 0.70; 95% CI, 0.57, 0.86; P = .0008) were reduced, even after controlling for confounders such as age, performance status, PSA, Gleason grade, T-stage, N-stage, and hormone therapy use.

"We show that a subset of black men with prostate cancer does have a distinct biology that may favor treatment with radiation," Spratt concluded.

But the most important message from this presentation, he emphasized, is that when population registry data such as SEER show that black patients have worse outcomes, this can change if the social disparities are minimized and these patients are analyzed in the context of a randomized clinical trial. "Not only do they have potential equal outcomes, we show they have significantly improved outcomes with radiation therapy," he added.

Other New Data About Black Men

Meeting discussant Den noted that through the use of randomized controlled trials, new data have been able to emerge regarding black men and prostate cancer. He emphasized that the cohort had a high proportion of black men enrolled, as well as a high proportion with high-risk disease.

Rather than having poorer outcomes, "remarkably, we found the opposite to be true," said Den. "Black men had a statistically lower rate of distant metastases as well as prostate cancer-specific mortality."

Distant metastases, in the context of prostate cancer, have been shown to be a "bonafide surrogate for overall survival," he explained. "So that could mean that black men treated with radiation therapy may live longer than their white counterparts."

The study does have limitations, he noted, such as if these data can be generalized to the entire US and international populations. "I would argue that the answer is yes," he said. "The difference in biology is hypothesis generating and not conclusive, and it challenges us to generate more trials to truly address these underlying challenges."

Den also pointed out that these data were the result of a single biopsy, and as there is significant heterogeneity in the prostate itself, it is unknown if these results would be altered if multiples sites had been used.

Spratt has reported no relevant financial relationships. Den has disclosed relationships with Bayer and GenomeDx, and is a committee member for NRG Oncology GU.

American Society for Radiation Oncology (ASTRO) 2018. Abstract 4, presented October 23, 2018.

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