Better results with RT for black patients with prostate cancer

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

This is the first study showing improved prostate cancer outcomes for this population compared to whites.

"In the United States, black men are more likely to die of prostate cancer than white men, and the black race is an independent prognostic factor for poor results," said lead author Daniel Spratt, MD , associate professor and head of the genitourinary radiotherapy program at the Rogel Cancer Center at the University of Michigan, Ann Arbor. "When we started this project, we started from the common principle that black men harbor a more aggressive disease that leads to lower survival rates."

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

He explained that the disparities between the prognosis stages of black and white men with prostate cancer are mainly due to sociocultural factors. "However, a subgroup of black men with prostate cancer has a distinct biology that could promote radiotherapy treatment," Spratt said.

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

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

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

A bit of context

Compared to white men, the incidence of prostate cancer is 60% higher among black men and the death rate by disease is more than twice as high.

The reasons for these disparities are complex and multifactorial. These include racial bias in treatment, socio-economic problems, insurance and disparities in access to care. However, the data also suggest that there could be significant intrinsic biological differences between breeds. For example, prostate cancer is diagnosed on average about 5 years earlier in blacks than in whites.

However, in the new study, when researchers adjusted to non-biological factors, differences between breeds disappeared, Spratt explained. "We looked at the biological differences that can affect the sensitivity to treatment, not just the biological differences between races."

Increased radiosensitivity

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

First, they studied the differences in gene expression in tumor samples of 17,003 men (1953 or 11.5% were black men) with prostate cancer and found that black men's tumors had lower AR activity and weaker DNA repair expression.

Tumors with low RA activity were significantly more likely to develop distant metastases over a 10-year period (37% vs. 17%; P = 0.008), and low AR activity was an independent predictor of distant metastasis. This association remained even after adjustment for features such as Gleason grade, T stage, prostate specific antigen level (PSA), margin status after surgery, and l 39; invasion of the lymph nodes (P = 0.03).

Their tumors also exhibited decreased expression of the double-stranded DNA repair pathway (P <0.001), increased expression of immune pathways (P <0.001) and increased radiosensitivity, as predicted by a 24-gene prostate cancer sensitivity score developed by Spratt and his team.

This increase in radiotherapeutic sensitivity suggests that black patients with prostate cancer will get better results with radiotherapy, explained Spratt.

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

This meta-analysis showed that black men had lower rates of biochemical recurrence and metastasis than white men, Spratt explained.

In black patients with prostate cancer, recurrence rates of biochemical cancer (relative risk (RSS), 0.82, 95% CI, 0.74, 0.92; P = 0.0005) and distant metastases (HR, 0.70, 95% CI, 0.57, 0.86; P = 0.0008) were reduced even after controlling for confounding factors such as age, performance status, PSA, Gleason grade, T stage, N stage and use of a hormonal treatment.

"We show that a subgroup of black men with prostate cancer has a distinct biology that could promote radiation treatment," concluded Spratt.

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

Other new data on black men

The presenter of the meeting, Den, noted that through the use of randomized controlled trials, new data could emerge regarding black men and prostate cancer. He pointed out that the cohort had a high proportion of black men enrolled, as well as a high proportion of people at high risk.

Rather than having poorer results, "remarkably, we found that the opposite was true," said Den. "Black men had a statistically lower rate of distant metastases and mortality from prostate cancer."

Remote metastasis, in the context of prostate cancer, has proven to be a "good faith substitute for overall survival," he said. "This could mean that black men treated with radiotherapy could live longer than their white counterparts."

The study has limitations, he noted, especially if these data can be generalized to the entire American and international population. "I would say the answer is yes," he said. "The difference in biology is leading to hypotheses and is not conclusive, and it encourages 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 that because of the high heterogeneity of the prostate itself, it is unclear whether these findings could be altered if multiple sites had been used.

Spratt has not reported any relevant financial relationship. Den has disclosed his relationship with Bayer and GenomeDx and is a member of the NRG Oncology GU committee.

American Radiation Oncology Society (ASTRO) 2018. Abstract 4, submitted on October 23, 2018.

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