African American men with prostate cancer that meets current criteria for very low-risk disease might actually be harboring larger and more aggressive tumors that make active surveillance a less viable option, according to the results of a study published online in the Journal of Clinical Oncology1 (JCO) and reported in the public and medical press.
“This study offers the most conclusive evidence to date that broad application of active surveillance recommendations and associated outcomes may not be suitable for African Americans,” stated the study’s corresponding author, Edward M. Schaeffer, MD, PhD, Associate Professor of Urology and Oncology at the Johns Hopkins University School of Medicine in Baltimore, Co-Director of the Prostate Cancer Multidisciplinary Clinic at the Johns Hopkins Hospital, and Director of Global Urologic Services for Johns Hopkins Medicine International.
“What we learned in doing this study,” Dr. Schaeffer told The ASCO Post, “is that most active surveillance protocols from large institutions and most active surveillance studies have a limited number of non-Caucasian patients.” The study “supports earlier studies that suggested the outcomes for African American men are not equivalent to the outcomes for Caucasian men in active surveillance, or put another way, outcomes for African American men with very low-risk prostate cancer are not equivalent to Caucasian men with very low-risk prostate cancer,” he said.
More Adverse Pathology
The study involved 1,801 men (1,473 white men, 256 African American men, and 72 others) who met National Comprehensive Cancer Network (NCCN) criteria for very low-risk prostate cancer.3 “These were men who would be candidates for active surveillance but chose an active intervention with surgery. That is important to be clear about,” Dr. Schaeffer stressed.
Preoperative characteristics among the men were similar, although African American men had slightly worse Charlson comorbidity scores. Because the men did have surgery, investigators were able to evaluate pathologic findings and oncologic outcomes. What they found was that African American men considered to be at very low-risk of prostate cancer had more adverse pathologic features at the time of radical prostatectomy and poorer oncologic outcomes.
African American men had a lower rate of organ-confined cancers (87.9% vs 91.0% for white men, P = .004) and a higher rate of positive surgical margins (9.8% vs 5.9%, P = .02). African American men were more likely to have disease upgrading (27.3% vs 14.4% for white men, P < .001).
“Furthermore, African Americans demonstrated a significantly higher hazard of biochemical recurrence [4.0% vs 1.4%, log-rank P = .004],” according to the study report, and adverse pathologic findings were more common in African American patients (14.1% vs 7.7% for white patients, P = .001). “On multivariable analysis, [African American] race was an independent predictor of adverse pathologic features [odds ratio [OR] = 3.23, P = .03] and pathologic upgrading [OR = 2.26, P = .03],” the investigators reported.
Survival Differences Anticipated
At a median follow-up of 3 years (2 years for African American patients and 4 years for white patients), there were no differences in metastasis-free, cancer-specific, or overall survival, but Dr. Schaeffer noted that longer follow-up is needed. The Cancer of the Prostate Risk Assessment Post-Surgical scoring system (CAPRA-S) score “assesses the likelihood of the cancer coming back, and CAPRA-S scores are statistically higher in African American men than in Caucasians,” he said.
CAPRA-S is “a validated predictor of biochemical recurrence that ranges from 0 to 12 points based on serum PSA, pathologic Gleason pattern, lymph node involvement, extracapsular extension, seminal vesicle invasion, and positive surgical margins. We defined increased/higher recurrence risk in this cohort as a CAPRA-S ≥ 3, which is associated with a 27.2% or higher 5-year risk of recurrence,” the investigators explained in the study report. The results showed that a CAPRA-S > 3 was significantly higher in African American men (14.8% vs 6.9% for white men, P < .001).
“So I would anticipate that we would over time see more cases of metastases in the African American cohort, and we didn’t see them because our follow-up was not long enough to capture those events,” Dr. Schaeffer said.
More Anterior Tumors
In another study, published simultaneously, Dr. Schaeffer’s research team performed a detailed pathologic analysis of the men in the JCO paper.2 Detailed examination of surgical specimens showed that African American men had higher total tumor volume than white men, were more likely to have multiple tumor nodules, and more likely to have the dominant nodule located in the anterior aspect of the prostate gland. “That anterior location is not easily sampled by a standard prostate biopsy,” Dr. Schaeffer noted.
“In the African American men, the tumors were in an entirely different location than in the Caucasian men,” he said. “We believe that there is a biologic reason for this anatomic difference. Our research team is actively exploring several potential mechanisms.”
Based on these findings, “we are working on understanding biologically why these tumors develop in a different locations as well as on potential modifications to biopsy templates for African American men,” Dr. Schaeffer said.
Not Universal Rejection
Dr. Schaeffer noted that since the study published in JCO “is a retrospective analysis from a single institution, the results should not support universal rejection of active surveillance, but rather, should promote further studies to address whether alternate modes of race-specific surveillance should be used to ensure parity.” He said that he has shared findings with a prostate cancer active surveillance group at the University of California, San Francisco, and “they are investigating whether or not these observations hold true in their group as well.”
Dr. Schaeffer also credited colleagues from the University of Miami. “They were the first people to report on African American men in active surveillance, and they have shown similar findings, although it was in a small number of men,” he said.
“I think this study certainly suggests that differing outcomes for men with prostate cancer of different races should really be explored more,” Dr. Schaeffer stated. “We are not saying that this is something that should universally be adopted, but we really look forward to and are encouraged by other investigators confirming our results.” ■
Disclosure: Dr. Schaeffer reported no potential conflicts of interest.
References
1. Sundi D, Ross AE, Humphreys EB, et al: African American men with very low–risk prostate cancer exhibit adverse oncologic outcomes after radical prostatectomy: Should active surveillance still be an option for them? J Clin Oncol. June 17, 2013 (early release online).
2. Sundi D, Kryvenko ON, Carter HB, et al: Pathologic examination of radical prostatectomies in men with very low-risk disease at biopsy reveals distinct zonal distribution of cancer in African American men. J Urol. June 13, 2013 (early release online).
3. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Prostate cancer, version 4.2013. Available at www.nccn.org. Accessed August 14, 2013.
