Wenzel M, Nocera L, Ruvolo CC et al: Racial/ethnic disparities in tumor characteristics and treatments in favorable and unfavorable intermediate risk prostate cancer. J Urol 2021; 206: 69.

Intermediate risk (IR) prostate cancer (PCa) represents the largest subgroup of patients with localized PCa and exhibits the most heterogeneity in its cancer make-up.^1-4 In patients with IR PCa, baseline characteristics such as prostate specific antigen (PSA), clinical T-stage, biopsy Gleason grade group (GGG) and percentage of positive biopsy cores may vary across a wide range of values.²

Based on potential heterogeneity of baseline PCa characteristics, despite attempts at risk level standardization, clinicians may recommend active treatment in the form of either radical prostatectomy (RP) or external beam radiotherapy (EBRT) to different proportions of patients. The phenomenon of active treatment assignment variability was previously reported.⁵ Specifically, the authors investigated the use of EBRT vs RP according to the specialty of treating physicians (urologist and radiation oncologist) and found higher rates of RP among urologists. Conversely, higher rates of EBRT were found among radiation oncologists. Such phenomena could be suggestive of random variability in active treatment assignment. However, to the best of our knowledge, variability in active treatment rates has not been examined according to patient race/ethnicity. We hypothesized that race/ethnicity may represent an important determinant of active treatment in IR PCa patients. To offset some of these differences, we stratified patients according to the National Comprehensive Cancer Network® (NCCN®) favorable and unfavorable IR criteria.

In the current study, we relied on the Surveillance, Epidemiology, and End Results (SEER) 18 database (2010—2015) and identified patients with histologically confirmed adenocarcinoma of the prostate diagnosed at biopsy.⁶ Racial/ethnic groups were defined as Caucasian, African American, Hispanic or other racial/ethnic groups. Clinically favorable and unfavorable IR PCa was stratified according to NCCN guidelines.⁴ Active treatment was defined as either RP or EBRT monotherapy.

In the first part of the analyses, we focused on patients with favorable IR PCa. Here, we tabulated active treatment rates without adjustment for baseline age and PCa characteristics (PSA, clinical T-stage [cT1 vs cT2], GGG [GGG 1 vs GGG 2 vs GGG 3], percentage of positive biopsy cores). Thereafter, we tabulated active treatment rates after full adjustment for baseline age and PCa characteristics. Similarly, we repeated all of the above steps in patients with unfavorable IR PCa. Finally, log linear regressions were used to compute estimated annual percent change (EAPC) in active treatment modalities according to race/ethnicity without and with the above-mentioned adjustment for baseline age and PCa characteristics.

Of 22,621 patients with favorable IR PCa, Caucasians accounted for 72.3% vs African Americans for 18.4% vs Hispanics for 8.9%. Of 23,554 unfavorable IR PCa patients, Caucasians accounted for 70.8% vs African Americans for 20.3% vs Hispanics for 8.9%.

We observed important heterogeneity in rates of RP and EBRT in patients with favorable (fig. 1) and unfavorable IR PCa according to racial/ethnic groups. Specifically, RP rates were highest in favorable and unfavorable IR PCa in Caucasians (41.8% and 43.9%), followed by Hispanics (40.2% and 42.2%) and African Americans (31.7% and 33.4%), respectively. Conversely, EBRT rates in favorable and unfavorable IR PCa were highest in African Americans (31.0% and 35.5%), followed by Hispanics (28.3% and 32.5%) and Caucasians (26.3% and 30.9%), respectively.

Figure 1. Stacked bar plots depicting treatment type distribution in overall cohort, Caucasians, African Americans (AA) and Hispanics in favorable (A) and unfavorable (B) IR PCa. Brachy, brachytherapy. NLT, no local treatment.

After adjustment for baseline age and PCa characteristics (PSA, cT-stage, GGG, percentage of positive biopsy cores), absolute RP rate difference decreased between racial/ethnic groups from an unadjusted value of 10.1% to 4.3% in favorable IR PCa and from an unadjusted value of 10.5% to 5.6% in unfavorable IR PCa (fig. 2). Similarly, observations were made for EBRT.

Figure 2. Stacked bar plots depicting adjusted (for age, PSA, clinical T stage, GGG and percentage of positive biopsy cores) treatment type distribution in overall cohort, Caucasians, African Americans (AA) and Hispanics in favorable (A) and unfavorable (B) IR PCa. Brachy, brachytherapy. NLT, no local treatment.

In temporal trends analyses (fig. 3) of Caucasians, RP represented the most common active treatment modality. Its rate decreased from 45.4% to 39.0% in favorable IR PCa (p <0.01). However, such a decrease was not reported in unfavorable IR PCa (45.6% to 43.8%, p=0.3). Conversely, in African Americans, EBRT initially represented the most common active treatment modality. Its rate decreased from 32.2% to 28.5% (p=0.047) in favorable IR PCa. However, such a decrease was not reported in unfavorable IR PCa (36.4% to 34.8%, p=0.7). Finally, in Hispanics, RP also represented the most frequent active treatment modality. Its rate did not change in either favorable IR PCa (40.8% to 42.6%, p=0.5) or unfavorable IR PCa (43.1% to 42.2%, p=0.3).

Figure 3. Unadjusted trends over time in favorable and unfavorable IR PCa from 2010 to 2015 depicting changes in treatment rates. Log linear regression analyses were used to compute EAPC for favorable IR PCa in Caucasians (A), favorable IR PCa in African Americans (B), favorable IR PCa in Hispanics (C), unfavorable IR PCa in Caucasians (D), unfavorable IR PCa in African Americans (E), unfavorable IR PCa in Hispanics (F). Brachy, brachytherapy. NLT, no local treatment.

Figure 4. Trends over time in favorable and unfavorable intermediate risk IR PCa from 2010 to 2015 depicting changes in treatment rates after adjustment for baseline age and PCa characteristics. Log linear regression analyses were used to compute EAPC after adjustment for PCa characteristics for favorable IR PCa in Caucasians (A), favorable IR PCa in African Americans (B), favorable IR PCa in Hispanics (C), unfavorable IR PCa in Caucasians (D), unfavorable IR PCa in African Americans (E), unfavorable IR PCa in Hispanics (F). Brachy, brachytherapy. NLT, no local treatment.

In Caucasians, after adjustment for baseline age and PCa characteristics, the absolute RP rate difference over time in favorable IR PCa was 0.9% (fig. 4). In unfavorable IR PCa, the absolute RP rate difference over time was 1.4%. A similar phenomenon that exhibited no or marginal absolute treatment rate differences over time was also observed in African Americans or Hispanics.

Taken together, the heterogeneity in overall treatment rates according to race/ethnicity, as well as heterogeneity of active treatment rates over time that was recorded among the 3 examined racial/ethnic groups may indicate that race/ethnicity determines treatment assignment instead of PCa characteristics. However, after adjustment for differences in baseline age and PCa characteristics according to race/ethnicity, the differences in active treatment rates between race/ethnicity groups became marginal. Moreover, the differences in active treatment rates according to race/ethnicity over time disappeared. These observations are very important, and they emphasize the need for detailed baseline adjustment for age and PCa characteristics, especially when race/ethnicity is considered. Absence of adjustment may lead to severely biased interpretation. Specifically, in the current analysis, very important differences in RP rates distinguished Caucasians from African Americans. Similarly, EBRT rates distinguished African Americans from Caucasians and Hispanics. However, after adjustment for baseline age and PCa characteristics, these differences mostly vanished. In consequence, instead of incorrectly interpreting the differences in active treatment rates as race/ethnicity driven, it may be concluded that such differences directly and exclusively depend on baseline age and PCa characteristics.

Acknowledgment

Dr. Wenzel would like to acknowledge the authors of The Journal of Urology® article highlighted in this Journal Brief: Luigi Nocera, MD, Claudia Collà Ruvolo, MD, Christoph Würnschimmel, MD, Zhe Tian, MSc, Shahrokh F. Shariat, MD, PhD, Fred Saad, MD, PhD, Alberto Briganti, MD, PhD, Derya Tilki, MD, PhD, Markus Graefen, MD, PhD, Luis A. Kluth, MD, PhD, Philipp Mandel, MD, PhD, Felix K.H. Chun, MD, PhD and Pierre I. Karakiewicz, MD, PhD.