Racial Disparity in the Utilization of Multiparametric MRI–Ultrasound Fusion Biopsy for the Detection of Prostate Cancer - Full Text Article

Black men have significantly higher incidence and are up to three times more likely to die of prostate cancer (PCa) than White men. Multiparametric magnetic resonance imaging-ultrasound fusion biopsy (FBx) has emerged as a promising modality for the detection of PCa. The goal of our study is to identify differences in utilization of FBx between Black and White men presenting with suspicion of PCa.

We performed a retrospective review of Black and White men who presented with suspicion of PCa and required biopsy from January 2014 to December 2018. Multivariate logistic regression analysis was done to study the influence of race on the utilization of FBx.

Six hundred nineteen (Black: 182, White: 437) men were included in the study. Forty-one out of 182 (22.5%) Black men underwent FBx compared with 225/437 (51.5%) of White men (P < 0.001). After adjusting for age, race, prostate-specific antigen level, digital rectal exam, family history of PCa and health insurance provider, Black race was found to be a significant negative predictor of obtaining FBx (OR:0.32, 95% CI: 0.21–0.51, P < 0.001). Black race stayed an independent negative predictor (OR: 0.36, 95% CI: 0.20–0.64, P < 0.001) in the cohort of patients who were biopsy naïve; however, although reduced, there was no significant difference in the cohort with a prior negative biopsy (OR: 0.51, 95% CI: 0.19–1.36, P = 0.179).

Although FBx is a superior modality for early detection of PCa, we found that Black men were less likely to undergo FBx when presenting with PCa suspicion. Further investigation is needed to evaluate if this difference is patient preference or if there are underlying socio-economic, cultural or provider biases influencing this disparity.

Introduction Multi-parametric magnetic resonance imaging (mpMRI) of the prostate is increasingly being utilized for the evaluation of men with clinical suspicion of prostate cancer (PCa). MpMRI-ultrasound fusion biopsy (FBx) of the prostate has emerged as an alternative to the standard 12-core systematic biopsy such that the increased diagnostic accuracy allows for superior pathologic stratification of PCa. The use of FBx in the setting of prior negative prostate biopsy has been studied extensively1, 2 and significantly increased the ratio of detection of clinically significant (CS) to clinically insignificant disease.

Despite advancements in diagnostic testing for PCa, there remain distinct discrepancies in the diagnosis, treatment and outcomes between Black and White men with a new diagnosis of PCa. The importance of these findings cannot be understated as observational studies have found that Black men present at a younger age and with a more advanced stage of PCa compared with White men.4, 5 Furthermore, genomic and population-based analyses suggest an increased mortality risk for Black patients with lowrisk PCa that would otherwise be amenable to active surveillance,6, 7 albeit with an etiologic component of underdiagnosis. Importantly, the difference in PCa mortality between the two cohorts continues to be one of the largest of any cancer diagnosis.8 It remains to be found if the racial disparity in the diagnosis between Black and White men continues to persist in the utilization of mpMRI and FBx to augment PCa diagnosis. In the following study, we present a single-institutional review of Black and White men without any prior diagnosis of PCa to determine if disparity exists in the utilization of FBx for the tissue diagnosis of PCa between the two cohorts.

Materials and methods
Study population

The institutional review board approved this retrospective study and waived the informed consent requirement. The study was compliant with the Health Insurance Portability and Accountability Act of 1996. We performed a retrospective review of 829 patients undergoing either systematic biopsy alone or in combination with FBx from January, 2014 to December, 2018 at our institution. Eightyfive men with a Prostate-specific antigen level (PSA) > 20 ng/dl were excluded as they were more likely to go straight to SBx due to high PSA levels. A total of 619 Black and White men without a diagnosis of PCa, i.e., men who were prostate biopsy naïve or had a history of prior negative biopsy, were included in the final quantitative analysis (Fig. 1).


Fig. 1 Study population inclusion and exclusion criteria. Eight hundred twenty-nine patients presented for prostate biopsy. Eighty-five patients were excluded due to a PSA >20ng/dl, 104 were excluded due to a pre-existing prostate cancer diagnosis, and 21 patients were excluded that did not identify as White or Black. The final analysis included 619 patients (182 Black and 437 White). PSA prostatespecific antigen, DRE digital rectal exam.

Study data
Patient demographic, clinical, pathologic, and medical insurance data were recorded. Health insurance coverage was grouped into four broad categories: commercial, Medicare, Medicaid, or other/uninsured. Histopathological results of the prostate biopsy were grouped into the following three categories for the purpose of analysis: low-risk disease was defined as Gleason score (GS) of 3 + 3 (Grade Group 1), intermediate-risk as GS of 3 + 4 (Grade Group 2) or 4 + 3 (Grade Group 3), and high-risk as GS of 8 (Grade Group 4 and 5) or greater. Importantly, we defined CS disease as GS ≥ 3 + 4. I

All MRI studies were performed using 3-Tesla whole-body units (Signa HDx GE Healthcare, Waukesha, WI) using a dedicated prostate protocol in line with literature recommendations outlined by the Prostate Imaging-Reporting and Data System: 2015, Version 2.0.9 All imaging studies were reviewed by academic radiologists with training in interpreting prostate mpMRI.

Prostate biopsy
Prostate biopsies were performed as a single session of either standard transrectal ultrasound-guided 12-core systematic biopsy, or systematic biopsy and FBx (ARTEMIS ™, Eigen Inc., Grass Valley, CA) combined by obtaining ≥1 additional cores for patients with identifiable abnormal prostatic lesions per prostate mpMRI.

Statistical analysis
Statistical analysis was performed using STATA version 13.0 (StataCorp LP, College Station, TX). Mann-Whitney U Test was used to compare distribution of continuous variables. Pearson Chi square test was used to compare proportions of categorical variables. Multivariate logistic regression analysis was done to control for possible confounding clinical and demographic variables. Statistical significance was defined as a P value < 0.05.

A total of 182 (29%) Black and 437 (71%) White men were included in the analysis. Black men presenting for prostate biopsy were younger (P < 0.001) and had greater PSA (P < 0.05). Patient demographics and clinical variables are summarized in Table 1. There was a significant difference in health insurance coverage between the cohorts (Table 1).

Table 1 Clinical, demographic and pathologic data of the entire cohort.
Clinical_demographic_and_pathologic_data_of_the_entire cohort.png

A total of 266 (43%) patients underwent FBx. In the entire cohort, there was a significant difference in the use of FBx between Black and White men (41 (22.5%) vs. 225 (51.5%), P < 0.001). In the subset of biopsy naïve patients, a higher proportion of White men underwent FBx compared with Black men (108 (36.7%) vs. 19 (12.6%), P < 0.0001). However, in patients with prior negative prostate biopsy, the utilization rates of FBx were similar between the two races (71.0% Black vs. 81.8% White, P = 0.17).

Table 2 Multivariate logistic regression analysis for predictors of utilization of FBx in evaluation of prostate cancer.

A multivariate logistic regression analysis was done to evaluate if race was an independent predictor for patients getting FBx (Table 2). After adjusting for age, PSA, digital rectal exam (DRE), family history of PCa and health insurance provider, Black race was found to be a significant negative predictor of obtaining FBx (OR:0.32, 95% CI: 0.21–0.51, P < 0.001). Black patients were 68% less likely than White men to get FBx when presented with concerns of PCa.

Further multivariate regression models were created to stratify by prior biopsy history including subsets of men with a prior negative biopsy and men who were biopsy naïve (Table 3). Black race stayed an independent negative predictor (OR: 0.36, 95% CI: 0.20–0.64, P < 0.001) in the subset of patients who were biopsy naïve. However, in the cohort of patients with prior negative biopsy, while Black men were still less likely to obtain FBx, the difference between races were not statistically significant (OR: 0.51, 95% CI: 0.19–1.36, P = 0.179).

Racial disparities in PCa have been observed with respect to clinical stage at presentation, treatment modality, quality of life and mortality; however, to our knowledge this is the first investigation demonstrating that modern prostate biopsy utilization varies between White and Black men. The increased likelihood of a Black patient being diagnosed and dying of PCa10 is fundamentally problematic and challenges urologists, primary care providers and the health care system at large. While there are several factors that might account for these discrepancies, one wonders if there are any differences in how men are being evaluated for PCa detection and management. In the era of mpMRI and FBx utilization, the ability to improve the success rate in detecting CS PCa that may otherwise be underdiagnosed with systematic biopsy can alter the ultimate morbidity and mortality of these patients. Here, we retrospectively reviewed a single institutional database to evaluate any racial discrepancies in utilization of FBx for PCa evaluation and found that Black men were less likely to undergo targeted FBx when presenting with PCa suspicion.

Table 3 Multivariate logistical regression analysis stratified by prior biopsy history *controlled for age, PSA, DRE, family history and insurance provider.

In our study, Black patients presented for prostate biopsy at a younger age and with greater PSA compared with White men. This is consistent with previous studies that have found evidence that Black men present at a younger age, with more aggressive cancer and have a higher mortality from PCa compared with White men.4–7 Further evaluation of disparities within modality utilization was not performed in these studies, likely due to only recent implementation of FBx in clinical practice.

A previous multi-institutional study that found FBx to be the superior biopsy method in patients with a prior negative biopsy11 substantiates our institutional practice to obtain mpMRI for patients presenting with prior negative biopsy with the intent of pursuing FBx if a lesion is identified. This practice serves to reduce the utilization differences between the two cohorts in the setting of prior negative biopsy. This is consistent with the American Urological Association (AUA) standard operating procedure (SOP) for the use of mpMRI in patients with a prior negative biopsy [12, 13]. During the timeline of our study, there was no recommendation for the use of mpMRI in patients prior to biopsy;12 however, the AUA updated the SOP in October 2019 stating that sufficient data now exists to support the recommendation of mpMRI prior to biopsy for all men under consideration for prostate biopsy, without previous history of biopsy.13 Although mpMRI in biopsy naïve men was not recommended at the time, our findings of a racial disparity in the utilization of mpMRI-FBx in these men is significant and it will be interesting to follow if this disparity exists after implementation of these new guidelines. 

A study by Krimphove et al..14 evaluated the contribution of demographics, access to healthcare, treatment choices, and tumor characteristics to racial differences in the survival of advanced PCa. Overall, they found that accessrelated variables explained greater than 80% of the excess risk of death in Black men with PCa. Furthermore, the recent study by Dess et al. [15]. provides the most robust study to date analyzing the racial disparity in PCa mortality. After controlling for many nonbiological factors such as treatment preference and access to care, the authors found that black race did not appear to be associated with inferior stage-for-stage mortality [15]. This study provides strong support that more emphasis should be directed toward correcting the healthcare disparities faced by black men with PCa rather than race itself. Our results showing that biopsy naïve black men are less likely to receive FBx provides further evidence that the healthcare access disparities might be contributing or resulting in outcome disparities in PCa.

Communication and trust in healthcare providers can affect subsequent management and treatment of PCa.16, 17 Prior studies have concluded that there is a higher level of mistrust for healthcare services amongst the Black community,18–20 and specifically for Black men diagnosed with PCa.21 A high level of medical mistrust is associated with reported low quality of life [22] and is negatively associated with patient satisfaction and decreased desires to fully utilize health care services for Black men with PCa.23 Patient understanding of treatment options or lack thereof suggests another source of racial disparity in PCa and can implicate outcomes of therapy24 Bhuyen et al.25 study assessing providerpatient communication for PCa screening and treatment found that patient age, financial status, regular primary care provider, recent medical check-up, global health status, and marital status are significantly associated with providerpatient communication of PCa screening and treatment options. Black men are known to have significant differences in many of these factors including financial status,26, comorbid diseases such as obesity,27 marital status,28 and primary care usage.29 Collectively, these factors above can negatively affect the provider-patient communication with respect to the management of PCa and may explain the differences found in prostate biopsy selection in our study.

Given that socioeconomic factors likely played some role in the racial disparities seen in our study, it is prudent to consider the role of implicit racial bias by providers. Reports of Black male patients receiving lower quality treatments are described in a variety of diseases but have been well documented in cancer treatment [30]. Physicians generally exhibit relatively low levels of explicit bias; [31] however, non-Black healthcare providers have been shown to display substantial implicit racial bias toward Black patients at levels comparable to the general public [32]. Penner et al. [33]. conducted a study into the effects of oncologist implicit racial bias in racially discordant oncologic interactions and found that a higher level of implicit bias in oncologists (measured by The Implicit Association Test) was associated with the physician being considered less patient-centered, and compounded the difficulty in deliberating treatment options or completing the selected treatment. Considering that implicit bias may have a direct effect on the quality of care that Black men receive, it may have also affected the prostate biopsy modality provided to the Black patients in our study, which was most evident in the biopsy naïve population.

There are several limitations in our study. First, race identification was self-reported, therefore we cannot discount inherent error in patient self-identification. Second, we did not include other relevant socioeconomic variables including household income status and education-level, which may confound the FBx utilization between the two cohorts of interest. Third, we did not control for patient preferences for biopsy as it is reasonable to suspect some patients chose not to undergo mpMRI-FBx and elected to pursue systematic biopsy voluntarily. Fourth, inherent limitations are present as this is a retrospective review of a single institution database; a multi-institutional study would better elicit racial differences in FBx utilization as there may be inherent differences in study populations and standard of care practices in different institutions.

In conclusion, this study represents the first examination of how a disparity in PCa biopsy methods may account for racial variation in detection of CS PCa. Our results provide quantitative information that race was a significant predictor of FBx use after adjusting for other confounders. In an anticipation of movement toward FBx as a standard for the PCa diagnosis, the discrepancy in utilization may become an origin of divergence in the management and outcome between the two largest populations of men at risk for PCa.

Compliance with ethical standards Conflict of interest The authors declare that they have no conflict of interest. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Authors: Connor Hoge1, Sadhna Verma2,  Daniel J. Lama1,  Ilana Bergelson1,  Monzer Haj-Hamed1, Sean Maynor1, Krishnanath Gaitonde1, Abhinav Sidana1
1. Division of Urology, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
2. Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA

Received: 11 February 2020 / Accepted: 26 February 2020 / Published online: 9 March 2020 © The Author(s), under exclusive licence to Springer Nature Limited 2020
Prostate Cancer and Prostatic Diseases (2020) 23:567–572 https://doi.org/10.1038/s41391-020-0223-5


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