Genetic and biological drivers of prostate cancer disparities in Black men

Gong, Jun; Kim, Daniel M.; Freeman, Michael R.; Kim, Hyung; Ellis, Leigh; Smith, Bethany; Theodorescu, Dan; Posadas, Edwin; Figlin, Robert; Bhowmick, Neil; Freedland, Stephen J.

doi:10.1038/s41585-023-00828-w

Cited by 10 publications

(4 citation statements)

References 219 publications

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“…It has become generally accepted that the underlying causes of health inequities are multi-factorial and include biological, structural, and social determinants [29]. In this context healthcare, genetic and biological differences appear to be impactful drivers of disparity in prostate cancer [30,31]. Of note, the lack of inclusive genetic tests and genetic testing is an important challenge in health care.…”

Section: Healthcare Inequalities In Prostate Cancermentioning

confidence: 99%

Germline Mutations and Ancestry in Prostate Cancer

Bataba,

Babcock,

Isensee

et al. 2024

Curr Oncol Rep

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Purpose of Review Prostate cancer is the most frequently diagnosed non-cutaneous malignancy of men in the USA; notably, the incidence is higher among men of African, followed by European and Asian ancestry. Germline mutations and, in particular, mutations in DNA damage repair genes (DDRGs) have been implicated in the pathogenesis of prostate cancer. This review intends to discuss the implication of ancestry on prostate cancer, specifically in regard to lack of diversity in genomic and genetic databases and the ability of providers to properly counsel patients on the significance of cancer genetic results. Recent Findings Ancestral differences in prostate cancer-associated DDRG germline mutations are increasingly recognized. Guidelines for treatment by the National Comprehensive Cancer Network® (NCCN®) support germline testing in certain patients, and a myriad of genetic testing panels for DDRG mutations are now available in clinical practice. However, the consensus among providers on what genes and mutations to include in the genetic tests has evolved from experience from men of European ancestry (EA). Gaps in ancestry-informed clinical practice exist in genetic risk assessment, implementation of screening, counseling, guiding recommendations, treatment, and clinical trial enrollment. Summary The lack of diversity in tumor genomic and genetic databases may hinder ancestry-specific disease-predisposing alterations from being discovered and targeted in prostate cancer and, therefore, impede the ability of providers to accurately counsel patients on the significance of cancer genetic test results.

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Section: Healthcare Inequalities In Prostate Cancermentioning

confidence: 99%

Germline Mutations and Ancestry in Prostate Cancer

Bataba,

Babcock,

Isensee

et al. 2024

Curr Oncol Rep

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“…In South Africa, 1 in 28 men are affected, with more than 20% of diagnosed patients dying from the disease. African men are six times more likely to develop prostate cancer compared to those in most developed countries, and the disease tends to follow a more aggressive course [ 2 ] due to multiple factors such as genetic alterations, protein differences, tumour microenvironment, and even circulating hormones and vitamins that might contribute to the differing phenotypes [ 3 , 4 , 5 ]. These differences in tumour biology result in more rapid prostate tumour growth and earlier transformation from indolent to aggressive disease [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…These differences in tumour biology result in more rapid prostate tumour growth and earlier transformation from indolent to aggressive disease [ 2 ]. In addition, cultural factors and poverty result in delays in accessing healthcare services; as a result, the patients present at more advanced disease stages, which may render them unsuitable for localised therapies [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

A Comparison of 68Ga-PSMA PET/CT-Based Split Renal Function with 99mTc-MAG3 Renography in Patients with Metastatic Castration-Resistant Prostate Carcinoma Treated with 177Lu-PSMA

Gabela,

Mkhize,

Hadebe

et al. 2024

Diagnostics

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Background: Physiological PSMA expression in the cells of the proximal renal tubules and consecutive radiopharmaceutical binding and retention could potentially lead to radioligand-therapy-induced nephrotoxicity. Thus, patients with metastatic castration-resistant prostate cancer undergo 99mTc-Mercaptoacetyltriglycine (MAG3) renal scintigraphy to assess kidney function and to exclude renal obstruction as part of their workup for PSMA-targeted radioligand therapy (RLT). 99mTc-MAG-3 renal scintigraphy often requires an additional visit to the nuclear medicine department and patients spend 30–90 min in the department, which is inconvenient and takes up camera time. In addition, the patients are subjected to a baseline 68Ga-PSMA PET/CT to assess for PSMA-positive disease prior to targeted radioligand therapy. The aim of this retrospective cross-sectional study was to compare 99mTc-MAG-3-based split renal function (SRF) with 68Ga-PSMA-derived SRF. Methods: This retrospective cross-sectional study included 28 patients with histologically proven metastatic castration-resistant prostate cancer (mCRPC) who received 177Lu-PSMA617. A comparison between the split renal function using 68Ga-PSMA PET/CT and the 99mTc-MAG-3-derived split renal function was carried out in 56 kidneys (n = 56). The SRF on 68Ga-PSMA was calculated using the volume and the average standard uptake value (SUVmean) within each VOI calculated as previously described by Roser et al.: SRF = (VOLUMEright) ∗ SUVmeanright/(VOLUMEright ∗ SUVmeanright + VOLUMEleft ∗ SUVmeanleft). Paired tests and correlation coefficients were used to compare 68Ga-PSMA and 99mTc-MAG-3. A visual comparison of kidney morphology on both studies was also performed. Results: The median SRF of the right kidney was 49.9% (range: 3–91%) using 68Ga-PSMA PET/CT and 50.5% (range: 0–94%) with 99mTc-MAG3 scintigraphy. Notably, there was a strong correlation between SRF measurements obtained from PSMA and 99mTcMAG3, with a Pearson correlation coefficient of 0.957 (p < 0.001). Both 99mTc-MAG3 and 68Ga-PSMA PET/CT studies identified morphological renal abnormalities; there were nine hydronephrotic kidneys, four shrunken kidneys and one obstructed kidney, and there was a strong positive correlation between 68Ga-PSMA kidney morphology and 99mTcMAG3 renal scintigraphy kidney morphology, with a correlation coefficient of 0.93. Conclusions: PSMA-derived split function demonstrated a high correlation with renal function assessed on diuretic 99mTc-MAG3 renograms. PET-derived split renal function may, therefore, be considered an alternative to diuretic renogram-based split function. Furthermore, both 99mTc-MAG3 and 68Ga-PSMA PET/CT studies identified morphological renal abnormalities such as hydronephrosis, shrunken and obstructed kidneys. This correlation underscores the potential utility of 68Ga-PSMA imaging as a valuable tool for assessing kidney morphology as an alternative to renogram split function in clinical practice.

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“…Prostate cancer has the greatest US racial disparity of any cancer, with self-reported Black men having twice the mortality rate compared with US men of other races . Although structural and social determinants of health are key contributors and ensuring equal access to quality care is critical, significant differences in prostate cancer biology exist by self-reported race . Acknowledging race as a social construct and a poor proxy for ancestry, these differences are unlikely to be solely genetic, but rather could be a physiological response to psychosocial stressors and systemic inequities .…”

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confidence: 99%

A Pragmatic Approach to Prostate Cancer Screening

Tosoian,

Penson,

Chinnaiyan

2024

JAMA

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The introduction of prostate-specific antigen (PSA)-based screening for prostate cancer in the early 1990s was followed by a nearly 2-decade long decline in prostate cancer metastasis and mortality. 1 However, clinical trial data revealed that screening was associated with substantial harms. 2 Under the traditional clinical approach in which elevated serum PSA triggered prostate biopsy, roughly 1 in 5 screened men underwent biopsies, with more than 75% found to be negative and a majority of positive biopsies harboring low-grade, clinically insignificant cancers. 3 Prostate biopsies are uncomfortable for patients and carry a risk of bleeding and infection requiring hospitalization. 4 Moreover, during a previous era in which a cancer diagnosis was inexorably linked to treatment, overdiagnosis (ie, detection of indolent cancers that would not have been detected during life in the absence of screening) and overtreatment resulted in significantly reduced quality of life. 5 In 2012, the US Preventive Services Task Force (USPSTF) provided a grade D recommendation against the use of PSA screening, concluding that the benefits of PSA-based screening for prostate cancer do not outweigh the harms. 6 In the time since, longer-term outcomes from highquality studies have better informed the benefits of screening. After 22 years of follow-up in the Gotebörg screening trial, 7 the rate ratio for prostate cancer death in screening participants was 0.59 (95% CI, 0.43-0.80), with a number needed to invite to screening of 221 and number needed to treat of 9 to prevent 1 death from prostate cancer-figures that compare favorably with other common cancers. 8,9 At the same time, a growing understanding of prostate cancer has led to advances to reduce the harms previously associated with screening. For men with favorable-risk cancers, adoption of active surveillance-a management strategy centered on monitoring rather than immediate treatment-has reduced overtreatment and its associated adverse effects. 10 In large part due to these studies quantifying benefit and development of approaches to minimize harms, in 2018 the USPSTF offered an updated grade C recommendation for PSA screening, recommending individualized decision-making in men aged 55-69 years. 11 Current clinical guidelines emphasize a narrowed diagnostic focus on identifying higher-grade cancers, recommending that patients with an elevated PSA level undergo magnetic resonance imaging (MRI), if available, or biomarker testing to better define the risk of high-grade (grade group [GG] ≥2) disease prior to biopsy. 12-14 Indeed, MRI with targeted biopsy improves detection of high-grade cancers relative to stan-Multimedia

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Genetic and biological drivers of prostate cancer disparities in Black men

Cited by 10 publications

References 219 publications

Germline Mutations and Ancestry in Prostate Cancer

Germline Mutations and Ancestry in Prostate Cancer

A Comparison of 68Ga-PSMA PET/CT-Based Split Renal Function with 99mTc-MAG3 Renography in Patients with Metastatic Castration-Resistant Prostate Carcinoma Treated with 177Lu-PSMA

A Pragmatic Approach to Prostate Cancer Screening

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