Association between prostate size and the incidence of prostate cancer: a meta-analysis and review for urologists and clinicians

Moolupuri, Abhilash; Camacho, Jaime; Riese, Werner de

doi:10.1007/s11255-021-02892-w

Cited by 14 publications

(8 citation statements)

References 11 publications

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“…There is also previous evidence that gland volume may have an inverse correlation with prostate cancer incidence though these studies were done in the pre-MRI era. 35,36 Interestingly, in this study using MRI-based diagnostics, we were able to recapitulate this observation with benign cases having overall larger volumes compared to glands with cancer detected. The mechanisms of this are unclear though some have proposed that it may be due to a mass compressive effect.…”

Section: Discussionsupporting

confidence: 63%

Re-evaluating the diagnostic efficacy of PSA as a referral test to detect clinically significant prostate cancer in contemporary MRI-based image-guided biopsy pathways

Lophatananon

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Burns-Cox

et al. 2021

Journal of Clinical Urology

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Introduction: Modern image-guided biopsy pathways at diagnostic centres have greatly refined the investigations of men referred with suspected prostate cancer. However, the referral criteria from primary care are still based on historical prostate-specific antigen (PSA) cut-offs and age-referenced thresholds. Here, we tested whether better contemporary pathways and biopsy methods had improved the predictive utility value of PSA referral thresholds. Methods: PSA referral thresholds, age-referenced ranges and PSA density (PSAd) were assessed for positive predictive value (PPV) in detection of clinically significant prostate cancer (csPCa – histological ⩾ Grade Group 2). Data were analysed from men referred to three diagnostics centres who used multi-parametric magnetic resonance imaging (mpMRI)-guided prostate biopsies for disease characterisation. Findings were validated in a separate multicentre cohort. Results: Data from 2767 men were included in this study. The median age, PSA and PSAd were 66.4 years, 7.3 ng/mL and 0.1 ng/mL2, respectively. Biopsy detected csPCa was found in 38.7%. The overall area under the curve (AUC) for PSA was 0.68 which is similar to historical performance. A PSA threshold of ⩾ 3 ng/mL had a PPV of 40.3%, but this was age dependent (PPV: 24.8%, 32.7% and 56.8% in men 50–59 years, 60–69 years and ⩾ 70 years, respectively). Different PSA cut-offs and age-reference ranges failed to demonstrate better performance. PSAd demonstrated improved AUC (0.78 vs 0.68, p < 0.0001) and improved PPV compared to PSA. A PSAd of ⩾ 0.10 had a PPV of 48.2% and similar negative predictive value (NPV) to PSA ⩾ 3 ng/mL and out-performed PSA age-reference ranges. This improved performance was recapitulated in a separate multi-centre cohort ( n = 541). Conclusion: The introduction of MRI-based image-guided biopsy pathways does not appear to have altered PSA diagnostic test characteristics to positively detect csPCa. We find no added value to PSA age-referenced ranges, while PSAd offers better PPV and the potential for a single clinically useful threshold (⩾0.10) for all age groups. Level of evidence: IV

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Section: Discussionsupporting

confidence: 63%

Re-evaluating the diagnostic efficacy of PSA as a referral test to detect clinically significant prostate cancer in contemporary MRI-based image-guided biopsy pathways

Lophatananon

Light

Burns-Cox

et al. 2021

Journal of Clinical Urology

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“…Since then, other studies have reported identical findings. In a meta-analysis compiled by Moolupuri et al, 28 out of 30 studies showed a clear inverse relationship between prostate size and the chance of finding prostate cancer at biopsy [ 16 ]. The remaining 2 studies were equivocal and none showed a positive correlation.…”

Section: Introductionmentioning

confidence: 99%

Urinary symptoms and prostate cancer—the misconception that may be preventing earlier presentation and better survival outcomes

Gnanapragasam

Greenberg

Burnet

2022

BMC Med

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Background Prostate cancer is an epidemic of the modern age, and despite efforts to improve awareness, it remains the case that mortality has hardly altered over the decades, driven largely by late presentation. There is a strong public perception that male urinary symptoms is one of the key indicators of prostate cancer, and this continues to be part of messaging from national guidelines and media health campaigns. This narrative, however, is not based on evidence and may be seriously hampering efforts to encourage early presentation. Discussion Anatomically, prostate cancer most often arises in the peripheral zone, while urinary symptoms result from compression of the urethra by prostatic enlargement more centrally. Biopsy studies show that mean prostate volume is actually lower in men found to have (early) prostate cancer compared to those with benign biopsies. This inverse relationship between prostate size and the probability of cancer is so strong that PSA density (PSA corrected for prostate volume) is known to be significantly more accurate in predicting a positive biopsy than PSA alone. Thus, this disconnect between scientific evidence and the current perception is very striking. There is also evidence that using symptoms for investigating possible cancer may lead to higher proportions of men presenting with locally advanced or metastatic disease compared to PSA testing or screening programmes. Concerns about overwhelming health care services if men are encouraged to get tested without symptoms may also be overstated, with recent newer approaches to reduce over-investigation and treatment. In this article, we explore the link between urinary symptoms and prostate cancer and propose that public and professional messaging needs to change. Conclusion If rates of earlier diagnosis are to improve, we call for strong clear messaging that prostate cancer is a silent disease especially in the curable stages and men should come forward for testing regardless of whether or not they have symptoms. This should be done in parallel with other ongoing efforts to raise awareness including targeting men at highest risk due to racial ancestry or family history. While the current resurgence in interest and debate about prostate cancer screening is timely, change of this message by guideline bodies, charities and the media can be a first simple step to improving earlier presentation and hence cures rates.

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“…Prostate cancer (PCa) is considered the second most widespread carcinoma and the fifth reason for cancer-related death among men around the world [1,2]. Over onehalf of males 50 years or older show either histological and/or clinical signs of benign prostatic hypertrophy (BPH) [3]. PCa identification rates show great variation worldwide, with a higher incidence in the USA and Europe than in South and East Asia [4].…”

Section: Introductionmentioning

confidence: 99%

“…About 20% of 191,000 PCa cases identified in 2020 in the USA alone were found to be metastatic [4,6]. Uncontrolled proliferation of oncogenic cells in the prostatic tissue under the influence of testosterone and 5α-dihydrotestosterone (DHT) on androgenic receptors is the main characteristic of both PCa and BPH [3,7]. The main challenge in cancer treatment is the high toxicity profiles of most anticancer drugs [8].…”

Section: Introductionmentioning

confidence: 99%

Cholesterol-Based Nanovesicles Enhance the In Vitro Cytotoxicity, Ex Vivo Intestinal Absorption, and In Vivo Bioavailability of Flutamide

et al. 2021

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Critical adverse effects and frequent administration, three times per day, limit the use of flutamide (FLT) as a chemotherapeutic agent in the treatment of prostate cancer. Therefore, our research aimed to develop new cholesterol-based nanovesicles for delivering FLT to malignant cells in an endeavor to maximize its therapeutic efficacy and minimize undesired adverse effects. Draper–Lin small composite design was used to optimize the critical quality attributes of FLT-loaded niosomes and ensure the desired product quality. The influence of the selected four independent variables on mean particle size (Y1), zeta potential (Y2), drug entrapment efficiency (Y3), and the cumulative drug release after 24 h (Y4) was examined. The optimized nanovesicles were assessed for their in vitro cytotoxicity, ex-vivo absorption via freshly excised rabbit intestine as well as in vivo pharmacokinetics on male rats. TEM confirmed nanovescicles’ spherical shape with bilayer structure. Values of dependent variables were 748.6 nm, −48.60 mV, 72.8% and 72.2% for Y1, Y2, Y3 and Y4, respectively. The optimized FLT-loaded niosomes exerted high cytotoxic efficacy against human prostate cancer cell line (PC-3) with an IC50 value of 0.64 ± 0.04 µg/mL whilst, it was 1.88 ± 0.16 µg/mL for free FLT. Moreover, the IC50 values on breast cancer cell line (MCF-7) were 0.27 ± 0.07 µg/mL and 4.07 ± 0.74 µg/mL for FLT-loaded niosomes and free FLT, respectively. The permeation of the optimized FLT-loaded niosomes through the rabbit intestine showed an enhancement ratio of about 1.5 times that of the free FLT suspension. In vivo pharmacokinetic study displayed an improvement in oral bioavailability of the optimized niosomal formulation with AUC and Cmax values of 741.583 ± 33.557 μg/mL × min and 6.950 ± 0.45 μg/mL compared to 364.536 ± 45.215 μg/mL × min and 2.650 ± 0.55 μg/mL for the oral FLT suspension. With these promising findings, we conclude that encapsulation of FLT in cholesterol-loaded nanovesicles enhanced its anticancer activity and oral bioavailability which endorse its use in the management of prostate cancer.

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Association between prostate size and the incidence of prostate cancer: a meta-analysis and review for urologists and clinicians

Cited by 14 publications

References 11 publications

Re-evaluating the diagnostic efficacy of PSA as a referral test to detect clinically significant prostate cancer in contemporary MRI-based image-guided biopsy pathways

Re-evaluating the diagnostic efficacy of PSA as a referral test to detect clinically significant prostate cancer in contemporary MRI-based image-guided biopsy pathways

Urinary symptoms and prostate cancer—the misconception that may be preventing earlier presentation and better survival outcomes

Cholesterol-Based Nanovesicles Enhance the In Vitro Cytotoxicity, Ex Vivo Intestinal Absorption, and In Vivo Bioavailability of Flutamide

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