Prostate Cancer: Comprehensive Review with Advanced mpMRI Insights

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 Prostate Cancer: Comprehensive Review with Advanced mpMRI Insights

doi:10.1148/radiol.250413

Introduction

Prostate cancer is the second most common cancer in men worldwide and a leading cause of cancer-related mortality. 

Its detection and management have evolved significantly over the past two decades, with multiparametric MRI (mpMRI) emerging as a key diagnostic tool.

The latest research demonstrates that integrating apparent diffusion coefficient (ADC) values and prostate-specific antigen density (PSAD) into mpMRI interpretation substantially improves the positive predictive value (PPV) for clinically significant prostate cancer (csPCa) across PI-RADS categories. 

This article reviews the cause, etiology, pathophysiology, epidemiology, clinical presentation, imaging features, treatment, and prognosis of prostate cancer, while incorporating these novel imaging insights.

1. Cause and Etiology

Prostate cancer arises from the malignant transformation of the epithelial cells lining the prostate gland. Its etiology is multifactorial, with key risk factors including:

  1. Genetic predisposition – BRCA1/2 mutations, HOXB13 gene mutation, and family history.

  2. Ethnicity – Higher incidence in African-American men; lower in Asian men.

  3. Hormonal influences – Androgen levels play a central role in tumor growth.

  4. Environmental and lifestyle factors – High-fat diets, obesity, and sedentary lifestyle.

  5. Chronic inflammation – Proliferative inflammatory atrophy may progress to prostatic intraepithelial neoplasia (PIN) and adenocarcinoma.

2. Pathophysiology

Prostate cancer typically originates in the peripheral zone (≈70% of cases), with gradual progression from:

  • Prostatic intraepithelial neoplasia (PIN) → Localized adenocarcinoma → Locally advanced disease → Metastasis.

Key pathological processes include:

  • Androgen receptor signaling drives tumor proliferation.

  • Loss of tumor suppressor genes (PTEN, TP53) and oncogene activation (MYC).

  • Angiogenesis supporting tumor growth and spread.

  • Perineural invasion, a common feature facilitating local spread to surrounding tissues.

3. Epidemiology

  • Incidence: Second most diagnosed cancer in men worldwide; highest rates in North America, Europe, and Australia.

  • Age: Rare before 50; median diagnosis age is ≈66 years.

  • Mortality: The Fifth leading cause of cancer death in men globally.

  • Trends: Widespread PSA screening initially increased detection rates, followed by stabilization as guidelines evolved.

4. Clinical Presentation

Many cases are asymptomatic in the early stages. When symptomatic, common presentations include:

  • Lower urinary tract symptoms (frequency, urgency, nocturia, weak stream).

  • Hematuria or hematospermia.

  • Erectile dysfunction.

  • Bone pain in metastatic disease (especially to spine, pelvis, ribs).

5. Imaging Features

5.1 Role of mpMRI

Multiparametric MRI combines T2-weighted imaging, diffusion-weighted imaging (DWI), ADC maps, and dynamic contrast-enhanced (DCE) sequences to evaluate prostate lesions.
PI-RADS v2.1 scoring system standardizes acquisition and interpretation.

Key limitation: mpMRI alone can yield false positives—PPV ≈35% for PI-RADS ≥3 lesions.

5.2 Enhancing Diagnostic Accuracy with ADC and PSAD

Recent evidence suggests:

  • Low ADC values (≤0.9 × 10⁻³ mm²/sec) are associated with a higher likelihood of csPCa.

  • High PSAD (≥0.15 ng/mL²) independently predicts malignancy.

When combined:

  • PPV increased from 12% (high ADC + low PSAD) to 60% (low ADC + high PSAD).

  • Improvements were consistent across PI-RADS 3, 4, and 5 categories.

[Table] Summary of PPV improvements for csPCa with combined ADC and PSAD analysis.

PI-RADS   ADC >0.9 + PSAD <0.15   ADC ≤0.9 + PSAD ≥0.15
3    5%   32%
4    14%   59%
5    24%   73%

[Figure] Impact of dichotomized ADC and PSAD on PPV across PI-RADS categories – PPV significantly increases in the low ADC/high PSAD group compared to high ADC/low PSAD.


5.3 Interpretation in Clinical Context

Incorporating ADC and PSAD into mpMRI reporting:

  • Helps target biopsies to high-risk lesions.

  • May reduce unnecessary biopsies in low-probability cases.

  • Requires further research on potential effects on sensitivity and negative predictive value.

6. Treatment

Treatment is individualized based on risk stratification (PSA, Gleason grade group, clinical stage).

Options include:

  1. Active surveillance – For low-risk disease.

  2. Radical prostatectomy – Open, laparoscopic, or robotic-assisted.

  3. Radiation therapy – External beam or brachytherapy.

  4. Androgen deprivation therapy (ADT) – For advanced or recurrent disease.

  5. Novel systemic agents – Abiraterone, enzalutamide, PARP inhibitors.

  6. Chemotherapy – Docetaxel in metastatic castration-resistant cases.

7. Prognosis

  • Localized disease: 5-year relative survival >98%.

  • Metastatic disease: 5-year survival ≈30%.

  • Prognosis strongly depends on Gleason grade, stage, and treatment response.

  • Incorporation of advanced imaging biomarkers (ADC, PSAD) may improve early detection of clinically significant disease, potentially improving long-term outcomes.

8. Conclusion

Prostate cancer remains a major public health concern.
The integration of lesion-level ADC values and PSAD thresholds into mpMRI interpretation significantly improves PPV across PI-RADS categories, aiding in the more accurate detection of csPCa.
These findings suggest a future where personalized imaging interpretation could refine biopsy decisions and optimize patient management.

Quiz

Question 1: Which combination of ADC and PSAD values yields the highest PPV for clinically significant prostate cancer?
a) ADC >0.9 × 10⁻³ mm²/sec, PSAD <0.15 ng/mL²
b) ADC ≤0.9 × 10⁻³ mm²/sec, PSAD ≥0.15 ng/mL²
c) ADC >0.9 × 10⁻³ mm²/sec, PSAD ≥0.15 ng/mL²
d) ADC ≤0.9 × 10⁻³ mm²/sec, PSAD <0.15 ng/mL²

Question 2: Which PI-RADS category shows the greatest relative PPV increase when combining ADC and PSAD?
a) 3
b) 4
c) 5
d) All show equal increase

Answer & Explanation

1. Answer: b). Explanation: Low ADC and high PSAD are both independent predictors of higher PPV for csPCa; combining them gives the highest PPV.

2. Answer: a). Explanation: While absolute PPV is higher in PI-RADS 5, the relative jump (from 5% to 32%) is most dramatic in PI-RADS 3 lesions.

References

[1] S. J. C. Soerensen et al., “Impact of ADC values and PSAD thresholds on mpMRI PPV in prostate cancer detection,” Radiology, vol. 308, no. 2, pp. 455–466, 2023.
[2] F. H. Verburg et al., “Role of mpMRI in prostate cancer detection,” Eur Urol, vol. 79, no. 3, pp. 327–336, 2021.
[3] J. Turkbey et al., “PI-RADS v2.1: A critical update,” J Magn Reson Imaging, vol. 51, no. 3, pp. 660–669, 2020.
[4] A. Ahmed et al., “Diagnostic accuracy of mpMRI and TRUS biopsy in prostate cancer,” Lancet, vol. 389, no. 10071, pp. 815–822, 2017.
[5] D. Barentsz et al., “Prostate MRI and biopsy: state of the art,” Eur Urol, vol. 71, no. 4, pp. 630–632, 2017.
[6] R. C. Thompson et al., “PSA density as a predictor of prostate cancer,” Urology, vol. 105, pp. 102–107, 2017.
[7] A. Shukla-Dave et al., “ADC values in prostate cancer: correlation with Gleason score,” Radiology, vol. 259, no. 2, pp. 412–420, 2011.

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