on June 16, 2026
Prostate cancer is one of the most frequently diagnosed malignancies in adult men. In recent decades, improvements in diagnostic techniques have increased the number of diagnoses, sparking an important debate over the benefits of early diagnosis versus the risk of overdiagnosis and overtreatment.
Today, the diagnostic pathway for prostate cancer (PCa) is no longer based exclusively on PSA testing, but on an integrated assessment that includes genetic factors, advanced biomarkers, next-generation imaging, and individual risk stratification.
Population screening and opportunistic screening: two different concepts
Population screening involves systematically performing tests on asymptomatic men in groups considered at risk, with the aim of detecting disease at an early stage.
Early diagnosis or opportunistic screening is a different concept, arising from an individual assessment carried out by the primary care physician based on age, family history, symptoms, comorbidities, and personal risk factors.
The modern goal is not to identify as many cancers as possible, but to recognize those that are clinically significant, reducing unnecessary invasive procedures.
Family history and genetics: how much does hereditary risk matter?
A family history increases the risk of developing prostate cancer, suggesting a significant genetic component.
However, only a relatively limited proportion of cases, estimated to be around 9%, meet the definition of hereditary prostate cancer, generally identified by the presence of at least two family members with early-onset disease.
Modern genomic analyses have identified over 100 susceptibility loci, capable of explaining approximately 39% of familial risk.
Among the most studied genes are:
BRCA1
BRCA2
HOXB13
Germline mutations in these genes can increase the risk of developing the disease and, in some contexts, make targeted genetic counseling useful.
Digital rectal examination: a tool that is still relevant
Despite technological advances, digital rectal examination still plays an important clinical role.
Most prostate cancers originate in the peripheral zone of the gland and can become palpable when they reach a volume of approximately 0.2 cm³.
Although it has sensitivity limitations, the clinical examination remains simple, quick, and complementary to other diagnostic tools.
PSA: beyond the absolute value
PSA (Prostate Specific Antigen) is the most widely used biomarker in clinical practice, but its absolute value should not be interpreted in isolation.
PSA density
PSA density is calculated by dividing the serum PSA value by the prostate volume measured by imaging.
Higher values increase the probability that the cancer is clinically significant.
PSA velocity (PSAV)
It expresses the annual variation of PSA in ng/mL per year.
PSA doubling time (PSA-DT)
It measures the rate at which PSA increases over time according to an exponential trend.
These parameters help determine whether a variation is consistent with benign phenomena or a possible neoplastic progression.
It is important to remember that an isolated increase in PSA does not automatically indicate a need for a biopsy.
The test should be repeated after a few weeks in the same laboratory and using a standardized method. The empirical use of antibiotics in asymptomatic subjects solely to reduce PSA is not recommended.
Next-generation biomarkers: toward a more selective diagnosis
The evolution of biomarkers is seeking to improve the distinction between aggressive cancers and indolent forms.
Free/total PSA ratio
It can contribute to the clinical assessment, but must be interpreted with caution as it is influenced by conditions such as benign prostatic hyperplasia and glandular volume.
PHI – Prostate Health Index
It combines three parameters:
Total PSA
Free PSA
[-2]proPSA (p2PSA)
Its main goal is to reduce unnecessary biopsies.
4Kscore test
It integrates:
Total PSA
Free PSA
Intact PSA
hK2 (human kallikrein-2)
It allows for a more refined estimate of the risk of clinically significant cancer.
Urinary PCA3
It is a biomarker derived from non-coding RNA detectable in urine collected after prostatic massage.
Urinary biomarkers HOXC6 and DLX1
Measuring the expression of these mRNAs allows for an estimate of the risk of biopsy positivity and high-risk disease.
Prostate biopsy and new imaging techniques
Ultrasound-guided prostate biopsy still represents the diagnostic gold standard today.
It can be performed using a:
transrectal
transperineal
Conventional transrectal ultrasound has limitations in its diagnostic capacity; new methods such as elastography and contrast-enhanced ultrasound are under study.
Multiparametric MRI and PSMA-PET: the future is already here
Multiparametric magnetic resonance imaging (mpMRI) has profoundly changed the diagnostic pathway.
Thanks to its high sensitivity in localizing lesions, it is increasingly used before biopsy.
A further technological leap is represented by PET with PSMA (Prostate-Specific Membrane Antigen).
The main indications recognized by the guidelines include:
restaging after radical prostatectomy with PSA above 0.2 ng/mL when the result changes therapeutic decisions
restaging after radical radiotherapy with an increase above 2 ng/mL compared to the nadir (Phoenix criterion)
assessment in patients with castration-resistant carcinoma and negative conventional imaging
there is also growing evidence for its use in the preoperative staging of high-risk patients.
Diet and lifestyle: how much do they affect risk?
Diet is not a single cause of prostate cancer, but some dietary patterns have been associated with changes in risk.
High alcohol consumption has been associated with an increase in both diagnosis and specific mortality.
High consumption of milk proteins shows a weak but possible correlation with the risk of disease.
Fried foods may be associated with an increased risk.
For long-chain omega-3 fatty acids, there is no compelling evidence of increased risk.
Lycopene has shown a favorable association in reducing incidence.
Phytoestrogens have also been associated with a reduction in risk in several epidemiological analyses.
Regarding vitamin D and selenium, the available results remain conflicting and do not currently support systematic supplementation for preventive purposes.
Conclusions
The early diagnosis of prostate cancer is evolving toward a personalized approach that integrates family history, genomics, advanced biomarkers, and precision imaging.
The goal is not to indiscriminately increase the number of diagnoses, but to identify the cancers that truly require treatment, reducing invasive procedures and improving the benefit-risk ratio for the patient.
The decision to perform further tests must always arise from a shared assessment between the doctor and the patient, considering age, life expectancy, general health conditions, and individual preferences.
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