Diagnosis
The diagnosis and staging of prostate cancer are based on the integrated assessment of clinical findings, laboratory parameters, imaging, and histopathological examination.
PSA Level
An elevated serum PSA level is a common initial finding prompting further evaluation. Prostate-specific antigen is a serine protease produced by prostatic epithelial cells. Elevated PSA concentrations may occur in prostate cancer but are not cancer-specific and may also be seen in benign prostatic hyperplasia, prostatitis, urinary retention, or following manipulation of the prostate. Interpretation therefore includes not only the absolute PSA concentration but also PSA kinetics, clinical context, prostate volume, and, where appropriate, PSA density.
Digital Rectal Examination
Digital rectal examination (DRE) is generally performed as part of the clinical assessment. The posterior surface of the prostate is palpated through the rectum to identify induration, nodularity, asymmetry, or other findings suspicious for malignancy. MRI When clinically significant prostate cancer remains suspected, multiparametric magnetic resonance imaging (mpMRI) of the prostate is now a central component of the diagnostic pathway. mpMRI provides high-resolution anatomical and functional assessment of suspicious intraprostatic lesions and supports targeted biopsy planning.
PI-RADS (Prostate Imaging Reporting and Data System)
PI-RADS is a standardized reporting and assessment system for prostate mpMRI. It provides a structured estimate of the likelihood that an imaging abnormality represents clinically significant prostate cancer.
- PI-RADS 1: very low likelihood of clinically significant prostate cancer
- PI-RADS 2: low likelihood; findings are probably benign
- PI-RADS 3: intermediate/equivocal likelihood
- PI-RADS 4: high likelihood of clinically significant prostate cancer
- PI-RADS 5: very high likelihood of clinically significant prostate cancer
Prostate Biopsy
Definitive diagnosis requires histopathological confirmation by prostate biopsy. Multiple tissue cores are obtained, increasingly via a transperineal approach, with MRI-targeted sampling of suspicious lesions frequently combined with systematic biopsy. Microscopic demonstration of malignant prostatic epithelial cells establishes the diagnosis.
Gleason Score
Histopathological assessment provides essential information regarding tumor differentiation and biological aggressiveness. The Gleason grading system and the corresponding ISUP Grade Groups are central to risk stratification. The Gleason score reflects the architectural differentiation of prostate adenocarcinoma compared with normal prostatic glandular tissue. The pathologist identifies the predominant and second most prevalent growth patterns. These are reported separately, with the predominant pattern first.
3 + 4 = 7 or 4 + 3 = 7
Although both combinations yield a total Gleason score of 7, their biological behavior differs:
- 3 + 4 = 7: Gleason pattern 3 predominates, with a smaller component of pattern 4; corresponds to ISUP Grade Group 2
- 4 + 3 = 7: Gleason pattern 4 predominates and is associated with a less favorable biological profile; corresponds to ISUP Grade Group 3
Gleason patterns historically range from 1 to 5; in contemporary diagnostic practice, prostate carcinoma is predominantly assigned patterns 3, 4, and 5.
- Gleason pattern 3: relatively well-formed, discrete glandular structures; generally associated with less aggressive behavior
- Gleason pattern 4: poorly formed, fused, cribriform, or glomeruloid glandular architecture; associated with greater biological aggressiveness
- Gleason pattern 5: essentially absent glandular differentiation, including solid sheets, cords, single cells, or comedonecrosis; represents highly aggressive tumor architecture
Gleason score 6 (3 + 3) is the lowest score routinely assigned to prostate adenocarcinoma in current practice and corresponds to ISUP Grade Group 1. Gleason score 7 represents intermediate-grade disease, with the distinction between 3 + 4 and 4 + 3 being clinically important. Gleason scores 8–10 correspond to high-grade disease with an increased risk of local progression, metastatic dissemination, and prostate-cancer-specific mortality.
Tumor extent is additionally classified according to the TNM system:
- T: local extent of the primary tumor within or beyond the prostate
- N: regional lymph-node involvement
- M: presence of distant metastatic disease
Additional staging investigations may include:
- PSMA PET/CT
- Computed tomography (CT)
- Magnetic resonance imaging (MRI)
Bone scintigraphy, particularly when osseous metastatic disease is suspected Treatment decisions integrate multiple prognostic and patient-related factors:
- PSA level
- Gleason score / ISUP Grade Group
- Clinical and/or pathological tumor stage
- Patient age and performance status
- Comorbidities
- Individual patient preferences