Prostate Cancer and PSA Interpretation
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Direct answer
Prostate cancer is an adenocarcinoma of the prostatic glands, most often arising in the peripheral zone, and it is usually suspected through serum PSA and digital rectal examination. PSA is an organ-specific but not cancer-specific protease, so a raised value must be confirmed by biopsy. Gleason grading and staging then guide treatment, and androgen deprivation therapy remains the main systemic treatment for advanced disease.
What you must remember
- Site of origin: the peripheral zone is most often involved, so cancer is palpable on digital rectal examination as a firm, asymmetric nodule.
- PSA: a kallikrein-related serine protease secreted by prostatic epithelium; it is organ-specific, not cancer-specific.
- Non-cancer causes of raised PSA: benign prostatic hyperplasia, prostatitis, urinary catheterisation, ejaculation and recent prostatic biopsy or instrumentation.
- 5-alpha reductase inhibitors: finasteride and dutasteride lower PSA by about half, so the observed value is doubled after about six months of therapy.
- Gleason score: the sum of the two most common architectural patterns, each graded from 1 to 5, and now reported as grade groups.
- Bone metastases: usually osteoblastic and most often in the axial skeleton, which raises alkaline phosphatase.
- Androgen deprivation: GnRH agonists or antagonists, or surgical orchidectomy; an antiandrogen is given with a GnRH agonist to cover the initial testosterone flare.
- Castration-resistant disease: progression despite castrate testosterone levels, managed with newer androgen pathway inhibitors and docetaxel.
How to work up a raised PSA
A 64-year-old man with a PSA of 9 ng/mL and a firm, asymmetric prostate on examination needs a stepwise assessment before any treatment decision. Each step narrows the diagnosis and avoids unnecessary biopsy.
- Confirm the reading: repeat the PSA after excluding prostatitis, recent catheterisation and ejaculation, because these transiently raise the value.
- Calculate the density: divide PSA by prostate volume measured on transrectal ultrasound, where a density above about 0.15 ng/mL per cc is considered suspicious.
- Check the free fraction: a low free-to-total PSA ratio favours cancer, and cut-offs vary between laboratories.
- Biopsy: after multiparametric MRI where available, a targeted or systematic transrectal or transperineal biopsy provides tissue for histology and Gleason grading.
- Stage the disease: MRI of the prostate and, for high-risk or symptomatic disease, bone scan with alkaline phosphatase to look for metastases.
Density and free fraction are supplementary tools, not stand-alone diagnoses. The final decision rests on the combined PSA trend, examination, imaging and biopsy findings.
Where the exam tries to catch you
Questions on this topic usually test whether the candidate knows which factors change PSA and how Gleason scores are read.
- Trap: a normal PSA excludes prostate cancer. Correct: a substantial proportion of cancers occur with PSA in the normal range, so digital rectal examination and risk assessment remain necessary.
- Trap: a man on finasteride with a low PSA is safe. Correct: the drug lowers PSA by about half, so the measured value must be doubled after six months to reflect the true level.
- Trap: a raised PSA proves cancer. Correct: benign prostatic hyperplasia and prostatitis also raise PSA, so biopsy is needed for confirmation.
- Trap: Gleason 3+4 and 4+3 carry the same prognosis. Correct: 4+3 has a worse prognosis because the higher-grade pattern is predominant.
Frequently asked questions
What does a low free-to-total PSA ratio indicate?
A low free-to-total PSA ratio indicates a higher likelihood of prostate cancer, because PSA produced by cancer is more tightly bound to proteins. The ratio helps decide on biopsy in men whose total PSA lies in the grey zone. Cut-offs vary between laboratories and should be applied together with the clinical picture.
Which bones are most commonly affected by metastatic prostate cancer?
The axial skeleton is most commonly affected by metastatic prostate cancer, particularly the lumbar spine, pelvis and femur. These lesions are usually osteoblastic, which is why alkaline phosphatase often rises. Spinal cord compression is an oncological emergency in these patients.
What is the main hormonal treatment for advanced prostate cancer?
Androgen deprivation therapy is the main hormonal treatment for advanced prostate cancer, given as a GnRH agonist, a GnRH antagonist or surgical orchidectomy. Antiandrogens such as bicalutamide are added at the start of a GnRH agonist to block the initial testosterone flare. Androgen deprivation causes hot flushes, osteoporosis and metabolic changes.
Why does finasteride affect PSA interpretation?
Finasteride affects PSA interpretation because it inhibits 5-alpha reductase, which lowers serum PSA by roughly half in men taking it. Clinicians therefore double the observed PSA value after about six months of treatment. Failure to make this adjustment can delay the diagnosis of a prostate cancer.
What is the difference between Gleason 3+4 and 4+3 prostate cancer?
Gleason 3+4 and 4+3 both total 7, but the predominant pattern differs. Gleason 4+3 carries a worse prognosis than 3+4 because the higher-grade pattern is more extensive. The grade group system now separates these scores into distinct groups for prognosis and treatment decisions.