Bladder Stone

Prostate cancer is predominantly adenocarcinoma arising from prostatic glandular epithelium.

Disease ranges from indolent low grade tumours requiring no immediate treatment to rapidly progressive metastatic cancer.

Risk assessment combines:

• PSA
• Clinical stage
• Histological grade
• Tumour volume
• Imaging
• Life expectancy

ISUP Grade Groups

Grade Group 1

Gleason 3 + 3 = 6.

Grade Group 2

Gleason 3 + 4 = 7.

Grade Group 3

Gleason 4 + 3 = 7.

Grade Group 4

Gleason score 8.

Grade Group 5

Gleason 9 to 10.

The distinction between 3 + 4 and 4 + 3 is clinically important because predominant Gleason pattern 4 confers substantially greater risk.

Localised prostate cancer is usually asymptomatic.

Possible presentations include:

• Raised PSA
• Abnormal DRE

Advanced disease can produce:

• Bone pain
• Weight loss
• Haematuria
• Urinary obstruction
• Hydronephrosis
• Pathological fracture
• Spinal cord compression

New back pain with weakness or sphincter symptoms in a man with advanced prostate cancer requires emergency assessment for metastatic spinal cord compression.

PSA is organ specific but not cancer specific.

Elevation also occurs with:

• BPH
• Prostatitis
• UTI
• Acute urinary retention

A moderately elevated PSA should usually be confirmed before biopsy where the clinical situation permits.

Multiparametric prostate MRI: perform before biopsy in suspected organ confined disease.

Suspicious MRI lesions undergo targeted biopsy with appropriate systematic or perilesional sampling.

The transperineal route reduces infectious complications compared with traditional transrectal biopsy and is increasingly preferred.

For unfavourable intermediate or high risk disease, PSMA PET/CT provides superior staging accuracy when available.

Treatment depends on:

• Grade group
• Stage
• PSA
• Expected survival
• Patient preference

Low risk disease

For men with life expectancy above approximately 10 years, active surveillance is generally preferred.

Surveillance uses:

• PSA
• MRI
• Repeat biopsy according to protocol

Treatment begins if disease is reclassified rather than treating every Grade Group 1 tumour immediately. Long term cancer specific survival under appropriately selected active surveillance is excellent.

Localised intermediate risk disease

Curative options include:

• Radical prostatectomy
• External beam radiotherapy
• Brachytherapy in selected disease

Unfavourable intermediate disease treated with radiotherapy generally receives short term androgen deprivation for approximately 4 to 6 months.

High risk and locally advanced disease

Options include:

• Radical prostatectomy as part of multimodal treatment in selected men
• External beam radiotherapy plus long term ADT
• Additional systemic intensification in appropriate very high risk disease

Radical prostatectomy removes:

• Entire prostate
• Seminal vesicles

followed by vesicourethral anastomosis.

Important complications include:

• Urinary incontinence
• Erectile dysfunction
• Anastomotic stricture
• Lymphocele after lymph node dissection

Androgen deprivation

Options include:

• Bilateral orchiectomy
• LHRH agonist
• LHRH antagonist

LHRH agonists can cause an initial testosterone flare.

Where immediate suppression is essential, such as impending cord compression or major bladder outlet obstruction, use an LHRH antagonist or orchiectomy rather than allowing a flare.

Metastatic hormone sensitive disease

ADT alone is inadequate treatment for most fit patients.

Combine ADT with an androgen receptor pathway inhibitor such as:

Abiraterone 1000 mg orally once daily

plus

Prednisone or prednisolone approximately 5 mg once daily

or:

Enzalutamide 160 mg orally once daily

or another approved AR pathway agent.

Selected fit patients, particularly those with substantial metastatic burden, may receive triplet treatment incorporating docetaxel.

Metastatic castration resistant disease

Continue castration level androgen suppression.

Treatment is selected according to previous therapy and molecular profile and can include:

• Abiraterone
• Enzalutamide
• Docetaxel
• Cabazitaxel
• PARP inhibitor for appropriate HRR altered disease
• Lutetium PSMA radioligand therapy in selected PSMA positive disease
• Radium 223 for selected symptomatic bone predominant disease without visceral metastases

A standard docetaxel regimen is:

Docetaxel 75 mg/m² IV every 3 weeks

with appropriate steroid support, commonly up to 10 cycles in mCRPC.

Molecular testing for BRCA1, BRCA2 and other homologous recombination repair alterations increasingly affects advanced treatment selection.