Urological cancers

Renal cell carcinoma

• Arises from proximal convoluted tubule epithelium. Clear cell RCC (about 75%) shows nests of cells with clear, glycogen- and lipid-rich cytoplasm in a delicate vascular network; it follows loss of the VHL gene on chromosome 3p. Papillary and chromophobe types are less common. A tumour of the renal pelvis causing haematuria is usually urothelial carcinoma, not RCC.
• Risks: smoking (strongest), obesity, hypertension, long-term dialysis (acquired cystic disease), von Hippel–Lindau (bilateral, multiple), tuberous sclerosis, cadmium.
• Presentation: mostly incidental; classic triad of haematuria, loin pain and flank mass in only about 10%. RCC loves veins: it spreads through the bloodstream, grows into the renal vein and IVC, causes a left varicocele that does not empty on lying (left gonadal vein drains into the left renal vein), and seeds cannonball lung and lytic bone metastases.
• Paraneoplastic: polycythaemia (erythropoietin), hypercalcaemia (PTHrP), hypertension (renin), Stauffer syndrome (non-metastatic liver dysfunction), fever.
• Contrast CT is the investigation of choice. Radical or partial nephrectomy; RCC resists conventional chemotherapy and radiotherapy, so metastatic disease is treated with tyrosine kinase inhibitors and immunotherapy.

Bladder cancer

• Carcinogens are absorbed, conjugated in the liver and excreted in urine, so the whole urothelium is exposed. This field change explains multifocal tumours and recurrence in the renal pelvis, ureter and bladder.
• Painless visible haematuria is the classic presentation. In a 62-year-old smoker the standard work-up is flexible cystoscopy (bladder) plus CT urography (kidneys and upper tracts), with urine culture, cytology and renal function.
• About 75% are non-muscle-invasive (Ta, T1, carcinoma in situ): TURBT, a single dose of intravesical mitomycin, intravesical BCG for high-grade disease and CIS, and lifelong cystoscopic surveillance. Muscle-invasive (T2 or more): neoadjuvant cisplatin then radical cystectomy with ileal conduit or neobladder, or chemoradiotherapy.

Prostate cancer

• Adenocarcinoma of the peripheral zone (posterior, felt on rectal examination; classically the posterior lobe). BPH arises in the transition zone (median and lateral lobes), so it causes early urinary symptoms and a smooth, firm, enlarged gland.
• Risks: age, black ethnicity, family history, BRCA2, Lynch syndrome.
• PSA is organ-specific, not cancer-specific: raised by BPH, prostatitis, UTI, retention, catheterisation and ejaculation; halved by finasteride. A PSA of 3.5 ng/mL with a smooth firm enlarged gland and LUTS fits BPH; a hard nodule fits cancer.
• Diagnosis: multiparametric MRI before biopsy, then targeted transperineal biopsy; grading by Gleason score (ISUP Grade Groups 1–5).
• Bone metastases are osteoblastic (sclerotic): tumour cells secrete factors (endothelin-1, BMPs, Wnt signals) that stimulate osteoblasts to lay down new bone, so vertebrae and pelvis look dense and white and ALP rises. Spread to vertebrae and skull is via the valveless vertebral venous plexus (Batson). Myeloma, in contrast, is purely lytic and may be invisible on bone scan.
• Metastatic cord compression: dexamethasone, urgent MRI, radiotherapy or surgery.
• Treatment: low risk active surveillance; localised disease radical prostatectomy (erectile dysfunction, incontinence) or radiotherapy with hormones. Advanced: androgen deprivation. GnRH agonists (goserelin) cause a testosterone flare in the first weeks, so an anti-androgen (bicalutamide) is started first; GnRH antagonists (degarelix) and orchidectomy give no flare. Add abiraterone, enzalutamide or docetaxel.

Testicular tumours

• Commonest solid cancer in men aged 15–35; over 90% are germ cell tumours and most are curable even when metastatic.
• Risks: cryptorchidism (risk persists after orchidopexy and affects the other testis too), previous testicular cancer, family history, Klinefelter syndrome, germ cell neoplasia in situ.

• Teratoma in adults behaves differently from children: in prepubertal boys mature teratoma is benign, but a post-pubertal teratoma is malignant even if every tissue is mature (cartilage, gut, skin), because it arises from germ cell neoplasia in situ and can metastasise. After chemotherapy for a mixed tumour, a growing residual mass with falling markers is usually teratoma ("growing teratoma syndrome") and needs excision, since it is chemoresistant.
• LDH reflects tumour bulk. A raised AFP in a "seminoma" means non-seminomatous elements and changes treatment.
• Presentation: painless firm lump within the testis, dragging sensation, secondary hydrocele, back pain from nodes; occasionally acute pain from haemorrhage.
• Lymphatics follow the testicular vessels to the para-aortic nodes at L1–L2, not to inguinal nodes, unless the scrotal skin is involved.
• Work-up: scrotal ultrasound, markers before surgery (AFP, hCG, LDH), CT staging. Treatment: radical inguinal orchidectomy with high cord ligation; never a scrotal incision or biopsy (it opens new lymphatic routes to the inguinal nodes). Then surveillance, carboplatin or radiotherapy for seminoma, BEP chemotherapy (bleomycin lung toxicity), retroperitoneal node dissection for residual masses.
• Radiosensitivity, highest first: lymphoma, seminoma, then glioma.

Remember Seminoma: no AFP, very radiosensitive. Yolk sac: AFP. Choriocarcinoma: hCG. Old man: lymphoma.

Exam trap A pure mature teratoma in an adult testis is still malignant and can metastasise.

Exam trap Prostate metastases look dense because they make bone; do not mistake sclerosis for healing.

Penile cancer

• Squamous cell carcinoma linked to HPV, phimosis and lack of circumcision, smoking and lichen sclerosus; spreads to inguinal nodes.

How FCPS asks about this

• Painless visible haematuria in a smoker: flexible cystoscopy plus CT urography.
• Occupational bladder carcinogen: aromatic amines in dye and rubber industries; schistosomiasis causes squamous carcinoma.
• Clear glycogen-rich renal tumour cells: proximal tubular epithelium (clear cell RCC, VHL); RCC spreads by blood and invades the renal vein.
• Dense vertebral metastases in prostate cancer: osteoblastic, because tumour stimulates new bone formation; spread via the vertebral venous plexus.
• Lobe or zone involved: cancer in the peripheral (posterior) zone; BPH in the transition zone.
• Testicular markers: AFP never raised in pure seminoma; AFP in yolk sac tumour; hCG in choriocarcinoma; lymphoma over 60.
• Mature teratoma in a 28-year-old: can metastasise despite mature tissue; first nodes involved are para-aortic.