Genitourinary Cancers Janabel Said ST4 Clinical Oncology Ninewells Hospital

Topics Renal Cancer Bladder Cancer Prostate Cancer Testicular Cancer Penile Cancer

Renal Cancer 3% of all adult malignancies 30% presenting with metastatic disease M>F, ratio 5:3 50 – 80 years

Renal Tumours Benign, example: adenoma Primary malignant Renal Cell Carcinoma (RCC) Lymphoma Sarcoma Renal Pelvis Transitional Cell Carcinoma Secondary malignant (metastatic)

Renal Cell Carcinoma (RCC) – Risk Factors Smoking Obesity (especially in women) Use of phenacetin analgesics Patients on dialysis, who acquire cystic kidney disease Occupational risk factors Leather tanning (TCC – dye and textile industry) Shoe working Asbestos expsoure Genetic risk factors Von Hippel Lindau disease Tuberous sclerosis Adult polycystic disease

Renal Cell Carcinoma – Clinical Presentation Most are asymptomatic until development of metastasis Classical triad (19% of cases): LOIN PAIN FLANK MASS HAEMATURIA (painless in TCC) Fever and sweats Weight loss Malaise Bone pain if metastatic disease Varicocoele in 2% of males (due to compression of left renal vein) Paraneoplastic syndrome (symptoms that are the consequence of the presence of cancer in the body, but not due to the local presence of cancer cells)

Renal Cell Carcinoma – Clinical Presentation Paraneoplastic syndromes Hypercalcaemia due to PTH-related peptide Polycythaemia due to EPO-like molecules Hypertension due to renin Hepatic dysfunction (unknown mechanism)

Renal Cell Carcinoma - Spread Local Adrenal Glands Renal Veins Inferior Vena Cava Gerota’s fascia (anterior to perinephric space) Perinephric Tissue Lymphatics Lymph nodes at renal hilum Abdominal para-aortic nodes Paracaval nodes Blood Lung Bone Soft tissue Central nervous system skin

Renal Cell Carcinoma – Investigations and Staging Abdominal ultrasound scan CT abdomen – Bosniak 4 part classification uses Hounsefield units to categorise lesions in order of increasing probability of malignancy CT chest and pelvis MRI to image the vena cava Bone scan FBC Biochemistry profile including Calcium levels Renogram if renal impairment present Renal angiography if partial nephrectomy or palliative embolisation are being considered

Renal Cell Carcinoma - Treatment Surgery Radiotherapy (used in Palliative setting) Biological treatment (used in Palliative setting) (Chemotherapy unhelpful)

Renal Cell Carcinoma - Surgery Radical nephrectomy – removal of kidney, adrenal gland, perirenal fat within gerota’s fascia +/- LN dissection Partial (laparoscopic) nephrectomy – when tumour is small, patients have only 1 kidney Palliative nephrectomy – when burden of metastatic disease is small and patient is fit to improve symptoms such as pain and hypercalcaemia for patients being considered for immunotherapy Arterial embolisation Radiofrequency ablation Removal of solitary metastasis

Renal Cell Carcinoma - Radiotherapy Palliative Radiotherapy for symptom control Bone pain Haematuria

Renal Cell Carcinoma – Biological Treatment Cytokine therapy Interferon α Interleukin 2 Signal transduction inhibitors that regulate cell growth, cell proliferation, protein synthesis, and transcription Tyrosine kinase inhibitors Sunitinib Sorafenib Serine/threonine protein kinase inhibitors - MTOR (mammalian target of rapamycin) Temsirolimus Everolimus

Renal Cell Carcinoma - Sunitinib Oral small molecule TK Inhibitor of Vascular endothelial growth factor (VEGF) and Platelet derived growth factor (PDGF) First-line for advanced and/or metastatic renal cell carcinoma Presented at ASCO in 2006: In a phase 3 study - Median progression-free survival: Sunitinib (11 months) vs Interferon α (5 months) Secondary endpoints: 28% of patients had significant tumor shrinkage with Sunitinib compared to 5% with Interferon α. Patients receiving Sunitinib had a better quality of life than interferon α. (N Engl J Med 356 (2): 115–124)

Renal Cell Carcinoma - Sunitinib Side Effects – “dirty drug” Thrombocytopenia Hypertension (+/- proteinuria) Yellow discoloration of the skin Fatigue Gastrointestinal upset (diarrhoea) Left ventricular dysfunction Hypothyroidism Adrenal insufficiency

Bladder Cancer 6% of cancer cases in males 2.5% of cancer cases in females Commoner in Caucasians

Bladder Tumours Benign, example Papilloma and Leiomyoma Carcinoma in situ Primary Malignant Transitional Cell Carcinoma (90%) Squamous Cell Carcinoma (5%) Adenocarcinoma Small Cell Carcinoma Sarcoma Lymphoma Secondary Malignant Direct spread from prostate, cervix or vagina Distant spread

Bladder Cancer – Risk Factors Smoking Occupational risk factors Industrial chemicals such as 2-naphthylamine and acrolein Chronic urinary stasis (increased risk of squamous metaplasia) Long term catheter Bladder stones Paraplegia Chronic infection with Schistosomiasis (squamous cell Ca)

Transitional Cell Carcinoma (TCC) Commonly present in the base of the bladder Multiple tumours are frequent Malignant potential: Low – superficial High – extension into and beyond muscle wall of bladder Low Malignant potential TCC are usually curative High Malignant potential TCC are histologically high grade tumours and >50% of patients will die of their cancers

Transitional Cell Carcinoma – Clinical Presentation Haematuria Minimal haematuria with a proven urinary tract infection present in females doesn’t exclude a co-existent cancer Urgency Dysuria Frequency

Transitional Cell Carcinoma – Investigations and Staging Urinalysis Flexible cystoscopy Renal, urinary tracts and bladder ultrasound scan IVU CT thorax, abdomen and pelvis MRI pelvis Bone scan (bone metastasis present in 5% of cases at presentation)

Transitional Cell Carcinoma – Treatment Rigid Cystoscopy – Transurethral Resection (TURBT) Resection of all visible tumour Additional resection biopsy from the border of the resected area and tumour base for histological assessment of muscle invasion Radical Cystectomy +/- LN dissection Radical Radiotherapy (CI: Hydronephrosis, large tumour bulk and multiple tumours) Neoadjuvant chemotherapy followed by radical cystectomy/ radiotherapy (concurrent chemo-radiotherapy decreases local recurrence rates by 50%)

Prostate Cancer 2nd most common cause of cancer death in men Increased screening has led to increased disease incidence Peak incidence 70 – 75 years Highest incidence is in Western countries

Prostate Tumours Benign Primary Malignant Secondary Malignant Nodular Hyperplasia Primary Malignant Adenocarcinoma (>95%) Transitional Cell Carcinoma Small Cell Carcinoma Squamous Carcinoma Lymphoma Sarcoma Secondary Malignant Direct sspread from Bladder or rectum Metastatic spread

Prostate Cancer – Risk Factors Diet rich in animal fat and proteins Family history

Prostate Cancer – Clinical Presentation Lower urinary tract symptoms Haematuria Perineal pain (rarely) Bone pain (+/- spinal cord compression) Lower limb oedema due to lymphadenopathy

Prostate Cancer - Spread Local Seminal vesicles Base of bladder (spread to rectum is inhibited by the rectoprostatic fascia) Lymphatics Pelvic Lymphadenopathy Para-aortic Lymphadenopathy Blood Bone (most common) Liver (uncommon) Lungs (uncommon) (Brain – virtually unknown)

Prostate Cancer – Investigations and Staging Prostate Specific Antigen PSA (NB: Most aggressive tumours produce little PSA) Transrectal ultrasound guided systematic sampling MRI pelvis for extra-capsular involvement, seminal vesicle invasion CT thorax, abdomen and pelvis (especially for nodal status) Bone scan

Prostate Cancer - Treatment Watch and Wait Policy In patients who are unlikely to develop symptoms Elderly patients (>75 years) Younger patients with serious co-morbidities and good- prognosis tumours Surveillance through regular PSA testing and Digital Rectal Examination

Prostate Cancer – Treatment Prostate – confined disease Radical prostatectomy Interstitial brachytherapy (radioactive iodine seeds) External beam radiotherapy (+/- adjuvant hormonal therapy) Locally advanced disease Neoadjuvant hormone therapy followed by external beam radiotherapy +/- adjuvant hormone therapy Metastatic Disease Hormone therapy Palliative radiotherapy (Bone pain) Palliative Chemotherapy (Docetaxel/Prednisolone)

Prostate- confined Disease - treatment

Prostate Cancer – Hormone Therapy Medical castration via LHRH agonist Example: buserelin, goserelin (given subcutaneously) with anti-androgens for 2 weeks to prevent transient tumour flare Contraindicated in patients with Impending ureteral obstruction Spinal cord compression Painful bone metastasis Anti-androgen therapy Example: cyproterone, bicalutamide (given orally) Toxicity: hot flashes, decreased libido, gynaecomastia, nipple pain, impotence and galactorrhea

Testicular Cancer High cure rate even with metastatic disease First incidence peak at 25 – 35 years and second at 55 – 65 years Types: Germ cell: Seminoma, Teratoma Non Germ cell: Sex cord tumours, mesenchymal tumours, haemopoetic tumours Risk factors: Family history Subnormal testicular development Maldescended testicle Klinefelter’s syndrome Down’s syndrome

Testicular Cancer Clinical Presentation Spread Painless testicular swelling ( and raised ßHCG) Metastatic disease Fatigue Weight loss Shortness of breath due to lung metastasis Ureteric obstruction and renal failure due to lymphadenopathy Local (rare) Lymphatics Inter-aortocaval lymphadenopathy for right sided tumours Para-aortic lymphadenopathy for left sided tumours Pelvic lymphadenopathy Blood Lung (common) Liver (uncommon) Brain (uncommon) Bone (uncommon)

Testicular Cancer – Treatment Testicular-confined disease (example Seminoma): Orchidectomy and adjuvant radiotherapy to para-aortic lymph nodes or adjuvant chemotherapy with single agent carboplatin Infradiaphragmatic Lymphadenopathy: Concurrent chemo-radiotherapy Metastatic Disease: BEP chemotherapy (Bleomycin, cisplatin, etoposide) Relapsed Disease: High Dose chemotherapy with stem cell support

Penile Cancer Associated with HPV infection, subtypes 16 and 18 Squamous Cell Carcinoma Treatments include: Penis-preserving surgery with reconstruction External beam radiotherapy Brachytherapy Laser excision Bilateral Radical Inguinal Lymph Node Dissection Adjuvant concurrent chemo-radiotherapy Concurrent chemo-radiotherapy in locally advanced disease Palliative chemotherapy