1. Genitourinary Cancers
Janabel Said
ST4 Clinical Oncology
Ninewells Hospital

2. Topics Renal Cancer Bladder Cancer Prostate Cancer Testicular Cancer
Penile Cancer

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

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

5. 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

6. 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)

7. 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)

8. 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

9. 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

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

11. 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

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

13. 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

14. 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)

15. 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

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

17. 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

18. 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)

19. 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

20. 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

21. 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)

22. 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%)

23. 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

24. 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

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

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

27. 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)

28. 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

29. 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

30. 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)

31. Prostate- confined Disease - treatment

32. 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

33. 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

34. 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)

35. 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

36. 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