Transcript 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
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Leather tanning (TCC – dye and textile industry)
Shoe working
Asbestos expsoure
 Genetic risk factors
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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
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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
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Sunitinib
Sorafenib
 Serine/threonine protein kinase inhibitors - MTOR
(mammalian target of rapamycin)
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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 chemoradiotherapy 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
 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
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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
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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
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Maldescended testicle
Klinefelter’s syndrome
Down’s syndrome
Testicular Cancer
Clinical Presentation
Spread
 Painless testicular swelling (
 Local (rare)
and raised ßHCG)
 Metastatic disease
 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)
 Fatigue
 Weight loss
 Shortness of breath due to
lung metastasis
 Ureteric obstruction and renal
failure due to
lymphadenopathy
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