Genitourinary Cancers

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Genitourinary Cancers

• Janabel Said
• ST4 Clinical Oncology
• Ninewells Hospital

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Topics

• Renal Cancer
• Bladder Cancer
• Prostate Cancer
• Testicular Cancer
• Penile Cancer

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Renal Cancer

• 3 of all adult malignancies
• 30 presenting with metastatic disease
• MgtF, ratio 53
• 50 80 years

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Renal Tumours

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

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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

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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)

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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)

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Renal Cell Carcinoma - Spread

• Local
• Adrenal Glands
• Renal Veins
• Inferior Vena Cava
• Gerotas 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

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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

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Renal Cell Carcinoma - Treatment

• Surgery
• Radiotherapy (used in Palliative setting)
• Biological treatment (used in Palliative setting)
• (Chemotherapy unhelpful)

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Renal Cell Carcinoma - Surgery

• Radical nephrectomy removal of kidney, adrenal
  gland, perirenal fat within gerotas 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

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Renal Cell Carcinoma - Radiotherapy

• Palliative Radiotherapy for symptom control
• Bone pain
• Haematuria

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Renal Cell Carcinoma Biological Treatment

• Cytokine therapy
• Interferon a
• 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

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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 a (5 months)
• Secondary endpoints 28 of patients had
  significant tumor shrinkage with Sunitinib
  compared to 5 with Interferon a.
• Patients receiving Sunitinib had a better quality
  of life than interferon a.
• (N Engl J Med 356 (2) 115124)

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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

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Bladder Cancer

• 6 of cancer cases in males
• 2.5 of cancer cases in females
• Commoner in Caucasians

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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

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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)

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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 gt50 of patients will die
  of their cancers

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Transitional Cell Carcinoma Clinical
Presentation

• Haematuria
• Minimal haematuria with a proven urinary tract
  infection present in females doesnt exclude a
  co-existent cancer
• Urgency
• Dysuria
• Frequency

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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)

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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)

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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

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Prostate Tumours

• Benign
• Nodular Hyperplasia
• Primary Malignant
• Adenocarcinoma (gt95)
• Transitional Cell Carcinoma
• Small Cell Carcinoma
• Squamous Carcinoma
• Lymphoma
• Sarcoma

• Secondary Malignant
• Direct sspread from Bladder or rectum
• Metastatic spread

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Prostate Cancer Risk Factors

• Diet rich in animal fat and proteins
• Family history

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Prostate Cancer Clinical Presentation

• Lower urinary tract symptoms
• Haematuria
• Perineal pain (rarely)
• Bone pain (/- spinal cord compression)
• Lower limb oedema due to lymphadenopathy

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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)

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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

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Prostate Cancer - Treatment

• Watch and Wait Policy
• In patients who are unlikely to develop symptoms
• Elderly patients (gt75 years)
• Younger patients with serious co-morbidities and
  good- prognosis tumours
• Surveillance through regular PSA testing and
  Digital Rectal Examination

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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)

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Prostate- confined Disease - treatment
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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

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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
• Klinefelters syndrome
• Downs syndrome

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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)

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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

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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