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Genitourinary Cancers

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Genitourinary Cancers Powered By Docstoc
					         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
    Nodular Hyperplasia


 Primary Malignant           Secondary Malignant
    Adenocarcinoma (>95%)       Direct sspread from
    Transitional Cell            Bladder or rectum
     Carcinoma                   Metastatic spread
    Small Cell Carcinoma
    Squamous Carcinoma
    Lymphoma
    Sarcoma
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 (        Local (rare)
  and raised ßHCG)                      Lymphatics
 Metastatic disease                       Inter-aortocaval
     Fatigue                               lymphadenopathy for right
     Weight loss                           sided tumours
     Shortness of breath due to           Para-aortic lymphadenopathy
      lung metastasis                       for left sided tumours
     Ureteric obstruction and renal       Pelvic lymphadenopathy
      failure due to                    Blood
      lymphadenopathy                      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