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Janabel SaidST4 Clinical Oncology
Ninewells Hospital
Topics
Renal CancerBladder CancerProstate CancerTesticular CancerPenile Cancer
Renal Cancer3% of all adult malignancies
30% presenting with metastatic disease
M>F, ratio 5:3
50 – 80 years
Renal TumoursBenign, example: adenoma
Primary malignantRenal Cell Carcinoma (RCC)LymphomaSarcomaRenal Pelvis Transitional Cell Carcinoma
Secondary malignant (metastatic)
Renal Cell Carcinoma (RCC) – Risk FactorsSmokingObesity (especially in women)Use of phenacetin analgesicsPatients on dialysis, who acquire cystic kidney diseaseOccupational 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 PresentationMost are asymptomatic until development of metastasisClassical triad (19% of cases):
LOIN PAINFLANK MASSHAEMATURIA (painless in TCC)
Fever and sweatsWeight lossMalaiseBone pain if metastatic diseaseVaricocoele 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 peptidePolycythaemia due to EPO-like moleculesHypertension due to reninHepatic dysfunction (unknown mechanism)
Renal Cell Carcinoma - SpreadLocal
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 StagingAbdominal ultrasound scanCT abdomen – Bosniak 4 part classification uses Hounsefield
units to categorise lesions in order of increasing probability of malignancy
CT chest and pelvisMRI to image the vena cavaBone scanFBCBiochemistry profile including Calcium levelsRenogram if renal impairment presentRenal 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
fitto improve symptoms such as pain and hypercalcaemia for patients being considered for immunotherapy
Arterial embolisationRadiofrequency ablation Removal of solitary metastasis
Renal Cell Carcinoma - RadiotherapyPalliative Radiotherapy
for symptom control Bone painHaematuria
Renal Cell Carcinoma – Biological Treatment
Cytokine therapyInterferon αInterleukin 2
Signal transduction inhibitors that regulate cell growth, cell proliferation, protein synthesis, and transcriptionTyrosine 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 - SunitinibSide Effects – “dirty drug”
ThrombocytopeniaHypertension (+/- proteinuria)Yellow discoloration of the skinFatigueGastrointestinal upset (diarrhoea) Left ventricular dysfunctionHypothyroidismAdrenal insufficiency
Bladder Cancer
6% of cancer cases in males
2.5% of cancer cases in females
Commoner in Caucasians
Bladder TumoursBenign, example Papilloma and Leiomyoma
Carcinoma in situ
Primary MalignantTransitional Cell Carcinoma (90%)Squamous Cell Carcinoma (5%)AdenocarcinomaSmall Cell CarcinomaSarcomaLymphoma
Secondary MalignantDirect spread from prostate, cervix or vaginaDistant spread
Bladder Cancer – Risk Factors
SmokingOccupational risk factors
Industrial chemicals such as 2-naphthylamine and acroleinChronic urinary stasis (increased risk of squamous
metaplasia)Long term catheterBladder stonesParaplegia
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
HaematuriaMinimal haematuria with a proven urinary tract infection
present in females doesn’t exclude a co-existent cancerUrgencyDysuriaFrequency
Transitional Cell Carcinoma – Investigations and Staging
Urinalysis Flexible cystoscopyRenal, urinary tracts and bladder ultrasound scanIVUCT thorax, abdomen and pelvisMRI pelvisBone scan (bone metastasis present in 5% of cases at
presentation)
Transitional Cell Carcinoma – TreatmentRigid Cystoscopy – Transurethral Resection (TURBT)
Resection of all visible tumourAdditional resection biopsy from the border of the resected
area and tumour base for histological assessment of muscle invasion
Radical Cystectomy +/- LN dissectionRadical 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 TumoursBenign
Nodular Hyperplasia
Primary MalignantAdenocarcinoma (>95%)Transitional Cell
CarcinomaSmall Cell CarcinomaSquamous CarcinomaLymphomaSarcoma
Secondary MalignantDirect sspread from
Bladder or rectumMetastatic spread
Prostate Cancer – Risk Factors
Diet rich in animal fat and proteins
Family history
Prostate Cancer – Clinical Presentation
Lower urinary tract symptomsHaematuriaPerineal pain (rarely)Bone pain (+/- spinal cord compression)Lower limb oedema due to lymphadenopathy
Prostate Cancer - SpreadLocal
Seminal vesiclesBase of bladder(spread to rectum is inhibited by the rectoprostatic fascia)
LymphaticsPelvic LymphadenopathyPara-aortic Lymphadenopathy
BloodBone (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 PolicyIn 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 prostatectomyInterstitial 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 DiseaseHormone therapyPalliative 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
flareContraindicated in patients with
Impending ureteral obstruction Spinal cord compression Painful bone metastasis
Anti-androgen therapyExample: cyproterone, bicalutamide (given orally)Toxicity: hot flashes, decreased libido, gynaecomastia, nipple
pain, impotence and galactorrhea
Testicular CancerHigh cure rate even with metastatic diseaseFirst incidence peak at 25 – 35 years and second at 55 – 65
yearsTypes:
Germ cell: Seminoma, TeratomaNon Germ cell: Sex cord tumours, mesenchymal tumours,
haemopoetic tumoursRisk factors:
Family historySubnormal testicular development
Maldescended testicle Klinefelter’s syndrome Down’s syndrome
Testicular CancerClinical Presentation SpreadPainless testicular swelling
( and raised ßHCG)Metastatic disease
FatigueWeight lossShortness of breath due to
lung metastasisUreteric 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 lymphadenopathyBlood
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 CancerAssociated with HPV infection, subtypes 16 and 18Squamous Cell CarcinomaTreatments include:
Penis-preserving surgery with reconstructionExternal beam radiotherapyBrachytherapyLaser excisionBilateral Radical Inguinal Lymph Node DissectionAdjuvant concurrent chemo-radiotherapyConcurrent chemo-radiotherapy in locally advanced
diseasePalliative chemotherapy