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