Urologic Oncology Update

Dr. Frank Papanikolaou

Urologist, Trillium Health Partners Medical Director of Ambulatory Care, Credit Valley Hospital Tariff Chair, Section of Urology of the OMA Delegate, Credit Valley Medical Society Executive Member at Large of the Canadian Urological Association

Introduction

• Urologic cancers are common and clinically significant

• Family doctors have an integral role in diagnosis, counselling and support for our patients going through cancer treatment

• We value this partnership

Outline

• Prostate• Bladder• Kidney• Testis• Adrenal

Prostate Cancer

Risk Factors for Prostate Cancer Age (median age of 71 years) Family History Geographic location (Northern climates) Race

Caucasians: 16.6% of the men get prostate cancer and 3.5% die African americans: 18.1% get prostate cancer and 4.3 % die

Detection • Most patients are asymptomatic—role of FD is

vital• DRE physical findings

• PSA testing

Canadian Guidelines for Prostate Cancer Screening

• Prostate cancer screening should be offered to all men 50 years of age with at least a 10-year life expectancy

• If there is a family history of prostate cancer or if the patient is of African descent, screening should be offered at age 40 years

• Initial screening should include DRE and PSA • Informed consent regarding the harms and benefits

of PCa screening must be explained to each patient

Canadian Guidelines for Prostate Cancer Screening

• There is no strict PSA screening threshold that should be used for all patients

• It is important to consider PSA velocity, PSA density, and age specific PSA ranges

• The lowest PSA threshold demonstrating a benefit to screening was 2.5 ng/ml

Diagnosis: Transrectal Ultrasound Prostate Biopsy

Histologic Grading

• Gleason Score– Tumors are graded

from 1-5– A higher number

indicates a moreaggressive tumor

– Two most predominantpatterns addedtogether for a scorefrom 2-10

Stage I(A) : low grade, low volume localized

Stage II (B) : localized

Stage III (C) : locally advanced

Stage IV(D) : metastatic

Triaging Treatment

• Patients with a life expectancy of less than 10 years and low grade/ low stage lesions may be candidates for Active Surveillance

• Eradication of the cancer is the goal of therapy in patients with a life expectancy greater than 10 years – Surgery – Radiation

Active Surveillance

The chance of dying of

prostate cancer decreases with:

Lower Gleason score Older age (more competing causes of mortality)

Advantages of Active Surveillance

• Reduces over-treatment of indolent disease

Treatment

• Eradication of the cancer is the goal of therapy in patients with a life expectancy greater than 10 years – Radical Prostatectomy – External-beam Radiation – Brachytherapy

• Decision of treatment modality depends on patient preference, age, and patient comorbidities

Radical Prostatectomy • Surgical removal of the prostate

• Most common side effects are impotence andincontinence

open laparoscopic robotic

External-Beam Radiation • Radiation to the prostate (and pelvis) from

outside the body• Most common side effects are impotence and

rectal irritation• Risks include secondary malignancy

Brachytherapy

HDR – High dose radiation delivered to the prostate through rods implanted temporarily for the procedure

LDR – Low dose radioactive seeds implanted into the prostate permanently which decay over 12 months

Metastatic Prostate Cancer

• Prostate Cancer tends to spread to bone and lymphnodes

• Less commonly, metastatic lesions have been foundin brain, liver and lungs.

• 1941 Charles Huggins showed that advancedprostate cancer was inhibited by decreasingTestosterone (castration or estrogen) andactivated by adding Testosterone.

• 1966 Nobel Prize in Medicine

Treatment of Metastatic Prostate Cancer

Hormone Physiology

• Most androgens areproduced in thetesticles

• Androgens fuel thegrowth of prostate cells,including prostatecancer cells

• Hormone therapy“androgen-deprivationtherapy” cuts off thefuel supply

Hormone Therapies

LHRH agonists (Lupron, Zoladex)

The GnRH antagonists (Degarelix)

Orchiectomy

Anti-androgens (casodex)

Side Effects of ADT (that you might see in your patients)

• Sexual effects: decreased libido and erectile dysfunction

• Physical effects: hot flashes, fatigue, weight gain, hair changes, breast pain, decreased muscle mass, bone mineral density

• Metabolic changes: lipid changes, anemia and diabetes mellitus

• Mental changes: lack of initiative, emotional lability, and decreased memory and cognitive function

Bladder Cancer

Risk Factors for Bladder Cancer • Cigarette smoking: 2-4 fold increased risk

4-Aminobiphenyl O-toluidine

• Industrial dyes – Arylamine exposure

• Chemotherapy – cyclophosphamide

• Pelvic radiation therapy

Cystoscopy for Diagnosis

TURBT

Tumour Stage

Pathology of Bladder Cancer

• 90% Transitional Cell Carcinoma (TCC)

• 5% Squamous cell Carcinoma- more common in Middle East (schistosomiasis, also seen in chronic catheterization

• 0.5%-2% Adenocarcinoma – urachal origin

Treatment of Superficial Bladder Cancer

• BCG given intravesically weekly for six weekcourse

Muscle Invasive Bladder Cancer (Stage T2)

• Radical Cystectomy and Lymph nodedissection-AND:– Males: prostate– Females: anterior exenteration

• Reconstruction:– Ileal conduit– Neobladder– Catheterizable Pouch

N Engl J Med 349;9 859-66 August 28, 2003

Conclusions

• Median survival of cystectomy alone was 46months compared with 77 months forcombination therapy

Kidney Cancer

Kidney Cancer

• Risk Factors – Smoking – Obesity – Exposure to chemicals (asbestos, cadmium,

herbicides, benzene) – HTN – Male – Genetic Risk Factors…

Criteria for referring patients with renal tumours for genetic assessment

Patients with any renal tumour (benign or malignant) AND any one of the following: Bilaterality or multifocality Early age of onset (≤45 years of age) 1st or 2nd degree relative with any renal tumour Skin leiomyomas*, fibrofolliculomas/trichodisomas*

Criteria for referring patients with renal tumours for genetic assessment

One of the following associated tumours: Pheochromocytoma/paraganglioma* Hemangioblastoma of the retina, brainstem, cerebellum or spinal cord* Early onset of multiple uterine fibroids (<30 years of age)* Lymphangiomyomatosis* Childhood seizure disorder*(*or 1st degree relative with same)

Criteria for referring patients with renal tumours for genetic assessment

Patients, with or without RCC, who report a family member (any) with a known clinical or genetic diagnosis of any one of the following:

Von Hippel-Lindau syndrome Birt-Hogg-Dubé syndrome Hereditary leiomyomatosis and renal cell cancer Hereditary papillary renal cell cancer Hereditary paraganglioma/pheochromocytoma Tuberous sclerosis

Pathology

Types of Kidney Cancer • Clear cell is the type of cell that is found in about 70% of

kidney cancers

• Papillary kidney cancer, which develops in 10% to 15% of

patients, is divided into two different subtypes, called type 1

and type 2

• Sarcomatoid is the type of cell that grows the fastest

• Collecting duct is a rare type that behaves in a similar way to

transitional cell carcinoma

• Chromophobe is rare

Treatment • Radical Nephrectomy

• Partial Nephrectomy

Surgical Approaches to Partial and Radical Nephrectomy

Laparoscopic Open Robotic

Minimally Invasive

• Percutaneous Radiofrequency ablation

• Active surveillance

Targeted Therapy for Kidney Cancer

Mechanisms of Action

Regression of Advanced Disease

Conclusions

• We are able to provide comprehensive care for the full gamut of Urologic Cancers and look forward to caring for your patients better together