3rd Annual Ellis Fischel

Cancer Symposium:

Gentiourinary

Malignancies

Mark R Wakefield, MD, FACS

Chief, Division of Urology

No disclosures

ObjectivesReview top ten updates for the three most

common urologic malignancies

1. Prostate cancer: screening, diagnosis, risk

stratification, and treatment

2. Bladder Cancer: enhanced recovery and

new systemic therapies

3. Renal Cell Carcinoma: systemic and

minimally invasive treatments

1. GU Cancers Are Common

And Potentially Lethal

Prostate Cancer

2. PSA Screening Remains Controversy

Early diagnosis at lower stage

Better cure with more options

Over-diagnosis with over-treatment

No survival benefit

Harm and side-effects from treatment

Prostate Cancer Incidence

Decreasing mortality rate

Prostate Cancer: PSAContradictions regarding utility in recent data

– PLCO (US screening trial)• Increased diagnosis of prostate cancer in screen

– 22% more by 7 years

• No identified survival benefit

• High cross-over

– Some details• 77,000 patients aged 55-74 (1993-2001; 2006)

• 52% of control had PSA and 40% had DRE

• 85% screened with PSA and 86% with DRE

• Increased death in screened group: 50 v 44 (ns)

NEJM 2009; 360:1310-1328

Prostate Cancer: PSA

Prostate Cancer: PSA

Contradictions in recent data

– ERSPC (European screening and treatment trial)

• 162,000 55-69 year old men for 9 year median follow-up

• Screened group with PSA every 4 years

– 82% of men in screening group received PSA

– 16% with elevated PSA

– 17,500 biopsies

– 8.2% diagnosis in screened group and 4.8% in control

• 20% reduction in mortality (27% for those actually screened)

– 214 deaths in screened

– 326 deaths in control

• 1410 men screened per year for one death prevented

• 48 men require treatment to prevent one death

NEJM 2009; 360:1320-1328

Prostate Cancer: PSAContradictions in recent data

ERSPC (European screening and treatment trial)

Prostate Cancer: PSA• Recommendations:

– ACS and AUA : Offer annual DRE and PSA, greater than 50 (40) years of age and 10-year life expectancy

– ACP and AMA: Provide risk and benefit discussion; individualize screen based on patient

– USPSTF: Screening recommended based on individual assessment • C recommendation for men aged 55 to 69 (2018)

• Inadequate data to support: grade D (2012)

• Recommends against men over age of 75 (70 in draft)

(Annals of Internal Medicine, 149, 192-199; 2008)

Prostate Cancer

3. Better Tools for Diagnosis

Biopsies has significant risk

>150 targeted biopsies at Ellis Fischel

Prostate CancerMRI for identifying high risk prostate cancer

• 3Tesla multi-parametric

• Dynamic contrast enhanced

• Diffusion-eeighted images

• PI-RADS risk score

• Pre-biopsy tool– Sensitivity = 0.85 (95% CI 0.78-0.91)

– Specificity = 0.71 (95% CI 0.60-0.80)

Prostate Cancer

55 yo M, Gleason 7 (4 + 3) PZ

prostate cancer

Tumor extension to seminal vesicles

Looking for wall thickening, obliteration of lumina

A. Diffuse B. Focal

Prostate Cancer: Targeted

Biopsy directed to MRI identified lesion

Prostate Cancer

4. Improved Risk Stratification

Identification of low risk disease

Active Surveillance

Identification of high risk disease

Multimodal therapy

Early identification of metastatic disease

Directed local and systemic therapy

Prostate Cancer Biomarkers

Tissue based

• Decipher

• Prolaris

• OncotypeDx

• ConfirmMDx

Liquid based

• PSA

• PCA3

• 4K score

• Prostate Health

Index

• Apifiny

Prostate Cancer Imaging

• Radio-nucleotide imaging

– Axumin

Fluciclovine F18

– PSMA-PET

Ga-68-PSMA-11

Prostate Cancer

5. Prostate Cancer Treatment Matures

Increased active surveillance

Application of robotic prostatectomy

Expansion of systemic treatments

Prostate Cancer: Treatment

Robotic Prostatectomy: 80% of Cases in United States

Prostate Cancer: Treatment

Robotic Prostatectomy: 80% of Cases in United States

Prostate Cancer: progressionSystematic therapies for metastatic disease

– Androgen Deprivation: intermittent versus continuous

– Secondary hormonal therapies

• Anti-androgens: uncertain role of earlier generations (bicalutamide)

• Newer: abiraterone, enzalutamide, apalutamide

- M0 castrate resistance: apalutamide and enzalutamide

- M1 castrate sensitive: abiraterone

– Taxol and similar therapies (cabazitaxel): promising and tolerated well• Primary treatment prior to castrate resistance for metastatic

disease

• Neo-adjuvant role

– Immunotherapy: Provenge

– Radiotherapy: Radium 223

Kidney Cancer

6. Increased incidence in US

– Demographic risk factors

– Small renal mass incidentally detected

7. Application of minimal invasive therapies

– Needle biopsy

– Active surveillance

– Ablative therapies

– Robotic assisted laparoscopy for partial

Renal Cell CarcinomaKunkle, DA, et al, Journal of Urology, 179: 1227; April 2008

• Incidentally detected renal mass

– Up to 70% of new diagnosis

– Earlier stage at diagnosis

– Increased surgical treatment

– Minimal change in overall surviva

• Imaging accurately diagnosis pathology

in most cases (95% PPV)

Renal Cell CarcinomaLipworth, L, et al, Journal of Urology, 176: 2353; December 2006

6. Suspected risk

factors• Cigarette Smoking

• Obesity

• Hypertension

• Analgesics

• Diet

• Alcohol

• Occupational Exposure

• Immunosuppression

Renal Cell CarcinomaLane, BR, et al, Journal of Urology, 179: 20; January 2008

7. Re-evaluation of the role of biopsy of renal mass– CT-guided, percutaneous biopsy

– 18 gauge true-cut

– 5% minor and major complication rate

– Insufficient biopsy material in 5-10%

– False negative biopsy 10-50%

– Indications:• Metastatic disease to kidney

• Metastatic renal cell

• Bilateral

• Contraindication to surgery

Renal Cell CarcinomaKunkle, DA, et al, Journal of Urology, 179: 1227-33, April 2008

Treatment options:

– Partial nephrectomy

• Laparoscopic/ robotic

• Open

– Open or laparoscopic or

percutaneous cryoablation

– Percutaneous

radiofrequency ablation

– Open or lap total

nephrectomy

– Surveillance

– HIFU

– Radiotherapy

Kidney Cancer8. Advanced disease at progression

– Vascular involvement: IVC thrombectomy

– Re-defining role of cytoreductive nephrectomy

– Neoadjuvant and adjuvant therapies

– Rapid expansion of therapies for metastatic disease

Bladder CancerTale of two diseases

– High prevalence due to recurrent non-invasive disease

– High mortality and morbidly for muscle invasive disease

9. Urinary diversion history and advances

10. Advanced recovery and robotic applications promise

improved recovery

Historical BackgroundBladder Substitution After Pelvic Exenteration

Surgical Clinics of North America, 1950

Eugene M. Bricker

9. Types of DiversionIleal Conduit

Types of DiversionIleal Neobladder

Bladder Cancer: RC-TIGER

– Better prepared for surgery

– Shorter and safer hospital stay

• Less CV and VTE risk

• Shorter hospital stay: earlier recovery of bowel

function

• Better functional capacity upon discharge:

RIOT

• Lower infection rate

• Fewer complications and readmissions

• Improved patient satisfaction

10. TIGER-RCPilot results (35 cases):

4 day shorter LOS (128)

80% fewer ICU days

Urologic Oncology at Ellis Fischel

• Multi-Disciplinary team

• Multiple therapeutic options

• Available trials

• Advanced therapies