Prostate Cancer:Prostate Cancer: Causes, Diagnosis, and TreatmentCauses, Diagnosis, and Treatment

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Bruce B. Garber, MD, FACSBruce B. Garber, MD, FACSClinical Associate ProfessorClinical Associate Professor

Drexel University College of MedicineDrexel University College of MedicineGraduate HospitalGraduate HospitalPhiladelphia, PAPhiladelphia, PA

IntroductionIntroduction

The prostate:The prostate:

-is a gland located below the bladder-is a gland located below the bladder

-is only present in men-is only present in men

-surrounds the urethra-surrounds the urethra

-can undergo benign or malignant change-can undergo benign or malignant change

-Urine flows from the bladder through the urethra, -Urine flows from the bladder through the urethra, which is surrounded by the prostate which is surrounded by the prostate-An enlarged prostate can cause difficulty passing urine -An enlarged prostate can cause difficulty passing urine -The prostate is not in the rectum, but can be palpated -The prostate is not in the rectum, but can be palpated during aduring a digital rectal exam digital rectal exam

IncidenceIncidence

-Lung, colon, breast, and prostate cancer are the most -Lung, colon, breast, and prostate cancer are the most

common solid organ cancerscommon solid organ cancers

-Over 200,000 men are diagnosed with prostate -Over 200,000 men are diagnosed with prostate

cancer each year in the U.S.cancer each year in the U.S.

-African-American men have the highest incidence-African-American men have the highest incidence

Prostate Cancer: US Mortality and Incidence, Prostate Cancer: US Mortality and Incidence, 1973–1997 1973–1997

SEER Cancer Statistics Review 1973-1997. National Cancer Institute. Bethesda, MD.

Prostate Cancer: CausesProstate Cancer: Causes

Risk Factors Currently Under Investigation:Risk Factors Currently Under Investigation:

Racial origin: African American > all other races Racial origin: African American > all other races Dietary factors: fatty foods implicatedDietary factors: fatty foods implicated Genetic factors: familial prostate cancer; prostate cancer genes have Genetic factors: familial prostate cancer; prostate cancer genes have

been discoveredbeen discovered

Prostate Cancer: Diagnosis Prostate Cancer: Diagnosis

Methods of Detection:Methods of Detection:

1. Prostate exam (digital rectal exam, DRE)1. Prostate exam (digital rectal exam, DRE)

2. Prostate-specific antigen (PSA) blood test2. Prostate-specific antigen (PSA) blood test

(free, total, complexed, velocity)(free, total, complexed, velocity)

If either is abnormal:If either is abnormal:– Ultrasound-guided prostate needle biopsy Ultrasound-guided prostate needle biopsy

Gleason Pathologic Scoring SystemGleason Pathologic Scoring System for Prostate Cancer for Prostate Cancer

Gleason DF. In: Tannenbaum M, ed. Urologic Pathology: The Prostate. Philadelphia, Pa: Lea & Febiger; 1977:171-197.

Prostate Cancer Staging Systems Prostate Cancer Staging Systems

Stages A, B, C, D Stages A, B, C, D TNM system (stage T1C is most common)TNM system (stage T1C is most common)

Whitmore-Jewett Whitmore-Jewett Classification Stage AClassification Stage A

Microscopic cancer confined to the prostate and too small to be felt by digital rectal exam

A1 Cancer well differentiated and confined to one site

A2 Cancer moderately or poorly differentiated or present in more than one site

Whitmore-Jewett Whitmore-Jewett Classification Stage BClassification Stage B

Cancer large enough to be felt on DRE

B1 Small nodule on one lobe of prostate

B2 Large nodule, several small nodules, or a nodule containing poorly differentiated cells

Whitmore-Jewett Whitmore-Jewett Classification Stage CClassification Stage C

A large cancer involving nearly the entire gland

C1 Cancer may have spread a small distance beyond the gland

C2 Cancer has invaded the neighboring tissue

Whitmore-Jewett Whitmore-Jewett Classification Stage DClassification Stage D

Widespread (metastatic) cancer

D1 Cancer in pelvic lymph nodes

D2 Cancer in bone or other organs

Prostate Cancer: Treatment Options Prostate Cancer: Treatment Options

Non-curative therapies:Non-curative therapies: 1. Androgen deprivation1. Androgen deprivation

-LHRH-agonists-LHRH-agonists-Bilateral orchiectomy-Bilateral orchiectomy-Antiandrogens-Antiandrogens

2. Chemotherapy 2. Chemotherapy 3. Observation3. Observation

Potentially curative therapies:Potentially curative therapies:1. Radical prostatectomy1. Radical prostatectomy

• RetropubicRetropubic• PerinealPerineal• Laparoscopic/RoboticLaparoscopic/Robotic

2. Radiotherapy2. Radiotherapy• External beam radiationExternal beam radiation• Brachytherapy (radioactive seed implant)Brachytherapy (radioactive seed implant)

3. Cryo (freezing)3. Cryo (freezing)

Lupron Depot® is a registered trademark of TAP Pharmaceuticals, Inc.Copyright© 2001 Bayer Corporation. Viadur™ is a trademark of ALZA Corporation under license to Bayer Corporation.Eulexin® is a registered trademark of Schering-Plough Pharmaceuticals.Nilandron is a registered trademark of Aventis.

Non-curative Hormonal Therapy: Non-curative Hormonal Therapy: Currently Available Agents Currently Available Agents

LHRH-agonists:LHRH-agonists: ZoladexZoladex®® (goserelin acetate (goserelin acetate

implant)implant) Lupron DepotLupron Depot®® (leuprolide (leuprolide

acetate for depot suspension)acetate for depot suspension) Viadur™ (leuprolide acetate Viadur™ (leuprolide acetate

implant)implant) EligardEligard®®

Vantas®®

Antiandrogens:Antiandrogens: CasodexCasodex®® (bicalutamide) (bicalutamide) EulexinEulexin®® (flutamide) (flutamide) NilandronNilandron (nilutamide) (nilutamide)

Therapies of Curative Intent:Therapies of Curative Intent:

Radical prostatectomy (total prostate removal)Radical prostatectomy (total prostate removal)– Retropubic (abdominal incision)Retropubic (abdominal incision)– Perineal (incision under scrotum)Perineal (incision under scrotum)– Laparoscopic/Robotic (multiple ports)Laparoscopic/Robotic (multiple ports)

RadiotherapyRadiotherapy– External beam radiationExternal beam radiation– Brachytherapy (radioactive seed implant)Brachytherapy (radioactive seed implant)

Cryoablation (freezing)Cryoablation (freezing)

Radical ProstatectomyRadical Prostatectomy

AdvantagesAdvantages Can remove all the cancerCan remove all the cancer

DisadvantagesDisadvantages Major operationMajor operation Erectile dysfunctionErectile dysfunction IncontinenceIncontinence Scar tissueScar tissue Rectal injuryRectal injury Wound infection, blood clots, Wound infection, blood clots,

heart attack, etc.heart attack, etc. Often doesn’t remove all of the Often doesn’t remove all of the

cancercancer

External Beam Radiation (EBRT)External Beam Radiation (EBRT)

AdvantagesAdvantages Efficacy similar to Efficacy similar to

prostatectomyprostatectomy Outpatient Outpatient

DisadvantagesDisadvantages Erectile dysfunction Erectile dysfunction Chronic bowel and bladder Chronic bowel and bladder

irritation (cystitis, proctitis)irritation (cystitis, proctitis) Requires roughly 7 weeks ofRequires roughly 7 weeks of

daily treatmentdaily treatment Increased risk of Increased risk of rectal & rectal &

bladder cancer!bladder cancer!

Brachytherapy (radioactive seed implant)Brachytherapy (radioactive seed implant)

AdvantagesAdvantages Efficacy similar to EBRT Efficacy similar to EBRT

or surgery or surgery Outpatient; one treatmentOutpatient; one treatment

DisadvantagesDisadvantages Chronic bowel & bladderChronic bowel & bladder

irritationirritation Erectile dysfunctionErectile dysfunction Seed migration 33%Seed migration 33% Can’t treat large prostatesCan’t treat large prostates Increased risk of Increased risk of rectal & rectal &

bladder cancer!bladder cancer!

Cryoablation of the ProstateCryoablation of the Prostate (Cryosurgery, Cryotherapy) (Cryosurgery, Cryotherapy)

CRYO = GREEK WORD FOR COLDCRYO = GREEK WORD FOR COLD

ABLATION = DESTRUCTION ABLATION = DESTRUCTION

What is Cryoablation?What is Cryoablation?

Cryoablation: cancer treatment by freezing toCryoablation: cancer treatment by freezing to-40-40º Centigrade º Centigrade

No surgical incision, minimal blood loss, no radiationNo surgical incision, minimal blood loss, no radiation Immediate cancer cell deathImmediate cancer cell death Dead cells are slowly reabsorbed by the bodyDead cells are slowly reabsorbed by the body Outpatient procedure, with rapid return to normal activitiesOutpatient procedure, with rapid return to normal activities FDA-approved, covered by Medicare & most carriersFDA-approved, covered by Medicare & most carriers New technology: <2% of Urologists currently offering New technology: <2% of Urologists currently offering

CryoablationCryoablation

Transrectal ultrasound guided Transrectal ultrasound guided Transperineal placement of 6-8 Transperineal placement of 6-8

cryo (freezing) probescryo (freezing) probes

Transperineal placement of 5-6 Transperineal placement of 5-6 temperature sensing probestemperature sensing probes

Urethral warming device to Urethral warming device to preserve urethra & limit side preserve urethra & limit side effectseffects

TARGETED CRYOABLATION OF THE PROSTATE (TCAP)

TechnologyTechnology

•Temperature shown in real time•Argon gas freezes prostate rapidly with excellent control

•Two freeze/thaw cycles immediately kill cancer cells

•Total procedure time about 60-90 minutes

•Computer creates “map” of the prostate•Provides real-time guidance•Identifies and guides probe placement

Current Technology:Current Technology:6-8 Probe Argon Cryosurgery System, Total Gland 6-8 Probe Argon Cryosurgery System, Total Gland AblationAblation

6-8 Cryo probes in prostate6-8 Cryo probes in prostate

5-6 Temperature monitoring5-6 Temperature monitoring probesprobes

Argon Gas = rapid response, Argon Gas = rapid response, excellent freeze control excellent freeze control

Helium Gas = rapid thawingHelium Gas = rapid thawing

Prostate Cryoablation

Probes inserted in between scrotum & rectum

Transrectal ultrasound guides the procedure

Targeted Cryoablation of the Prostate (TCAP)

Before Before

Probes Placed Probes Placed

Prostate frozenProstate frozen

Prostate Cryoablation TechniquesProstate Cryoablation Techniques

Total Gland AblationTotal Gland Ablation

Nerve-SparingNerve-Sparing

Focal Focal

Total Prostate CryoablationTotal Prostate Cryoablation

Nerve-Sparing Prostate CryoablationNerve-Sparing Prostate Cryoablation

Focal Prostate CryoablationFocal Prostate Cryoablation

Results of Total Prostate CryoablationResults of Total Prostate Cryoablation

89% of 590 men followed for 7 years were disease-free based on PSA 89% of 590 men followed for 7 years were disease-free based on PSA levels, 87% were disease-free on repeat biopsylevels, 87% were disease-free on repeat biopsy

Rate of rectal injury: 0 - 0.5%Rate of rectal injury: 0 - 0.5%

Rate of urinary incontinence: <5%Rate of urinary incontinence: <5%

Erectile dysfunction common, but can be successfully treated in almost Erectile dysfunction common, but can be successfully treated in almost all menall men

CryoablationCryoablation

AdvantagesAdvantages OutpatientOutpatient Minimally-invasive Minimally-invasive Can treat radiation failuresCan treat radiation failures Can be repeatedCan be repeated Better than radiation for high Better than radiation for high

grade cancer (Gleason 7-10)grade cancer (Gleason 7-10)

DisadvantagesDisadvantages Erectile dysfunctionErectile dysfunction Urinary problems (short-term) Urinary problems (short-term) Shorter track record than surgery Shorter track record than surgery

or radiationor radiation

Summary: Prostate CryoablationSummary: Prostate Cryoablation

A well-established treatment for localized prostate cancerA well-established treatment for localized prostate cancer Covered by Medicare & most carriersCovered by Medicare & most carriers Minimally invasive: no surgical incisionMinimally invasive: no surgical incision Minimal blood loss--blood transfusion not neededMinimal blood loss--blood transfusion not needed Better than radiation for high risk (e.g. high Gleason score) diseaseBetter than radiation for high risk (e.g. high Gleason score) disease Can treat cancer recurrence after radiation (EBRT or seeds)Can treat cancer recurrence after radiation (EBRT or seeds) Does not increase risk of rectal or bladder cancerDoes not increase risk of rectal or bladder cancer Avoids radiation cystitis and proctitisAvoids radiation cystitis and proctitis Avoids seed migration seen with brachytherapyAvoids seed migration seen with brachytherapy Can be combined with hormonal therapyCan be combined with hormonal therapy Outpatient procedure for most menOutpatient procedure for most men Unlike any other treatment, can be repeated if necessaryUnlike any other treatment, can be repeated if necessary Rapid return to normal activitiesRapid return to normal activities More rapid recovery than after radical prostatectomy More rapid recovery than after radical prostatectomy Erectile dysfunction frequent but treatableErectile dysfunction frequent but treatable