PROSTATE CANCER - 2012

• 241,740 new cases

• 29 % of all new male cancer cases

• 28,170 deaths

• Lifetime risk of prostate cancer 1:5

2012 Estimates – American Cancer Society

INC

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NC

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S

PROSTATE CANCER

050,000

100,000150,000200,000250,000300,000350,000

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19921994199619982000200220042006200820102012

Year

New CasesDeaths

PROSTATE CANCER

• 30% of men > 50 years old have CaP at autopsy

• Lifetime risk of malignancy in 50y/o - 42%

• Lifetime risk of CLINICAL CaP - 19 %

• Risk of dying from CaP - 2.9%

• UNIQUE DISCREPANCY OF PREVALENCE versus CLINICAL

U.S. Preventive Services Task Force(Draft report: 10/11/2011)

• Recommends against screening for prostate specific antigen

• Moderate or high certainty that no net benefit or harms outweigh benefits

• Grade D recommendation – discourage the use of this service- applies to all

healthy men.

U.S. Preventive Services Task Force(Draft report: 10/11/2011)

• Relied heavily on meta-analyses combining high and low quality evidence

• Used overall mortality rather than cancer specific mortality

• Considered only intention to treat

• Did not consider risk stratification or longer duration of followup

USPSTF on Prostate Ca Screening: FINAL REPORT

• Class D recommendation: Screening for prostate cancer should be actively discouraged

• Committee of primary care physicians; headed by pediatrician

• No Urological or Oncology consultants

• Same group: No mammograms age 40-50

Promulgated May, 2012

Effect of USPSTF Recommendation on Metastatic Prostate Ca

• SEER data 1983-1995 vs. 2006-2008

• Adj. for age, race, geographic variation

• Computed # of men who presented w/ M1 in SEER 9 registries area in 2008

• Expected/observed ratio M1 in 2008 = 3.1

• If USPSTF rec. applied to US population =

25,000 vs. 8000 CaP pts. with metastases

Scosyrev E…Messing EM. Cancer Online (July 30, 2012)

PLCO - CaP Screening Trial• 76,693 men• Randomized to annual screen vs. usual practice• At 7-10 years, death rate low and not different

Findings per 10,000 pt. yrs.

Screened

(38,343 pts.)

Control

(38,350 pts.)

Incidence of CaP

116

(2820 cancers)

95

(2322 cancers)

CaP Deaths 2.0 (50 deaths) 1.7 (44 deaths)

Andriole GL et al NEJM 360:1310, 2009.

PLCO - CaP Screening Trial

• Contamination (40-52%)

• # of patients “pre-screened”

• Short followup for mortality

• Wide confidence bars

• Percent of controls with higher stage/grade

Andriole GL et al NEJM 360:1310, 2009.

EORTC Randomized CaP Screening Study

• 162,387 men age 55-69 years• Screened every 4 years; cutpoint PSA > 3.0• * 20% reduction in CaP deaths ( p = 0.04)

Findings Screened

(72, 890 pts)

Control

(89,353 pts)

Incidence CaP 8.2% 4.8%

CaP Deaths 214* 326*

Schroder FH et al. NEJM 360:1320, 2009.

EORTC Randomized CaP Screening Study - Conclusions

• High rate of overdiagnosis (8.2 vs. 4.8%)

• PSA screening reduced CaP deaths (p =.04)

• Death risk difference 0.71/1000 men

• 1410 men screened/48 Rx to prevent 1 death

• Benefit of screening: Age 55-69 years

• 41% reduction in adverse features (p <0.001)

Schroder FH et al. NEJM 360:1320, 2009.

Göteborg CaP Screening Study

• Randomized population-based 1:1 (59 y/o)

• 20,000 men PSA testing every 2 years

• Median followup 14 years

• Dx CaP: 12.7% vs 8.2% (p < 0.0001)

• CaP deaths 0.56 in screened men (p=0.002)

• 293 screened; 12 dx to prevent 1 CaP death

Hugosson J et al . Lancet Oncol 11: 725, 2010.

CONCLUSIONS

• Careful analysis SUPPORTS screening for CaP

• Problem is overtreatment, not overdiagnosis

• Better predictors of aggressiveness would limit overtreatment

• Less morbid therapies would diminish problems with overtreatment

• Controversies about prostate cancer will persist

12-core Biopsy Technique

Gleason Pathologic Grading System

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

X

X

Clinical T(umor) Stage

• T1a/b – Incidental CaP after TURP

• T1c - Discovered by PSA; no nodule

• T2a – Prostate nodule < ½ of 1 side

• T2b – Prostate nodule > ½ of 1 side

• T2c – Prostate nodules both sides

• T3a – CaP through capsule 1 or both sides

• T3b – Seminal vesicle invasion

RISK STRATIFICATIONRisk Grp. PSA Gleason T-stage

Low 10 & 7 & T1c/T2a

Intermed. 10-20 or 7 or T2b

High >20 or 8-10 or T2c /+

or > 2 ng in past year

PROSTATE CANCERMgt: LOCALIZED CaP

• Active Surveillance

• Radical Radiation Therapy

• Radical Prostatectomy

• Factors:• Age and health of patient

• Extent of disease

• Morbidity

Watchful Waiting - Localized CaP

Albertson PC et al. JAMA 293:2095-2101, 2005

Active Surveillance - Candidates

• > age 70-75 (?? Age 65 +)

• Intercurrent illness or comorbidities

• Gleason 3 +3 on few biopsies

• Low stage (T2 or <)

• Low PSA with slow rise on serial study

• Understand need for periodic biopsies

Watchful Waiting vs. RRP

Bill-Axelson et al NEJM 352:1977, 2005

PIVOT TRIAL: Observation vs. Radical Prostatectomy

• 731 men, randomized, 1994-2002• Mean age 67; Intention to treat analysis• Median followup: 10 years• All cause MR: 47% vs. 49.9%• CaP MR: 5.8% vs. 8.4% (p = 0.09)• ↓ all cause MR if PSA >10 and

possibly intermediate/high risk CaP

Wilt,TJ et al. NEJM 2012; 367:203

PIVOT TRIAL: Observation vs. Radical Prostatectomy

• Original goal 2000 pts

• Median age older (67 y/o); only 50% T1c

• VA population with ↑ comorbidities

• 25% of pts. for RRP did not undergo Rx

• 10% of pts. for obs. underwent RRP

• Bone mets in obs. - 10% vs. 4.7%

Wilt,TJ et al. NEJM 2012; 367:203

Open Radical Prostatectomy

• 2 ½ hour operation

• 2 day hospitalization

• Catheter x 1 week

• Recovery 3-4 weeks

• Palpation of prostate

http://www.orlive.com/brighamandwomens/videos

Robotic Radical Prostatectomy

• 2-3 hour operation

• 1 day hospitalization

• Catheter x 1 week

• Recovery 2-3 weeks

• Long learning curve (minimum 300)

• No palpation of prostate

Radical Prostatectomy

Advantages• Definitive therapy to

remove primary tumor• Stage dependent• Allows for pathological

staging • Better prognosis

determination• Nerve sparing• Psychological impact

Disadvantages• Major inpatient surgery

– Bleeding during surgery

• Incontinence• Persistent erectile

dysfunction• Bowel complications• Anastomotic stricture• Recovery period – loss of

human capital

Eastham JA, Scardino PT. Campbell’s Urology. 8th ed. Philadelphia, Pa: WB Saunders; 2002:3080,3091,3126.

External Beam Radiation Therapy (EBRT)

3D ConformalAdvantages• Efficacy equal to

prostatectomy at 5 years• Outpatient procedure• More precise treatment

target - less side effects than nonconformal

• Painless procedure • Allows escalation of RT

dose to 81 Gy• No loss in human capital

Disadvantages• Acute/chronic bowel

complications• Incontinence• Persistent erectile

dysfunction • Daily treatments for

7-8 weeks

D’Amico, AV, et al. Campbell’s Urology. 8th ed. Philadelphia, Pa: WB Saunders; 2002:3152.Zelefsky MJ, et al. J Urol. 2001;166:876-881.

Intensity Modulated RT (IMRT)

• Inverse treatment planning• Computer controlled RT intensity• Mathematical optimization technique utilized• Enables further delivery of minimal and maximal

dose RT vs 3-D EBRT• Less rectal complications than 3-D and conventional

EBRT• Allows escalation of the RT dose to 86.4 Gy• Limited availability

D’Amico, AV, et al. Campbell’s Urology. 8th ed. Philadelphia, Pa: WB Saunders; 2002:3155.Zelefsky MJ, et al. J of Urol. 2001;166:876-881.

Brachytherapy

Advantages • Efficacy approaching that

of EBRT or surgery (short term)

• Procedure completed in one session

• Outpatient procedure• Delivers higher doses

radiation over shorter period of time

Disadvantages • Urinary voiding symptoms• Rectal discomfort• Edema • Persistent erectile dysfunction• Migration of seeds • Variability of duration of action• Epidural or general anesthesia• Unknown long-term effectiveness

(10-year effectiveness)

D’Amico, AV, et al. Campbell’s Urology. 8th ed. Philadelphia, Pa: WB Saunders; 2002:3158.Grimm PD, et al. Int J Radiat Oncol Biol Phys. 2001;51:31-40.Beyer DC, et al. Radiother Oncol. 2000;57:263-267.Blasko JC, et al. Radiother Oncol. 2000;57;273-278.

MGT. of Localized CaP

• Optimal Rx of local disease controversial• Radical prostatectomy is the most proven

method for long term survival• Quality of life is an important consideration• Further improvements in survival depend on

development of effective adjuvant Rx