SRO Tutorial: Prostate Cancer

Treatment Options May 7th, 2010

Daniel M. Aebersold

Klinik und Poliklinik für Radio-Onkologie Universität Bern, Inselspital

„Is cure necessary in those in whom it may be possible, and is cure possible in

those in whom it is necessary?“

W.F. Whitmore Jr.

Urol Clin North Am 1990; 17: 689

Watchful waiting vs. Prostatectomy

Bill-Axelson 2005 NEJM

Watchful waiting vs. Prostatectomy

Bill-Axelson 2005 NEJM

100

0

20

0 15

Radical radiation for localized prostate cancer

5 10

local control (n=1271)

60

40

80

local failure (n=198)

met

asta

sis-

free

surv

ival

(%)

years

J.J. Coen, W.U. Shipley et al., J Clin Oncol 20:3199-3205, 2002

p<0.0001

Distant metastasis free survival by local disease status.

10

0

2

0-3 9-12

Radical radiation for localized prostate cancer

Hazard rate of distant metastasis by local disease status

3-6 6-9

6

4

8

haza

rd ra

te o

f DM

(%/y

r)

years

J.J. Coen, W.U. Shipley et al., J Clin Oncol 20:3199-3205, 2002

12-15

local control local failure

Korrelation LC mit DM?

The Decision

•  Discussion between patient and doctor •  Thoroughly discuss various options

available •  Thoroughly discuss the procedure •  Patient should be fully aware of risks

and potential complications

Considerations Prior to Treatment

•  Patient’s general medical condition and age •  Tumor Grade (Gleason Score) and serum PSA •  Disease Stage and the likelihood of the cancer

being confined to the prostate gland and thus potentially curable

•  Estimation of outcome compared to other treatments

•  Side effects from various treatments

Goals of Treatment (In Order of Priority)

1.  Cancer Control

2.  Preservation of Urinary Control (Continence)

3.  Preservation of Sexual Function (Potency)

Therapy decision is dependent on:

1. Live expectancy >5y or <5y 2. Clinical stage 3. PSA 4. Gleason-Score

UROLOGY 2003; 61: 14-24

www.nccn.com

Asymptomatic, Gleason ≤ 7 ⇒ watchful waiting (ww)

High risk factors (impending hydronephrosis or metastasis): bulky T3-4, Gleason 8-9 ⇒ TAB oder palliative RT

Why Wait? •  PSA and DRE can detect prostate cancer at a

very early stage •  Average doubling time of a prostate tumor is

quite slow (2-4 years) •  Immediate radical therapy may constitute over-

treatment and an introduce unnecessary urinary and potency risks

•  May be appropriate if the patient is elderly and/or in poor health, and will live out their life spans without the cancer causing problems

•  May also be appropriate for a younger patient who is willing to be vigilant and accept the risk of the cancer spreading

Primary Androgen Ablation

•  Nobel Prize •  Testosterone necessary for

the growth and development of prostate cancer

•  Removal of testosterone results in apoptosis of stromal and epithelial cells

Primary Androgen Ablation

•  Palliative

•  An active decision not to pursue curative therapy

•  If a man lives long enough he will die from prostate cancer

Results of Androgen Removal

•  Impotence •  Loss of sexual desire (libido) •  Hot flashes •  Weight gain, Increased appetite •  Fatigue •  Reduced brain function •  Loss of muscle and bone mass •  Some cardiovascular risks •  Hot flashes •  Gynecomastia and breast tenderness •  Bone loss

  low risk of recurrence

  intermediate risk of recurrence

  high risk of recurrence

  very high risk of recurrence

Definition: T1-T2a and PSA ≤ 10 and Gleason 2-6

Therapy: LE < 10y ww or RT LE 10-20y ww, RT or OP LE > 20y RT or OP RT: 3dRT, IMRT, Brachytherapy (HDR/LDR)

Definition: T2b –T2c or Gleason 7 or PSA 10-20

Therapy: LE < 10y ww, RT oder OP LE > 10y RT oder OP

No brachytherapy only

Definition: T3a or

Gleason 8-10 or

PSA > 20

Therapy: LE <5y ww or TAB LE > 5y TAB (2-3y) + RT RT + 6m (TAB) with only 1 risk actor (OP)

Definition: T3b – T4 ⇒ TAB +/- RT

any T, N1 ⇒ TAB +/- RT

any T, any N, M1 ⇒ TAB

Hormone-Refractory Prostate Cancer (HRPC) = Castration Resistent PC

•  Despite initial response rates of 80-90%, nearly all men with advanced prostate cancer develop hormone-resistant prostate cancer after 18-24 months

•  These “hormone-refractory” (HR) prostate cancer cells can grow in the absence of androgens

•  The behavior of HR prostate cancers differ widely between patients