Protocols for Advanced Prostate Cancer and/or Local Failure After

Radical Prostatectomy

Isaac Powell, MD

ARS

???

Case Presentation

• Local spread outside of the prostate gland with or without positive surgical margins after radical prostatectomy

• Detectable PSA or rising PSA after surgery

Post-op advanced stage

Prostate Cancer-Specific Survival

D'Amico A, et al. Prostate cancer mortality based on PSADT after

surgery. JNCI 2003

Prostate cancer specific mortality

<2 mo.

<3

<4

<6

<12

PSADT

Per

cent

Dea

d of

Pro

stat

e C

ance

r

A RANDOMIZED, OPEN LABEL, MULTICENTER, PHASE III, 2-ARM STUDY OF

ANDROGEN DEPRIVATION WITH LEUPROLIDE, +/- DOCETAXEL FOR

CLINICALLY ASYMPTOMATIC PROSTATE CANCER SUBJECTS WITH A RISING PSA

FOLLOWING DEFINITIVE LOCAL THERAPY

Schematic of Trial Design

• Rising PSA following radical prostatectomy

• PSA doubling time of <9 months

• Minimum PSA of 1• Testosterone >100ng/ml

RA

ND

OM

IZE

•Docetaxel 75 mg/m2 q 3 weeks x 10 cycles

•GnRH agonist x 18 months

•Bicalutamide x 4 weeks

•GnRH agonist x 18 months•Bicalutamide x 4 weeks

Arm A

Arm B

The hypothesis of the study is that Progression Free Servival probability will increase from 50% to 65% a minimum 36 months following randomization.

Additional Eligibility

• Subjects in this group may have no radiographic findings that are clinically suspicious for metastatic disease.

• Salvage Radiotherapy is allowable and encouraged where appropriate (for example, biochemical recurrence with a positive margin)

Version 3.0 / March 24, 2008 Amendment #2

Primary Objective

• Progression Free Survival within the period of 18 months of therapy and at least 18 months follow-up.

• Progression Free Survival is determined as the time from randomization to:– the first documentation of detectable PSA or – radiographic progression or – to death

Secondary Objectives

• To evaluate cancer specific survival

• To compare overall survival between the 2 treatment groups

• Molecular correlates with clinical outcomes– Tissue blocks– Serum/DNA

Radiotherapy Protocol After Surgery (closed)

Adjuvant Radiotherapy for Pathological T3N0M0 Prostate Cancer Significantly Reduces Risk of Metastases and Improves Survival: Long-Term Followup of a Randomized Clinical Trial

Ian M. Thompson,*,† Catherine M. Tangen, Jorge Paradelo, M. Scott Lucia,Gary Miller,‡ Dean Troyer, Edward Messing, Jeffrey Forman, Joseph Chin,Gregory Swanson, Edith Canby-Hagino and E. David Crawford

Materials and Methods: A total of 431 men with pT3N0M0 prostate cancer wererandomized to 60 to 64 Gy adjuvant radiotherapy or observation. The primarystudy end point was metastasis-free survival.

Figure 1 Metastasis-free survival by treatment arm

Conclusions: Adjuvant radiotherapy after radical prostatectomy for a man withpT3N0M0 prostate cancer significantly reduces the risk of metastasis and increasessurvival.

Lymph node metastasis

Conclusion

• Locally advanced prostate cancer plus early aggressive combination therapy equal long term survival and possibly “cure”.