Therapy in Prostate Cancer: Cure or Regression

Transcription

1 Therapy in Prostate Cancer: Cure or Regression F. Di Silverio Department of Urologia U Bracci University La Sapienza Rome

2 Objectives and classification of the results obtained from therapies in oncology Cure Complete Remission Partial Remission Stable Disease Progression (C.R.) (P.R.) (S.D.) (Pr)

3 To CURE is possible when : it is present a marker for biological activity of the tumor Prostate cancer Testis cancer = PSA = α feto, βhgc

4 Objectives and classification of the results obtained from therapies in oncology urgical Radicality = Pathology + iological Radicality = undetectable PSA To CURE

5 Response to therapy is influenced by a crucial variable TIME (t)

6 Variable TIME (t) in results of therapies in oncology TIME (t) ure indefinite mplete Remission artial Remission able Disease rogression (C.R.) (P.R.) (S.D.) (Pr) > 10 yrs 5-10 yrs months months

7 Variable TIME (t) in results of therapies for prostate carcinoma yrs 14 CURE t RRP RTE HT Chemio

8 Variable TIME (t) in results of therapies for prostate carcinoma Variable TIME (t) is related to: Time to diagnosis Early Deferred

9 Variable Variable TIME (t) in results of therapies for prostate carcinoma Early diagnosis Deferred Diagnosis Stage localized advanced Grading Gleason </= 7(3+4) >/= 7 (4+3) DNA diploid aneuploid AR expressed no expressed

10 Variable TIME (t) in results of therapies for prostate carcinoma QUESTION When and from which therapy we can obtain CURE?

11 hen and from which therapy we can tain CURE? ANSWER Radical Prostatectomy if: o Localized stage o Gleason </= 7(3+4) o PSA < 10 ng/ml

12 Why we can not obtain CURE after diotherapy but only Complete Remission ANSWER Only C.R. because: o prostate gland remains o no pathological stage (pt,pn) o prolonged half-time for PSA o positivity to tissue PSA also after 5 years

13 aluation of limits of therapies for ostate carcinoma ME (t) = lenght of therapeutic efficacy QUESTION an we increase TIME (t) of therapeutic fficacy?

14 an we increase TIME of therapeutic efficacy Therapy Modality RRP (high risk cases) Hormone-therapy RT Hormone-therapy HT HRPC therapy Early, not deferred Choice of the drug Sequenziality Intermittence Estrogens

15 n we increase TIME of therapeutic efficacy of RR Progression-free survival: locally advanced radical prostatectomy portion gressing Bicalutamide ( Casodex ) 150 mg Placebo Time to progression (years).71; 95% CI 0.57, 0.89; p= lutamide ( Casodex ) 150 mg events = 136 (15.6%) ebo events = 170 (20.0%) EPC Stud

16 an we increase TIME of therapeutic efficacy Radiotherapy RT RT RT + HT Local control 10 yrs 56% 70% Survival 10 yrs 28% 46%

17 an we increase TIME of therapeutic efficacy of RT Progression-free survival: locally advanced radiotherapy portion 1.0 gressing Bicalutamide ( Casodex ) 150 mg Placebo Time to progression (years).58; 95% CI 0.41, 0.84; p= lutamide ( Casodex ) 150 mg events = 54 (33.5%) ebo events = 70 (48.6%) EPC Stud

18 an we increase TIME of therapeutic efficacy ormone- Therapy choice of the drug sequentiality modality of administration

19 T can reduce androgen sensibility of PC Influence on TIME (t) of response Throught selection of androgen-independent cells cellular re-differentiation hyperactivation Neuroendocrine system (N

20 Choice of the drug during HT imary use of antiandrogen aintenance of AR

21 Locally advanced PC Bicalutamide: KW= p= LH-RH analogue KW= p< LHRH-analogu Bicalutamid 30 baseline Mon F. Di Silverio, A. Sciarra EAU 2003, Urology 2004

22 A l Metastatic PC IAD: F=3.206; p=0.124 Continuous: F=17.233;p=0.006 Continuous IAD 50 aseline Months F. Di Silverio, A. Sci

23 o Conclusions but a possible Future croenvironment in which tumor cells are located a potential effect in reducing anti tumor effect therapies Microenvironmen ls

24 icroenvironment can influence TIME (t) in PC Role of Microenvironment in the induction, progression and response to therapy for PC Nature :

25 ole of Microenvironment on TIME (t) in PC Nitric Oxide N.O. promotes angiogenesis N.O. promotes tumor growth Jenikins DC et al. Proc Natl Med Sci 1995;92:

26 Cyclo-Oxigenase

27 ole of Microenvironment on TIME (t) in PC COX-2 promotes angiogenesis promotes tumor growth increases resistance to therapies Jenikins DC et al. Proc Natl Med Sci 1995;92:

28 hen to act on Microenvironment so to fluence TIME (t) in PC se of anti - COX-2 in the prevention of PC Atrophy, HGPIN) n association with hormone - therapy n off phases of IAD revention of HRPC

29 Conclusions The best knowledge of the natural history and of microenvironment consent to obtain a better prognosis, quality of life and survival To delay the development of HRPC represents the primary target in the management of HT and the patient with prostate carcinoma