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Giorgio Arcangeli Highlights in the Management of Urogenital Cancer Rome May 9-10, 2008 Radiation Therapy is the best treatment approach for localized.

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Presentation on theme: "Giorgio Arcangeli Highlights in the Management of Urogenital Cancer Rome May 9-10, 2008 Radiation Therapy is the best treatment approach for localized."— Presentation transcript:

1 Giorgio Arcangeli Highlights in the Management of Urogenital Cancer Rome May 9-10, 2008 Radiation Therapy is the best treatment approach for localized prostate cancer Radiation Therapy is the best treatment approach for localized prostate cancer

2 CARCINOMA OF THE PROSTATE risk to treat scarcely aggressive indolent tumors risk to treat scarcely aggressive indolent tumors multiple therapeutic options multiple therapeutic options High probability of cure in localized tumors High probability of cure in localized tumors

3 CRITERIA FOR TREATMENT CHOICE  TUMOR RELATED (Stage - G.S. - PSA)  PATIENT RELATED (age - P.S.)  TREATMENT RELATED (Acute and late side effects, QOL)

4 Clinical Staging of prostate cancer

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8 SISTEMA DI GLEASON (1974) SISTEMA DI GLEASON MODIFICATO (ISUP 2005)

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11 CARCINOMA OF THE PROSTATA Definitive treatment options in localized tumors HIGH DOSE RADIOTHERAPY± ANDROGEN DEPRIV. RADICAL PROSTATECTOMY RADICAL PROSTATECTOMY

12 AGE < 70 years (Harlan: J Clin Oncol, 1995) YEARS OF DIAGNOSIS CARCINOMA OF THE PROSTATE

13 YEARS OF DIAGNOSI (Harlan: J Clin Oncol, 1995) AGE > 70 anni CARCINOMA OF THE PROSTATE

14 A Multi-institutional* Pooled Analysis of Radiation Therapy For Clinically Localized Prostate Cancer (Shipley, JAMA 281:1598, 1999) * Fox Chase; Mass General; Michigan University; Washington University; EVMS; Stanford

15 ACR Patterns of Care Study : Risk of Grade 3-4 Complications by Radiation Dose in Carcinoma of the Prostate Dose# Patients% Complications <70 Gy 428 3.5% >70 Gy 174 6.9% p = 0.03 Modified from Leibel SA, Hanks GE, Kramer S. IJROBP, 10, 401, 1984

16 12010080604020 0 40 60 80 100 Prescription Dose Probability (%) Shifting The Organ Toxicity Curve by Decreasing the Irradiated Volume Tumor Control Organ Toxicity

17 Multileaf Collimator for Conformal or Intensity Modulater Radiation Therapy

18 Dynamic Multileaf ( “Sliding window”) le lamelle si muovono in modo continuo ed unidirezionale durante l’erogazione, sempre da sinistra verso destra, fino ad una velocità di 2.5 cm/s; ogni lamella si sposta a velocità diversa dalle altre, ricongiungendosi alla lamella opposta nella posizione finale; l’erogazione è continua durante il movimento delle lamelle. Fluence Matrix

19 Why IMRT ??? Creation of concave or convex isodose surfaces with sharp dose gradients Higher dose to target volume Specific sparing of sensitive volumes (organs at risk) within complex treatment geometries With IMRT dose distribution can be shaped to the target to spare Organs at Risk Beam Profile #1 1 Beam Profile # 2 Beam Profile #3 Dose Intensity PTV RORO RO PTV 3-field IMRT Prescribed Dose (typical distribution) 3-field RT

20 Isodose comparison betwen CRT or IMRT 20-30% 40-50% 60-70% 80-90% 90-100% >100% 20-30% 40-50% 60-70% 80-90% 90-100% >100% Dose prescription: 80 Gy to isocentre, 2 Gy per fractions, 5 fr/week 6 FIELDS-3DCRT 5 FIELDS-IMRT bladdder 6 fields-3DCRT 5 fields-IMRT PTV rectum

21 Percent Grade 2 Rectal Bleeding 01224364860728496108 Time (months) 0 5 10 15 20 6480 cGy (96) 7020 cGy (268) 7560 cGy (446) 8100 cGy (61) Zelefsky 1999

22 Percent ≥ Grade 2 GI Toxicity 01224364860728496 Months 5 10 15 20 p< 0.001 81 Gy IMRT (171) 81 Gy Conventional 3D-CRT (61) 0 Zelefsky 2001

23 Dose escalation with External Beam Radiation Therapy

24 Biochemical Failure-Free Zietman AL, JAMA 2005 All Pts. Intermediate to high risk Low risk 70.2 Gy vs 79.2 Gy

25 Peeters STH et al. JCO 2006

26 Conventional vs. High dose 3D-CRT in pts with prostate cancer receiving 3-6 mos NCADT Randomized phase III study (MRC RT01) 74 Gy 64 Gy HR=0.67(0.53-0.85) P=0.0007 Dearnaley, Lancet Oncol 2007

27 External Beam Radiation Therapy Vs Radical Prostatectomy

28 bNed for surgically and radiation-managed patients stratified into risk groups low risk intermediaterisk high risk D’Amico A, IJROBP 1997

29 bRFS in pts with favorable tumors (T1-T2A, bGS< 6, iPSA< 10 ng/ml) Kupelian PA, JCO 2002

30 bRFS in pts with unfavorable tumors (T2b-T2c, bGS> 6, iPSA>10 ng/ml) Kupelian PA, JCO 2002

31 Akakura K, Jpn J Clin Oncol 2006 bNEDOS P=0.25 P=0.30 RP: 46 pts – EBRT (60-70 Gy): 49 pts (2 month neoadjuv DES 300mg and adjuv LHRH until progress)

32 Characteristics of Pts with high risk prostate cancer Variable RP EBRT p-value Median Age 65.5 75.0 <0.001 bGS < 6 29 (24%) 17 (10%) 7 82 (67%) 105 (65%) <0.001 > 8 11 (9%) 40 (25%) cT-Stage T2c 8 (7%) 21 (9%) iPSA <10 2 (1%) 44 (27%) 11-20 57 (47%) 55 (34%) <0.001 >20 63 (52%) 63 (39%) Median FU 30.5 mos 30.7 mos 0.56

33 EAU Guidlines for follow-up after treatment with curative intent After RP a serum PSA level > 0.2 can be associated with residual or recurrent disease (grade B recommendation) After EBRT a rising PSA level 2.0 ng/ml above the nadir value, rather than a specific threshold value, is the most reliable sign of persistent or recurrent disease (grade B recommendation) Both a palpable nodule and rising PSA level can be signs of local disease recurrence (grade B recommendation) Eur Urology 2008

34 p=n.s. (238 pts.) (46 pts.) (238 pts.) (104 pts.) (180 pts.) (46 pts.) FFBF in high risk prostate tumors according to different scores of clinical prognostic factors IRE Apr 2008 bGS iPSA cT-stage

35 (123 pts.) (159 pts.) FFBF as a function of Age in pts with high risk prostate cancer treated with RP or EBRT IRE Apr 2008

36 p = 0,0012 (162 pts.) (122 pts.) FFBF after RP or EBRT in pts with high risk prostate cancer IRE Apr 2008

37 RP p=n.s.= 0.06p=n.s EBRT p=0.005 p=n.s. FFBF according to bGS ± 8 and iPSA ± 20 ng for RP and EBRT (11 pts) (111 pts) (40 pts) (122 pts) (63 pts) (59 pts) (63 pts) (99 pts)

38 p = 0.0161 FFBF of Pts with worst prognosis according to the treatment received IRE Apr 2008

39 FFBF after RP or EBRT using 0.5 ng PSA threshold for bRelapse definition All PTS Very high risk PTS p=ns (162 pts) (122 pts) p=ns

40 (152pts.) ( 10pts.) p= 0.001 FFBF according to nPSA in Pts treated with EBRT IRE Apr 2008

41 p=0.62 p=0.06 p=0.0001 (162 pts.) (83pts.) (39 pts.) FFBF of Pts treated with EBRT, RP only or RP + Adjuvant Treatment IRE Apr 2008

42 p=n.s. p=0.008 p=n.s. FFBF according to different scores of pathologic factors (88 pts) (23 pts) (17 pts) (96 pts) (25 pts) (71 pts) (8 pts) (103 pts)

43 Univariate analysis of RP patient Variable 3-yr FFBF rate p-value bGS (≥8 vs <8) 72% vs 77% 0.74 cT (>T2c vs 20 vs < 20) 68% vs 81% 0.06 SM + vs SM - 79% vs 72% 0.73 pGS (>8 vs <8) 53% vs 81% 0.008 pN + vs pN - 60% vs 73% 0.53 pT (>T2c vs { "@context": "http://schema.org", "@type": "ImageObject", "contentUrl": "http://images.slideplayer.com/14/4383638/slides/slide_43.jpg", "name": "Univariate analysis of RP patient Variable 3-yr FFBF rate p-value bGS (≥8 vs <8) 72% vs 77% 0.74 cT (>T2c vs 20 vs < 20) 68% vs 81% 0.06 SM + vs SM - 79% vs 72% 0.73 pGS (>8 vs <8) 53% vs 81% 0.008 pN + vs pN - 60% vs 73% 0.53 pT (>T2c vs T2c vs 20 vs < 20) 68% vs 81% 0.06 SM + vs SM - 79% vs 72% 0.73 pGS (>8 vs <8) 53% vs 81% 0.008 pN + vs pN - 60% vs 73% 0.53 pT (>T2c vs

44 Univariate analysis of EBRT patient Variable 3-yr FFBF rate p-value bGS (>8 vs <8) 77% vs 93% 0.005 cT (>T2c vs 20 vs < 20) 86% vs 91% 0.26 nPSA (>0.5 vs <0.5) 40% vs 94% 0. 001 Fractionation (standard vs hypo) 76% vs 96% 0.06

45 Univariate analysis of all patients Variable 3-yr FFBF rate p-value bGS (> 8 vs < 8) 73% vs 85% 0.17 cT (>T2c vs 20 vs < 20) 76% vs 81% 0.01 Age (>70 vs <70) 84% vs 80% 0. 61 Treatment (RP vs EBRT) 80% vs 92% 0.001

46 Summary of Multivariate Analysis Group Variable p-value RP pGS ( 7) 0.04 EBRT nPSA (continuous) 0.0002 All PTS iPSA (continuous) 0.01 Treatment (RP vs EBRT) 0.007

47 Rectal and urinary late toxicity

48 Incidence of grade >2 late toxicity rectal urinary convent hypo IRE, Oct 2007

49 Radiation Proctitis Related Factors Radiation related factors Total dose Dose per fraction Dose/volume relationship PTV size RT technique N° of RT fields Rectal motion Patient related factors Previous history of proctitis Previous abdominal surgery Cardiovascular disease Arterial hypertension Peripheral vascular disease Diabetes Hemorrhoids Prostate size Long term ADT

50 9 Non confluent multiple Telangectasia

51 Freedom from rectal toxicity as a function of rectal volume receiving > 70 Gy (V 70 ) Pollack IJROBP 2002

52 Disfunzione erettile

53 Sexual potency preservation –Radiotherapy:73% –Radiotherapy (high doses):61% –Radiotherapy + neoadiuv ADT:79% –Radioterapia + adiuvant ADT: 0% Pilepich 1999, D’Amico&Zelefsky ASTRO2004 Radiation mediated impotence is multifactorial. Of pts. evaluated for impotence, 63% had arteriogenetic dysfunction, 31% cavernosal dysfunction, and only 3% had a neurogenic impotence

54 Merrick GS ASTRO 2004

55 Merrick GS ASTRO 2004

56 Merrick GS ASTRO 2004

57 Tsai HK, JNCI 2007 EBRT, age≥65 yrEBRT, age<65 yr RP, age<65 yr RP, age≥65 yr

58 Quality of life -Prospective evaluation -Patient/Physician evaluation -Validated instruments

59 Litwin Cancer 007 Brachytherapy EBRT RP Brachytherapy EBRT RP Actuarial analysis of the subjects returned to baseline HRQOL scores

60 Litwin Cancer 2007 All Pts Pts initially potent Actuarial analysis of the subjects returned to baseline sexual scores Brachytherapy EBRT RP Brachytherapy EBRT RP nerve-sparing RP non nerve-spar

61 Grazie per la Vostra Attenzione! Attenzione! Ringrazio: Pr. M Gallucci, Dr. P De Carli, Dr. R Papalia (Div. Urologia), Dr. L Strigari, Dr V Landoni, Pr. M Benassi (Lab Fisica Medica) e i miei collaboratori della SC Radioterapia: Dr. B Saracino, Dr. MG Petrongari M, Dr. S Gomellini, Dr. S Arcangeli.


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