Brachiterapia con impianto permanente nel trattamento del carcinoma prostatico localizzato: l esperienza di Trento

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1 Brachiterapia con impianto permanente nel trattamento del carcinoma prostatico localizzato: l esperienza di Trento Maggio 2000 dicembre/2005: 254 pazienti Età mediana 66 anni (range 50-77) Associazione con OT: 114 e con RTE: 15 F-U U mediano 40 mesi (range( 18-80) 80) SIUrO XVII Modena novembre 2007 nefropatia altre comorbidità no cardio/arterio-patia n % ipertensione diabete 23 9 altro tumore 13 5 altro tumore ipertensione altre nefropatia 3 1 diabete no tot cardio/arteriopatia 1

2 I-PSS 170 LOW RISK PATIENTS (T1c-T2a, GS <7, ipsa<10 ng/ml) 74 INTERMEDIATE RISK PATIENTS (T2b-c or GS 7 or ipsa10-20 ng/ml) 10 HIGH RISK PATIENTS (T2b-c and/or GS >7 and/or ipsa10-20 ng/ml) 4% 29% Low Risk Intermediate Risk High Risk 67% 2

3 145 Gy 145 Gy 145 Gy TRUS prep-plan intraop Pre-plan prostata retto uretra 3

4 DVH constraints (pre-planning) Prostata: V100 > 98%. Uretra: Dmax < 150%. Retto: V100 < 0.3 cc. 4

5 impianto con guida ecografica 5

6 Post-plan 100 Gy 145 Gy 210 Gy TAC postplanning (a 1 mese) uretra prostata retto 6

7 D90 V pazienti DVH prostata postplanning a 1 mese 92% a 4 anni (DSS 100%) 7

8 (nadir + 2) 97% a 4 anni Conclusioni È stato possibile implementare e adottare la metodica brachiterapica in un contesto multidisciplinare Tale contesto garantisce una selezione corretta dei pazienti ed una adeguata informazione durante il processo di counseling L unione di differenti competenze (urologo, fisico, radioterapista, oncologo) ha consentito una ottimale qualità degli impianti Selezione corretta ed impianto adeguato sono alla base dei buoni risultati preliminari ottenuti e rappresentano una garanzia per il risultato a più lungo termine 8

9 Risultati a lungo termine N pts. median f.u. bned Grimm (Seattle) m. 85% 15a Ragde (Seattle) m. 77% 13a. Critz (Georgia) m. 83% 10a. Beyer (Arizona) m. 65% 10a. Potters (MSKCC) m. 81% 12a. Merrick (SCC) m. 93% 8a. Stone (Mt. Sinai) m. 87% 10a pz *888 Prostatectomia Radicale *218 Brachiterapia ± ADT *766 RT FasciEsterni (casistica retrospettiva) RR di ricaduta biochimica a 5 anni rispetto a PR Low-risk Radioterapia: 1.1 (C.I.95% ) Brachiterapia: 1.1 (C.I.95% ) BT + ADT: 0.5 (C.I.95% ) High intermediate-risk intermediate-risk BT: 3.1 (C.I.95% ) high-risk BT: 3.0 (C.I.95% ) 9

10 Gruppi di rischio e bned low intermediate high Stone et al. 10 yrs 94% 89% 78% Grimm et al. 15 yrs 86% 85% --- Potters et al. 12 yrs 91% 80% 76% Critz et al. 10 yrs 93% 80% 61% Merrick et al. 8 yrs 97% 97% 84% 2693 pt in 11 inst median fu 63 m 10

11 six centers -3,928 patients LR IR HR RP vs BT vs BT+EBRT bned vs EBRT >72 Gy vs EBRT <72 Gy *Kupelian PA et al, IJROBP 58: 25-33: Cleveland Clinic/MSKCC Treatment Comparisons BT (mono) BT+EBRT 2991 patients fu 56 months EBRT>72 Gy RP Time (months) 77% 83% 51% EBRT<72 Gy 11

12 Survival of Men With Clinically Localized Prostate Cancer Treated With Prostatectomy, Brachytherapy, or No Definitive Treatment J D Tward et al; Cancer 107: 2392, 2006 SEER-Medicare database, men RP 34758, BT 6637, WW median fu 46 m For men seeking a definitive treatment, both younger and older men should be counseled that either surgery or brachytherapy is appropriate COMPLICANZE 12

13 Advantages of permanent prostate brachytherapy ASTRO GS Merrick, JC Blasko. Minimally invasive procedure Rapid return to normal activities Documented long-termbiochemical results Effective for all risk groups Favorable morbidity profile Modalità di RT e dose Gy Conventional Conformal IMRT HDR Seeds* *RBE dose 13

14 Comparing the time to resolution of spectroscopic abnormalities (RSA) in low-risk EFFETTI COLLATERALI.- DATA REPORTING Selezione (fattori paziente correlati) Trattamento: tipo e modalità (fattori terapia correlati) End point rilevato (function, bother, analitico) Definizione dell end point Modalità del rilievo (records medici, self reporting, prospettica) Strumento di misura (sistema di gradazione -sensibilità) 14

15 Sequele urinarie ritenzione acuta TURP recupero IPSS basale stenosi uretrale tardiva 2-22% 1-5% 6-12 mesi 5-10% UROLOGY 70: , patients 21 required catheterization (3.2%) ROC curves 15

16 IJROBP 64: 825, 2006 IJROBP 52: 453,

17 IJROBP 32: 465, 1995 Urethral dose < 400 Gy IJROBP 62: 981, 2005 Withstrictadherenceto urethral-sparingtechniques, detailedurethral dosimetrydidnotsubstantiallyimprove the abilityto predicturinary morbidity Numberof patientsreporting eitheran increase or decreaseof one to fivepoints in theirurinaryfrequency assessment from beforeimplantationto lastfollow-up evaluation(mean, 39 months); 78 patientsreported no change 17

18 IJROBP 48: 119, 2000 serious rectalinjuryis rare 213 pazienti, follow-up mediano 22 mesi. aumento della frequenza e delle perdite di muco con picco a 1 mese (generalmente G1), e successivo ritorno alla base-line. maggior sensibilità del sistema R-FAS R rispetto ai criteri RTOG relativamente ai gradi bassi. non differenza significativa col supplemento di RT esterna. importanza di una valutazione prospettica. Bracytherapy2: 147,

19 IJROBP 50: 335, 2001 rectalvolume thresholdsassociated with 5% risk of Grade 2 proctitisat 5 years. JU 172: 515, 2004 Of the 1,584 patientsincludedin the sample1,276 underwent RP, 99 received XRT and 209 received BT - 2y FU period Bowel function Bowel bother 19

20 IJROBP 57: 42, pazienti. R-FAS FU mediano 66 m IJROBP 54: 1063, 2002 Methods: A comprehensive literature review and subsequent meta- analysis (54 studies; median agebrachytherapy 68, prostatectomy 61-63) Results: The predicted probability of maintaining erectile function after brachytherapy was 0.76, after brachytherapy plus EBRT 0.60, after EBRT 0.55, after nerve-sparingradical prostatectomy 0.34, after standard radical prostatectomy 0.25, and after cryotherapy0.13. No brachytherapy studies hada follow-up of >2 years. Whenthe probabilities were adjusted forage, the spread was greater 20

21 bande neurovascolarie via di diffusione K KENNETH CHAO: IJROBP 65: 999, Gy 210 Gy I125 TAC postplanning 21

22 IJROBP 53: 928, 2002 closer attentionto penile erectile tissue doses should lead to improved externalbeamradiationand brachytherapy delivery Brachiterapia I125 TC postplanning 15 Gy 10 Gy 22

23 Post-plan 100 Gy 145 Gy 210 Gy we believe that the rationale for sparing the penile bulb is not sufficientlysupportedbythe current literature 23

24 It isessentialthattoxicitydata becollected and reportedin a uniform fashion. Thus, the critical organsfor toxicitymustbedefined and the correspondingdosimetryreportedin a standard fashion such thatguidelinescan beestablishedin the future based on data from a crosssection of centers Brachytherapy 4: 186, 2005 Cumulative rectal dose-volume histogram for 3 methodsof contouringthe rectum Post-plan 100 Gy 145 Gy 210 Gy 24

25 uretra prostata retto prostata uretra retto 25

26 Post-plan 145 Gy 210 Gy Patients and Methods Weanalyzed claims formedicare-enrolled men (SEER) Results There were 5,621 men who hadbrachytherapy with at least 2 years of follow-up. A complication diagnosis or invasive procedure occurred in 54.5% of men within2 years, with14.1% undergoing an invasive procedure. Conclusion Morbidity after prostate brachytherapy was common, though invasive procedures were required infrequently. JCO 24: 5298,

27 Trento pazienti IJROBP 66: 31,

28 80 benessere fisico 90 benessere psicologico ,5 87,3 71,6 87, ,4 72,6 72, ,5 82,6 82,5 84, PRE POST 1 y 2 y autonomia fisica 3 y 80 PRE p = NS 80 POST 1 y 2 y vita di relazione 77,4 3 y 95 91, , , , , ,6 88,4 87, PRE POST 1 y 2 y 3 y PRE POST 1 y 2 y 3 y funzione urinaria 30,5 15 funzione rettale 11, ,6 20, , ,5 7,4 6,6 5,3 PRE POST p < y y 3 y 45,1 44,4 PRE POST funzione sessuale 1 y 2 y 3 y p = NS 40 39, ,5 PRE POST p < y 2 y 3 y 28

29 Funzione urinaria score basale buono score basale scarso 30 26, , , ,1 22, , ,8 5 6, ,8 PRE POST 1 y 2 y 3 y PRE POST 1 y 2 y 3 y J Urol177: 2151, eligiblemen(74 BT) EPIC medianfu y 29

30 of patients withprostate cancertreated with a monotherapy approach we noted betterurinary continence in those who underwent radiation based therapies, and betterbowelfunction and less urinary irritation in those whounderwent surgery. Sexual function was impaired across allmonotherapies, but higherscores were seen in men who selected brachytherapy M S Litwinet al. Cancer109: 2239, eligiblemen(90 BT) UCLA PCI, AUA SI 2 y period 30

31 Qualità di vita dopo trattamento radicale per carcinoma della prostata localizzato: prima analisi dei dati di uno studio prospettico Caffo O et al.- SIUrO XVII.- Modena 2007 BT PR BASALE POST p VALUE BASALE POST p VALUE PHY* NS PSY* NS REL* NS POW* NS URI** SEX** RECT** * valore più alto = migliore risultato funzionale; ** valore più alto = peggiore risultato funzionale JCO 23: , eligiblemen (84 BT) -EPIC26 at a median of 2.6 and 6.2 yearsafter treatment * * Positive change in EPIC score represents an improvement in health status, whilea negative score reflects a decline BT * significantchange controls * extrt PR disease-specifichrqol continues to evolve among men treated withbt 31

32 surgery is most commonly associated with urinary incontinence, EBRT with bowel dysfunction, and IB with irritative voiding symptoms. Patients and providers need to be aware of this when choosing therapy for this common malignancy UO 23: 208, 2005 Zeliadt SB, Cancer 106: 1865, 2006 variations in treatment decisions may be more indicative of differences in the information patients receive rather than truly reflective of underlying patient preferences van Tol-Geerdink JJ, IJROBP 66: 1105, 2006 it should, therefore, be considered to inform patients first and ask partecipation preferences afterwards 32

33 CONCLUSIONI Morbidità perioperatoria virtualmente nulla Complicanze acute costanti ma autolimitanti Outcome a lungo termine soddisfacente ma in evoluzione Qualità dell impianto, trattamenti associati, selezione e informazione AUROlinee 2008 Selezione dei pazienti. La BT con impianto permanente è indicata per le forme a basso rischio. Per il rischio alto - intermedio può essere considerata in associazione con una componente di RTE ± OT: LPE IV, forza della raccomandazione B. I pazienti con sintomi ostruttivi (IPSS > 15, flusso massimo < 15 ml/s), con prostata voluminosa (> 55 cc) o con esiti di TURP non sono candidati ideali per la BT. Una previa OT citoriduttiva può essere considerata per ridurre il volume prostatico: LPE IV, forza della raccomandazione B. 33

34 Carcinogenesi dopo BT studio tipologia composizione riscontro K Moon Cancer 107: 998, 2006 SEER registry BT ± RTE pazienti ( casi) dopo BT il più basso OR di secondo ca SA Gutman IJROBP 66: 48, 2006 casistica retrospettiva pazienti (med fu 4.6 y) non correlazione temporospaziale fra BT e ca colon-retto SL Liauw IJROBP 66: 669, 2006 casistica retrospettiva 348 pazienti (med fu 10.5 y) rischio relativo (osservatiattesi) di ca vescica 2.3 A Nationwide Charge Comparison Of The Principal Treatments For Early Stage Prostate Carcinoma Brandeis J Cancer 89: 1792, Prostatectomia: $ Radioterapia esterna: $ Brachiterapia: $ Cumulative Cost Pattern Comparison of Prostate Cancer Treatments Wilson LS Cancer 109: 518, None compare all contemporary treatment costs, and most focus on initial treatment costs. Because of higher up-front charges for RP surgery, it is not surprising that these first-year costs would show a different pattern than our average annual costs taken over a longer time period, which show RP to cost in the middle range of the different treatment types. 34

35 Brachytherapy Conclusions John C Blasko.- EAU 2004 Higher radiation doses translate into better cure rates Mathematically and biologically, brachytherapy delivers the highest intraprostatic dose 10 year results from multiple institutions confirm excellent and durable cure rates No other treatment can duplicate the simplicity of permanent implants for the successful treatment of early stage prostate cancer Because brachytherapy is both radiological and urological, Urologists should participate in these procedures 35