Dr.Filippo Bertoni, Dr. AlessioBruni. AOU Policlinico di Modena

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1 HIGHLIGHTS IN RADIOTERAPIA Dr.Filippo Bertoni, Dr. AlessioBruni AOU Policlinico di Modena

2 HIGHLIGHTS IN RADIOTERAPIA Dr. Filippo Bertoni, Dr. Alessio Bruni AOU Policlinico di Modena

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4 basso intermedio Alto P.Grimm et al. : BJUI supp: 1,

5 CONCLUSION Modern EBRT is at least as effective as modern Australian surgical and Brachy techniques. All pts. considering treatment for localised PCa should be referred to a radiation oncologist to discuss EBRT as an equivalent option.

6 GIVE ME FIVE! R. Orecchia, BA Jereczek-Fossa, D. Zerini, C. Fodor, A. Cecconi, S. Colangione et al. 1. Out trial: 35 Gy in 5 f ractions (based on the US data, King et al.2013, NCCN 2014 etc.) 1. Trial AIRC-2012: enrollement will start at the end of Courtesy of BA Jereczek-Fossa: Milano 2014

7 PROSTATE CANCER: EBRT / SBRT NCCN v Hypofractionation..

8 14/26 phase I II trials and retrospective studies using SBRT for the treatment of prostate cancer (1472 pts.)

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10 SBRT : Tossicità Tossicità itàacuta (12/14 studi 912 pts) Urinaria G2 : 5 42% G3: 0,5% (4/912 paz) G4: 0% Rettale G2: 0 27% G3: 0% G4: 0% Tossicità tardiva (14/14 studi 1100 pts) Urinaria G2 : 0 29% G3: 0 3,5% (14/1100 paz) G4: 0% Rettale G2: 0 11% G3: 0 5% ( 3/ 1100 paz) G4: 2/1100 paz ( 1 divert.; 1 50 Gy /5fr) T J Tan et al :Journal of Medical Imaging and Radiation Oncology 58 (2014)

11 SBRT: misure di QoL King et al. ( 4 centri, 864 paz; Gy in 4 5 fr; VMAT o CK.; Short course ADT (4 mesi : 14% paz): ) Gli score GU e GI decrescono a 3 mesi per recuperare a 6 mesi (non influenza di ADT e Età) Le funzioni sessuali: decrescono entro 9 mesi e ritornano in maggioranza alla baseline in 12 mesi Friedland d et al : potenza ridotta nel 17% dei pazienti Chen et al : benessere fisico e mentale : sovrapponibile alla baseline Katz. Et al : confronto tra EPIC score (Expanded Prostate cancer Index Composite) Prostatectomia (PR o NSP) vs. SBRT: non differenze per QoL rettali tardivi netto vantaggio della SBRT per GU e funzioni sessuali SBRT: cost-effective analysis Vantaggi clinici e economiciper la SBRT nel carcinom aprostatico cancer. (Costi medi e quality adjusted life years (QALY) (Hodges et al.) ) SBRT $US e 7,9 anni vs. IMRT standard d $ US a 7,9 anni PR Robotica e SBRT $US e 9,9 anni vs. IMRT standard $US e 9,9 anni T J Tan et al :Journal of Medical Imaging and Radiation Oncology 58 (2014)

12 Conclusioni Disponibili solo studi di fase I II con FU limitato. Si attendono risultati a lungo termine. La SBRT ottiene controlli early bpfs (dell %) nei rischi bassi, intermedi e alti, simili alla RT convenzionale con IMRT Dati per 3D CRT, IMRT e tomoterapia sovrapponibili a CK Ecellente controllo biochimico precoce con tossicità acuta e differita (urinaria e rettale) equivalente a quella del frazionamento convenzionale Sintomatologia urinaria e funzioni sessuali a favore della SBRT rispetto alla prostatectomy (a 36 mesi di FU). QOL per sintomi rettali inizialmente peggiore rispetto alla prostatectomia ma con recupero dopo 12 mesi. Evidenti i vantaggi in termini di costi e risparmio di tempo per i pazienti Sono necessari ulteriori studi per perfezionare la selezione pazienti, i vincoli di dose e le modalità di setup.presently SBRT is being directly compared with conventional EBRT and radical prostatectomy Two randomised dstudies currently running PACE trial (Prostate Advances in Comparative Evidence) comparing laparoscopic vs. da Vinci prostatectomy vs. CK prostate SBRT in low and intermediate risk prostate cancer. HYPO-RT-PC trial (Hypo-fractional Radiotherapy for localised Prostrate Cancer) comparing conventional RT vs. seven fractions of 6.1Gy ( 42Gy SBRT) in IR/HR pts. T J Tan et al :Journal of Medical Imaging and Radiation Oncology 58 (2014)

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14 POST OPERATIVE RT November 2014 Comments: -Endoresement of AUA/ASTRO GUIDELINES -adding one qualifying statement: not all candidates for adjuvant or salvage RT have the same risk of recurrence or disease progression, and thus, risk-benefit ratios are not the same for all men. -highest risk for recurrence after radical prostatectomy include men with seminal vesicle invasion, Gleason score 8 to 10, extensive positive margins, and detectable postoperative p PSA. -The decision to administer radiotherapy should be made by the patient and multidisciplinary treatment team, keeping in mind that not all men are at equal risk of recurrence or clinically meaningful disease progression. PERSONALIZED APPROACH BASED ON RISKFACTORS

15 RT postoperatoria : RCT Nel ca. localmente avanzato la RT Adiuvante migliora bned ( %) in 3 trial e la Met.FS ( + 8%) in uno studio; Vantaggi più evidenti in Marg. + La RT di salvataggio dopo ripresa biochimica o recidiva locale è ancora valida in particolare in pazienti con rapido aumento del PSAprima della RT (RT prima che il PSA raggiunga il valore di 2ng/ml; in corso studi per PSA < 0,2ng/ml) H.G. van der Poel: Eur. Urol 2010

16 ADJUVANT RT TREATMENT..ART can improve bpfs after RP for pt3 Pca (10 years: 56% vs 35%). RT-related toxicity was rare and largely mild to moderate. Men with positive surgical margins are the most likely candidates to profit from adjuvant treatment

17 22 centers ct1-3 N0 M0 pt3-4 4N0M0 (PSA, bone scan, chest rx,) ARO TRIAL (A) = WS ; (B) = Adjuvant RT; (C)= Salvage RT Pazienti C-arm : 74 Post PR/preSRT PSA ng/ml n paz. =< 0,1 13 >0,1-0,4 8 0, ,6 2

18 The median FUP time in the 3 trial arms was 112 months Kaplan-Meier probability of clinical relapse-free survival of arm-c pts in the ARO trial. Kaplan-Meier probability of metastasis-free survival of Arm C vs. Arm A+B Kaplan-Meier probability of Overall survival of Arm C vs. Arm A+B

19 Despite immediate SRT with 64 Gy, post-rp PSA persistence correlated with a poor prognosis, including worse overall survival. Patients with PSA persisting after RP are likely to benefit from early aggressive therapy. Radiation therapy in the ARO trial was conventional 3D conformal RT with a median dose of 66 Gy With the use of more recent techniques such as IMRT, dose escalation should be feasible without increasing toxicity Pts with occult dissemination at the time of RP would have a benefit from at least additional HT (i.e. RADICALS Trial) It i h ll f th f t t id tif b i d It remains a challenge for the future to identify by improved imaging or by surrogate markers which pts will profit most from which treatment option

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21 Multicenter Randomized, Open Labelled, Parallel Group Clinical Ti Trials

22 RADICAL TREATMENT RTOG 9910 : RT+OT Multicenter, Randomized, Open Labelled, Parallel Group Clinical Trials Between February 2000 and May ,579 patients were enrolled Prostate/Extraprostatic tumor 70.2 Gy in 39 Fx Iliac nodes (when included) 46.8 Gy in 26 Fx NO IMRT was ALLOWED!!!!!!

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24 RADICAL TREATMENT RT+OT Extending AS to 28 weeks did not affect BFS, DFS, LR or Distant MFS Additional 20 weeks of AS led only to more medication use (with the associated costs) and more endocrine (mainly hot flushing) and sexual adverse effects The RT method prescribed more than a decade ago is no longer recommended!!!

25 RADICAL TREATMENT RT+OT The schedule of 8 weeks of AS before radiotherapy plus 8 weeks of AS during radiotherapy remains a standard of care in intermediate-risk prostate cancer.

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27 CONCLUSION This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer. M.D. Mason et al. : JCO 2015

28 ADT alone is a common treatment for PCa in the USA particularly among elderly patients in their 70s and 80s. Among men age 75 years diagnosed with locally advanced or high-risk screen- detected cancers, 40% receive ADT alone, even though it is not curative, and pts risk debilitating adverse effects» AIM We examined whether the strong survival advantage of ADT plus RT relative to ADT alone reported in the two efficacy RCTs holds in real-world clinical practice

29 Using the SEER-Medicare database PRIMARY COHORT : closest in composition to the eligibility criteria for the two efficacy trials. The RCT cohort included men age 65 to 75 years with clinical stage T2 and moderately or poorly differentiated prostate cancer (WHO grade 2 or 3, respectively) or clinical stage T3 and WHO G1, G2, or G3 PCa. WHO grades 2 and 3 correspond to Gleason scores 5to 7 and 8to 10, respectively ELDERLY COHORT : men age 76 to 85 years with clinical stage T2 and WHO grade 2 or 3 prostate cancer or clinical stage T3 and WHO grade 1, 2, or 3 prostate cancer SCREEN- DETECTED COHORT : men age 65 to 85 years with screen-detected (clinical T1c) highrisk (WHO grade 3) prostate cancer. Retrospective cohort studies on 31,451 patients (Age yrs)

30 RADICAL TREATMENT RT+OT Retrospective cohort studies using the SEER-Medicare database 31,451 patients (Age yrs)

31 RADICAL TREATMENT RT+OT RCTs cohort Yrs cohort Screen Detected cohort LIMITS «Statistical» Study Unknown variables No info about RT field, dose, etc.

32 RADICAL TREATMENT RT+OT HR : 0,43 0,63 Conclusion Older men with locally advanced or screen-detected high-risk prostate cancer who Older men with locally advanced or screen detected high risk prostate cancer who receive ADT alone risk decrements in cause-specific and overall survival.

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