Terapia radiante dopo ripresabiochimica post-prostatectomia

FILIPPO ALONGI

DIRETTORE UOC RADIOTERAPIA ONCOLOGICA,OSPEDALE SACRO CUORE-DON CALABRIA, NEGRAR-VERONA

• 68 anni, iperteso, non diabetico. Pregressa appendicectomia.

• Mitto ipovalido.• iPSA di 27,6ng/ML. • Biopsia prostatica con esito di

adenocarcinoma 3+4 di Gleason ad entrambi i lobi.

• TC addome e Scintigrafia ossea negativi per secondarismi

NOTE ANAMNESTICHE E SITUAZIONE CLINICA ATTUALE

• 68 anni, iperteso, non diabetico. Pregressa appendicectomia

• Mitto ipovalido.• iPSA di 27,6ng/ML. • Biopsia prostatica con esito di

adenocarcinoma 3+4 di Gleason ad entrambi i lobi.

• TC addome e Scintigrafia ossea negativi per secondarismi

TERAPIA PER UN RISCHIO ALTO?

NOTE ANAMNESTICHE E SITUAZIONE CLINICA ATTUALE

• CHIRUGIA?• RADIOTERAPIA ?• ORMONOTERAPIA?• OSSERVAZIONE?

COSA DICONO LE LINEE GUIDA

• Prostatectomia radicale + linfadenectomia pelvica in data 27.11.08 per neoplasia prostatica.

MOTIVAZIONE DELLA SCELTA CLINICA

• Prostatectomia radicale + linfadenectomia pelvica in data 27.11.08 per neoplasia prostatica.

• EI: adenoca gleason 3+4=7 dell'emiprostata destra e sinistra con estensione extra prostatica ed infiltrazione della vescicola seminale sinistra. pT3b,No, Mx. Margini chirurgici indenni.

MOTIVAZIONE DELLA SCELTA CLINICA

TERAPIA ADIUVANTE?• RADIOTERAPIA?• ORMONOTERAPIA?• FOLLOW UP?

COSA DICONO LE LINEE GUIDA

• Esiti funzionali: incontinenza urinaria all' 60%.

• PSA post-operatorio indosabile(<0.002ng/mL)

• EDAR: ipertono sfintere. Loggia disabitata e morbida. Emorroidi esterne non congeste.

COSA DICONO LE LINEE GUIDA

TERAPIA ADIUVANTE?• RADIOTERAPIA?...quindi SI• ORMONOTERAPIA?...Quindi NO• FOLLOW UP?..DOPO RT!!!!!

COSA DICONO LE LINEE GUIDA

Several retrospective and Several retrospective and 3 large prospective 3 large prospective studiesstudies have clarified the role of early adjuvant have clarified the role of early adjuvant radiotherapy (EART) in reducing the risk of radiotherapy (EART) in reducing the risk of recurrence after radical retro-pubic recurrence after radical retro-pubic prostatectomy (RRP) in patients with high-risk prostatectomy (RRP) in patients with high-risk carcinoma of the prostate (hrCaP) as defined carcinoma of the prostate (hrCaP) as defined by the evidence of by the evidence of

• extra-capsular tumor extension, pT3• seminal vesicles involvement.

• and/or surgical margin infiltration R1

Post-operative Radiotherapy Post-operative Radiotherapy in prostate cancer: in prostate cancer:

RATIONALE of RATIONALE of ADJUVANTADJUVANT

Studio randomizzato Pazienti FUP mediano Outcome considerazioni

RTOG 8794(J Urology 2009)

431 12.7 anni Metastasis free survival and overal survival a favore di RT

Vantaggio di sopravvivenza solo a lungo termine

EORTC 22911(Lancet 2012)

1005 10.6 anni RT meglio di osservazione per PFS e LC a 5 anni, a 10 anni perso il vantaggio della RT vs osservazione.

Margini positivi e età < 70 anni: unici forti fattori prognostici a favore di RT.No vantaggio sopravvivenza

ARO 9602(European Urology 2014)

388 10 anni RT meglio di osservazione per PFS

RT riduce il rischio di recidiva biochimica del 51%

POST-OPERATIVE RT:RANDOMIZED TRIALS

MOTIVAZIONE DELLA SCELTA CLINICA

• RADIOTERAPIA?...sconsigliata

dall’urologo per timori di peggioramento incontinenza urinaria

• Attiva FOLLOW UP?..visita urologica ogni 6 mesi e PSA ogni 3…

FOLL0W UP:

• PSA OGNI 3 MESI 0.02ng/mL0.02ng/mL 0.03ng/mL0.05ng/mL0.05ng/mL0.1

0.15ng/mL0.16ng/mL0.20ng/mL0.20ng/mL

SITUAZIONE CLINICA ATTUALE

More effective when PSA is less than 0.5ng/mL..

COSA DICONO LE LINEE GUIDA

“PSA 0.4 ng/mL or greaterPSA 0.4 ng/mL or greater may be the most appropriate cut point to use since a significant number of patients with

lower PSA do not have a continued increase in it”

Amling et al, J Urol 2001Amling et al, J Urol 2001

SALVAGE APPROACH : WHEN?SALVAGE APPROACH : WHEN?

SALVAGE RT FOR PSA RISE: WHAT IS THE CUT OFF???

POST-OPERATIVE RTSALVAGE TIME?

POST-OPERATIVE RTEARLY SALVAGE OR ADIUVANT AT ALL?

EARLY SALVAGE CAN REPLACE UPFRONT

ADJUVANT AT ALL BY ULTRASENSIVE PSA

COMMENTS:

Ultrasensitive serum PSA measurements plays in determining who will develop BCR after radical prostatectomy and, such as, be candidates for secondary treatment.

Postoperative PSA levels achieved significant predictive accuracy already on day 30. PSA >0.073 ng/ml at day 30 increased significantly the risk of BCR

The kinetics of postoperative PSA decline may allowbetter stratification of patients who would benefit from immediate RT.

“A PSA value greater than 0.2 ng/mL is an appropriate cutpoint to define PSA recurrence after RRP”

Freedlan et al, Freedlan et al, Urology 61 : 365-369, 2003Urology 61 : 365-369, 2003

POST-OPERATIVE RTSALVAGE TIME?

PROSTATE GUIDELINES 2013

COSA DICONO LE LINNE GUIDA

SALVAGE APPROACH : WHEN?SALVAGE APPROACH : WHEN?

20122012

SITUAZIONE CLINICA ATTUALE FOLL0W UP:

• PSA OGNI 3 MESI 0.02ng/mL0.02ng/mL 0.03ng/mL0.05ng/mL0.05ng/mL0.1

0.15ng/mL0.16ng/mL0.20ng/mL0.20ng/mL

RT +-OT or observation?

20022002

SALVAGE APPROACH: is really useful?(EBM SALVAGE APPROACH: is really useful?(EBM GRADE C) GRADE C)

…HOWEVER..

….For patients with recurrent prostate cancer after radical prostatectomy,

SALVAGE RT remains the only potentially curative therapy.

Stephenson et al, JAMA 291 : 1325, 2004

SALVAGE APPROACH: is really useful?(EBM SALVAGE APPROACH: is really useful?(EBM GRADE C) GRADE C)

Cosa dicono le Linee-Guida

Cosa dicono le Linee-Guida

The potential benefit The potential benefit deriving from the deriving from the addition of adjuvant addition of adjuvant androgen deprivation androgen deprivation (AAD) to EART remains (AAD) to EART remains to be clarified in term of:to be clarified in term of:

• Timing Timing • DurationDuration• TypeType• Side effectsSide effects

2004200419981998

HORMONAL HORMONAL THERAPY(CONCOMITANT/ADJUVANT)?THERAPY(CONCOMITANT/ADJUVANT)?

SCELTA TERAPEUTICA Effettua Radioterapia: 70 Gy in 35

sedute. Lamenta disuria e modesto tenesmo

autorisolti.

• PSA ogni 3-4 mesi: 0.1ng/mL0.08ng/mL<0.01 ng/mL…•Dopo 1 anno dalla RT: PSA ogni 6 mesi …0.5ng/mL0.60.8ng/mL1.4ng/mL

COSA DICONO LE LINEE GUIDA

PROSTATE GUIDELINES 2013

COSA DICONO LE LINEE GUIDA

SITUAZIONE CLINICA ATTUALE

•PSA ogni 6 mesi …0.5ng/mL0.60.8ng/mL1.4ng/mL

•PSA ogni 3 mesi:…1.5ng/mL1.7

Esegue PET colina

COSA DICONO LE LINEE GUIDA

Paziente di anni 68 anni

• Esegue PET colina che documenta

progressione ossea focale non sintomatica e non a rischio di frattura.

• Attiva terapia ormonale con BAT, attualmente in corso con PSA indosabile.

www.clinicaltrials.govwww.clinicaltrials.gov

Non-systemic Treatment for Patients With Low-Volume Metastatic Prostate Cancer

Phase II RCTPhase II RCT5454 patients needed

Androgen deprivation therapy free survivalAIMS

…….StillOn

Going!!!!

Inclusion Criteria Histologically proven diagnosis• Biochemical relapse a following radical local prostate tx• N1 and M1a/b disease on imaging, with a combined maximum of 3 synchronous lesions (any organs, on choline PET-CT) .• Performance state 0-1• Exclusion of local relapse

Experimental Arm Salvage treatment of metastasesSurgical or RT treatment of metastases

Conventional arm: Active Surveillance

ON GOING CLINICAL TRIALS

STOMP STOMP

StudyStudy

Ghent University Hosp.

2012

EVIDENCE BASED CONCLUSIONS(?)EVIDENCE BASED CONCLUSIONS(?)

Post-operative Radiotherapy in prostate cancer:Post-operative Radiotherapy in prostate cancer: