Prostatectomy, pelvic lymphadenect. Med age 63 years Mean followup 53 months No other cancer related therapy before recurrence. Negative.

Transcription

1 Adjuvante und Salvage Radiotherapie Ludwig Plasswilm Klinik für Radio-Onkologie, KSSG CANCER CONTROL WITH RADICAL PROSTATECTOMY ALONE IN 1,000 CONSECUTIVE PATIENTS Clinical stage T1 and T2 Mean % End Point 5 Yrs 10 Yrs Overall Survival Progression free Survival Progression-free probability curves Prostatectomy, pelvic lymphadenect. Med age 63 years Mean followup 53 months No other cancer related therapy before recurrence pathological stage surgical margin status 92% 71% 80% Negative 37% 36% Positive 7% Hull 2002 ADVANCED TUMOR ADJUVANT RADIOTHERAPY

2 BENEFIT OF ADJUVANT RADIATION THERAPY FOR LOCALIZED PROSTATE CANCER WITH A POSITIVE SURGICAL MARGIN Leibovich 2000 BENEFIT OF ADJUVANT RADIATION THERAPY FOR LOCALIZED PROSTATE CANCER WITH A POSITIVE SURGICAL MARGIN (n = 76) (n = 76) Time from surgery to failure according to study group. A, biochemical, local or systemic failure in all patients. B, biochemical, local or systemic failure in those with base margin involvement. C, biochemical, local or systemic failure in those with apex margin involvement. D, local or systemic failure in all patients Leibovich 2000 Randomized Trials EORTC SWOG 8794 ARO / AUO AP 09/95

3 Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911) Bolla 2005 Trial profile Bolla 2005 Cumulative incidence of loco-regional failures 15.4 % 5.4 % p < Bolla 2005

4 Clinical progression-free survival Biochemical progression-free survival Bolla 2005 Identification of Patients With Prostate Cancer Who Benefit From Immediate Postoperative Radiotherapy: EORTC van der Kwast 2007 Forest plot for the individual factors predictive of treatment benefit in patients with post-operative prostatespecific antigen 0.2 ng/ml. van der Kwast 2007

5 Biochemical progression-free survival by surgical margin status and allocated treatment N, number of patients; O, number of events; SM/, surgical margin negative/positive; W&S, wait-and-see group (control); RT, irradiation. van der Kwast 2007 Treatment effect on biochemical progression-free survival by review margin status and localization of the positive margin (A) in all patients and (B) in patients with postoperative prostate-specific antigen (PSA) 0.2 ng/ml. van der Kwast 2007 Biochemical progression-free survival according to margin status and localization for patients (A) in the control arm and (A) in the immediate postoperative irradiation arm. N, number of patients; O, number of events. van der Kwast 2007

6 Phase III Postoperative Adjuvant Radiotherapy After Radical Prostatectomy Compared With Radical Prostatectomy Alone in pt3 Prostate Cancer With Postoperative Undetectable Prostate-Specific Antigen: ARO / AUO AP 09/95 Wiegel 2009 Trial profile HT, hormonal treatment; PSA, prostate-specific antigen; RT, radiotherapy. Wiegel 2009 Biochemical progression-free survival of all patients with undetectable prostate-specific antigen after radical prostatectomy (intention-to-treat group 2 [ITT2]) Biochemical progression-free survival of all randomly assigned patients (n 385; intention-to-treat group 1 [ITT1]) Wiegel 2009

7 Treatment effects by prognostic factors RFS, recurrence-free survival; PSA, prostate-specific antigen; RP, radical prostatectomy. Wiegel 2009 Adjuvant Radiotherapy for Pathologically Advanced Prostate Cancer A Randomized Clinical Trial (SWOG 8794) Thompson 2006 Flow of Patients in the Study Thompson 2006

8 PSA Relapse-Free, Recurrence-Free, and Overall Survival and Freedom From Hormonal Treatment in Patients Randomized to Adjuvant Radiotherapy or Observation Thompson 2006 Metastasis-Free Survival in Patients Randomized to Adjuvant Radiotherapy of Observation Thompson 2006 Update of SWOG 8794: Adjuvant Radiotherapy for pt3 Prostate Cancer Improves Metastasis Free Survival median follow up of 11.5 years Adjuvant radiation significantly improved metastasis free survival (p = 0.036; HR 0.74, 95% CI 0.56, 0.98), the study s primary endpoint. Overall survival was improved with radiation (p = 0.053; HR 0.76, 95% CI 0.57, 1.00). Fifteen year metastasis free survival was 46% for radiation and 38% for observation. For overall survival, it was 47% and 37%, respectively. As previously reported, radiation therapy also significantly reduced biochemical and local failure as well as the need for subsequent androgen ablation (all p<0.005). Global quality of life evaluation showed statistically significant increases in patient-reported GU-specific symptoms and healthrelated quality of life for the radiotherapy arm compared to observation at 6 weeks and 2 years Swanson, ASTRO 2008

9 PSA ELEVATION FOLLOWING RADICAL PROSTATECTOMY SALVAGE RADIOTHERAPY RADIOTHERAPY FOR ISOLATED SERUM PROSTATE SPECIFIC ANTIGEN ELEVATION AFTER PROSTATECTOMY FOR PROSTATE CANCER Disease outcome in 166 patients treated with radiotherapy for elevated postoperative serum PSA level 46%! Biochemical relapse-free probability after radiotherapy according to serum PSA before radiotherapy Pisansky 2000 RADIOTHERAPY FOR ISOLATED SERUM PROSTATE SPECIFIC ANTIGEN ELEVATION AFTER PROSTATECTOMY FOR PROSTATE CANCER Biochemical relapse-free probability after radiotherapy according to tumor grade Biochemical relapse-free probability after radiotherapy according to pathological tumor classification Pisansky 2000

10 Salvage Radiotherapy for Recurrent Prostate Cancer After Radical Prostatectomy 501 pts with detectable and increasing PSA level Multivariable Cox Regression Analysis of Predictors of PSA ( , five US centers) Progression After Salvage Radiotherapy Med follow-op 45 months Kaplan-Meier Estimate of Progression-Free Probability After Salvage Radiotherapy n = 501 (x) x x x x x 39% Pts with no adverse features had a 4-year PFP of 77% Stephenson 2004 Predicting the Outcome of Salvage Radiation Therapy for Recurrent Prostate Cancer After Radical Prostatectomy (A) Kaplan-Meier estimate of the overall progression-free probability after salvage radiotherapy. (B) Progression-free probability after salvage radiotherapy stratified by preradiotherapy prostate-specific antigen 0.50 or less (blue), 0.51 to 1.00 (yellow), 1.01 to 1.50 (gray), and more than 1.50 ng/ml (red). Stephenson 2007 Predicting the Outcome of Salvage Radiation Therapy for Recurrent Prostate Cancer After Radical Prostatectomy (A) Kaplan-Meier estimate of the overall progression-free probability after salvage radiotherapy. (B) Progression-free probability after salvage radiotherapy stratified by preradiotherapy prostate-specific antigen 0.50 or less (blue), 0.51 to 1.00 (yellow), 1.01 to 1.50 (gray), and more than 1.50 ng/ml (red). Stephenson 2007

11 (A) Pretreatment nomogram predicting 6-year progression-free probability after salvage radiotherapy for prostate-specific antigen (PSA) recurrence after radical prostatectomy. (B) Calibration of the nomogram. Dashed line indicates reference line where an ideal nomogram would lie. Solid line indicates the performance of the current nomogram. Dots are quartiles of our data set. Instructions: Locate the patient s Gleason score on the respective axis. Draw a straight line up to the Points axis to determine how many points toward disease recurrence that the patient receives for his or her Gleason score. Repeat this process for the other 10 disease and reatment parameters. Sum the points and locate this number on the Total Points axis. Draw a straight line down to find the patient s probability of remaining free of disease progression at 6 years after salvage radiotherapy, provided the patient does not die of another cause first Stephenson 2007 ADJUVANT VERSUS SALVAGE IRRADIATION AFTER RADICAL PROSTATECTOMY? BIOCHEMICAL DISEASE-FREE SURVIVAL FOLLOWING ADJUVANT AND SALVAGE IRRADIATION AFTER RADICAL PROSTATECTOMY 76 pts, RP, adjuvant / salvage RT, (med. 60 Gy) / (med 65 Gy) Kaplan-Meier estimate of overall biochemical disease-free survival (bned) after adjuvant or salvage RT n = 35 Adjuvant RT n = 41 Salvage RT med. pre-rt PSA: pts. Pre-RT PSA > 1.0 Kalapurakal 2002

12 Predominant Treatment Failure in Postprostatectomy Patients Is Local: Analysis of Patterns of Treatment Failure in SWOG 8794 PSA Failure-Free Rates by Post-RP PSA Subgroup Among Patients Who Received Immediate or Delayed Radiation (adjuvant) (salvage) (adjuvant) (salvage) RP, radical prostatectomy; PSA, prostate-specific antigen; XRT, radiation therapy. *Time to PSA failure: registration date to date of first PSA 0.4 ng/ml. Time to PSA failure: date of initiation of salvage RT to first subsequent date of PSA 0.4 ng/ml. Swanson 2007 BIOPSY- PROVEN LOCAL RECURRENCE Prediction of Response to Salvage Radiation Therapy in Patients With Prostate Cancer Recurrence After Radical Prostatectomy stratified by the median preradiation serum PSA level 95 pts had undergone prostatectomy ( ) 50 pts received salvage RT (med. 66 Gy) 40 pts with biopsy-proven local recurrence 10 pts with PSA recurrence (1 pt. excluded) n = 49 24% stratified by the median postrecurrence serum PSA doubl. time Leventis 2001

13 TOXICITY? ARO / AUO AP 09/95 Altogether, the cumulative rate of adverse effects for bladder and rectum (grade 1) was 21.9% in the RT arm and 3.7% in the wait-and-see group. There was only one event of grade 3 toxicity (bladder). No grade 4 events were recorded. There were three events (2%) for grade 2 genitourinary adverse effects in the RT arm compared with none in the other arms. In addition, two grade 2 GI adverse effects (1.4%) were seen in the RTarm compared with none in the other arms. Wiegel 2009 p values indicate comparison of wait-andsee with irradiation groups. EORTC Cumulative incidence of late complications No events of grade 4 toxicity were reported. Bolla 2005 Tox. Grade III / (IV) Adj RT (60 Gy): < 1 % Salvage RT (64-66%) 1-5 %