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949 INFLUENCE ADJUVANT VS. SALVAGE RADIOTHERAPY ON CONTINENCE AFTER RADICAL PROSTATECTOMY
e386
THE JOURNAL OF UROLOGY姞
Vol. 187, No. 4S, Supplement, Monday, May 21, 2012
948 OPTIMAL TIMING OF EARLY VERSUS DELAYED ADJUVANT RADIOTHERAPY FOLLOWING RADICAL PROSTATECTOMY FOR LOCALLY ADVANCED PROSTATE CANCER Keith Kowalczyk*, Washington, DC; Xiangmei Gu, Paul Nguyen, Stuart Lipsitz, Hua-yin Yu, Boston, MA; Sean Collins, Washington, DC; Jim Hu, Boston, MA INTRODUCTION AND OBJECTIVES: Although post-prostatectomy adjuvant radiation therapy (ART) has shown survival benefits for ⬎pT3 disease, optimal ART timing remains unknown as randomized controlled trials have used arbitrary cut-points based on study design. Using a population-based approach, we characterize outcomes of early vs. delayed ART as well as the optimal timing of ART following radical prostatectomy (RP) for locally advanced disease. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data from 1995-2007, we identified 1056 men with ⬎pT3N0 disease receiving early (⬍4 months post-RP, n⫽464) vs. delayed (4-12 months post-RP, n⫽592) ART following RP. Baseline demographic and tumor characteristics were recorded and compared. Propensity-score methods were used to compare overall mortality, prostate cancer-specific mortality (PCSM), bone-related events (defined as bone metastasis and/or pathologic fracture), and salvage hormonal therapy utilization (⬎12 months following initiation of ART). Additionally, we used the maximal statistic approach to determine time cut-points with most significant ART benefit. RESULTS: Early vs. delayed ART was associated with improved PCSM (0.71 vs. 2.05 events per 100 person-years, p⫽0.024) for T3b disease and fewer bone-related events for T3a disease with negative margins (T3aNM, 0.92 vs. 2.50 events per 100 person-years, p⫽0.008). Administering ART ⬎11 months post-RP for T3aNM (HR 15.6, p⫽0.022) and ⬎6 months post-RP for T3b (HR 2.74, p⫽0.015) was associated with worse PCSM. Delaying ART ⬎5 months for T3aNM (HR 2.52, p⫽0.005) and ⬎7 months for T3a disease with positive margins (HR 2.26, p⫽0.007) was associated with increased bone-related events. CONCLUSIONS: Initiating ART ⬍6 months post-RP for T3b disease and ⬍11 months post-RP for T3aNM disease is associated with improved PCSM. Early ART for T3a, regardless of margin status, is also associated with fewer bone-related events. Our populationbased findings complement randomized trials designed with fixed ART timing, and aids providers and patients considering ART. Results of maximal statistic approach to calculate adjusted post-radical prostatectomy time cut-points when adjuvant radiation therapy has the most significant benefit Months Hazard Ratio p-value T3a NEGATIVE MARGIN Overall mortality Prostate-cancer specific mortality
3
1.63
0.254
Source of Funding: This study was funded by a Department of Defense Prostate Cancer Physician Training Award (W81XWH-08-1-0283) presented to Dr. Hu
949 INFLUENCE ADJUVANT VS. SALVAGE RADIOTHERAPY ON CONTINENCE AFTER RADICAL PROSTATECTOMY Joanne Nyarangi-Dix*, Johannes Steimer, Hildegard Jakobi, Sascha Pahernik, Boris Hadaschik, Markus Hohenfellner, Heidelberg, Germany INTRODUCTION AND OBJECTIVES: Adjuvant radiotherapy (ART) in high risk and salvage radiation therapy (SRT) in case of biochemical recurrence are common settings for EBRT after radical prostatectomy (RP). We primarily evaluated the effect of both approaches on continence. METHODS: Upon authorization by our institutional review board we identified 309 men from the Heidelberg prospective tumour data bank. ART was defined as RT ⬍ 4 months and SRT as RT ⬎ 4 months after RP. We retrieved data on pre-, postoperative patient and tumour characteristics as well as postoperative therapies like RT from our institutional prospective tumour data bank. A telephone survey for evaluation of continence was done using the ICIQ-SF-Questionnaire. Study subjects were also further questioned e.g. on whether present continence was similar, better or worse than the situation prior to RT. Analysis was made with the IBM-SPSS software and Pearson Chisquare, Students⬘ t-test and Fischer⬘s exact tests. RESULTS: 128 received ART and the other 181 SRT. Mean age of all patients at the time of RT was 65.4 (sd 6.2) yrs. Statistically significant differences in the distribution between the 2 groups were found in age at RT, preoperative prostate volume, post-RT-PSA, progression free survival , lymph node status, Gleason score and surgical margins. The difference in the distribution of applied radiation dose, age at RP, technique of RP, preoperative PSA-Value, length of RT, cancer specific survival, pre-RT-continence was not statistically significant. Form and overall grade continence before and after ART and SRT was also not statistically significant. In a sub-analysis, only 2% of the patients, all from the ART group, indicated an improvement of continence in the period after RT; this was statistically, significant. The other 98% reported unchanged or worsened continence. There was no significant difference in this distribution between the 2 groups. CONCLUSIONS: According to our literature review of the past 10 years, this is the first study specifically analysing the effect of ART vs. SRT on continence. The time of RT seems to have no significant influence on continence after RP. At the same time, maintenance of the natural course of post-prostatectomy continence including spontaneous improvement seems possible. Should this thesis be confirmed in prospective studies, early ART and intraoperative RT-regimes can be safely evaluated with the goal of improving survival of high risk prostate cancer without compromising continence.
11
15.60
0.022
Bone-related events
5
2.52
0.005
Salvage hormonal therapy
4
1.78
0.039
7
0.52
0.157
10
4.89
0.267
Bone-related events
7
2.25
0.007
Salvage hormonal therapy
4
1.57
0.093
950
12
7.34
0.318
IMPACT OF PRIOR LOCAL THERAPY ON SURVIVAL IN MEN RECEIVING CHEMOTHERAPY FOR METASTATIC PROSTATE CANCER.
T3a POSITIVE MARGIN Overall mortality Prostate-cancer specific mortality
T3b Overall mortality Prostate-cancer specific mortality
6
2.74
0.015
10
0.45
0.243
8
2.48
⬍ 0.001
Overall mortality
3
0.38
0.013
Prostate-cancer specific mortality
6
6.10
0.021
Bone-related events
5
0.42
0.087
Salvage hormonal therapy
6
2.28
0.041
Bone-related events Salvage hormonal therapy T4
Source of Funding: None
Oluwakayode Adejoro, Sean Elliott, Badrinath Konety*, Minneapolis, MN INTRODUCTION AND OBJECTIVES: The benefit of prior local therapy in the form of radiation or radical prostatectomy in men who subsequently go on to develop metastatic disease and receive chemotherapy is not well characterized. We sought to assess the impact of a previously treated primary tumor in the prostate on survival following androgen suppression therapy and chemotherapy for metastatic prostate cancer in men who progress to develop metastatic disease.
THE JOURNAL OF UROLOGY姞
Vol. 187, No. 4S, Supplement, Monday, May 21, 2012
948 OPTIMAL TIMING OF EARLY VERSUS DELAYED ADJUVANT RADIOTHERAPY FOLLOWING RADICAL PROSTATECTOMY FOR LOCALLY ADVANCED PROSTATE CANCER Keith Kowalczyk*, Washington, DC; Xiangmei Gu, Paul Nguyen, Stuart Lipsitz, Hua-yin Yu, Boston, MA; Sean Collins, Washington, DC; Jim Hu, Boston, MA INTRODUCTION AND OBJECTIVES: Although post-prostatectomy adjuvant radiation therapy (ART) has shown survival benefits for ⬎pT3 disease, optimal ART timing remains unknown as randomized controlled trials have used arbitrary cut-points based on study design. Using a population-based approach, we characterize outcomes of early vs. delayed ART as well as the optimal timing of ART following radical prostatectomy (RP) for locally advanced disease. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data from 1995-2007, we identified 1056 men with ⬎pT3N0 disease receiving early (⬍4 months post-RP, n⫽464) vs. delayed (4-12 months post-RP, n⫽592) ART following RP. Baseline demographic and tumor characteristics were recorded and compared. Propensity-score methods were used to compare overall mortality, prostate cancer-specific mortality (PCSM), bone-related events (defined as bone metastasis and/or pathologic fracture), and salvage hormonal therapy utilization (⬎12 months following initiation of ART). Additionally, we used the maximal statistic approach to determine time cut-points with most significant ART benefit. RESULTS: Early vs. delayed ART was associated with improved PCSM (0.71 vs. 2.05 events per 100 person-years, p⫽0.024) for T3b disease and fewer bone-related events for T3a disease with negative margins (T3aNM, 0.92 vs. 2.50 events per 100 person-years, p⫽0.008). Administering ART ⬎11 months post-RP for T3aNM (HR 15.6, p⫽0.022) and ⬎6 months post-RP for T3b (HR 2.74, p⫽0.015) was associated with worse PCSM. Delaying ART ⬎5 months for T3aNM (HR 2.52, p⫽0.005) and ⬎7 months for T3a disease with positive margins (HR 2.26, p⫽0.007) was associated with increased bone-related events. CONCLUSIONS: Initiating ART ⬍6 months post-RP for T3b disease and ⬍11 months post-RP for T3aNM disease is associated with improved PCSM. Early ART for T3a, regardless of margin status, is also associated with fewer bone-related events. Our populationbased findings complement randomized trials designed with fixed ART timing, and aids providers and patients considering ART. Results of maximal statistic approach to calculate adjusted post-radical prostatectomy time cut-points when adjuvant radiation therapy has the most significant benefit Months Hazard Ratio p-value T3a NEGATIVE MARGIN Overall mortality Prostate-cancer specific mortality
3
1.63
0.254
Source of Funding: This study was funded by a Department of Defense Prostate Cancer Physician Training Award (W81XWH-08-1-0283) presented to Dr. Hu
949 INFLUENCE ADJUVANT VS. SALVAGE RADIOTHERAPY ON CONTINENCE AFTER RADICAL PROSTATECTOMY Joanne Nyarangi-Dix*, Johannes Steimer, Hildegard Jakobi, Sascha Pahernik, Boris Hadaschik, Markus Hohenfellner, Heidelberg, Germany INTRODUCTION AND OBJECTIVES: Adjuvant radiotherapy (ART) in high risk and salvage radiation therapy (SRT) in case of biochemical recurrence are common settings for EBRT after radical prostatectomy (RP). We primarily evaluated the effect of both approaches on continence. METHODS: Upon authorization by our institutional review board we identified 309 men from the Heidelberg prospective tumour data bank. ART was defined as RT ⬍ 4 months and SRT as RT ⬎ 4 months after RP. We retrieved data on pre-, postoperative patient and tumour characteristics as well as postoperative therapies like RT from our institutional prospective tumour data bank. A telephone survey for evaluation of continence was done using the ICIQ-SF-Questionnaire. Study subjects were also further questioned e.g. on whether present continence was similar, better or worse than the situation prior to RT. Analysis was made with the IBM-SPSS software and Pearson Chisquare, Students⬘ t-test and Fischer⬘s exact tests. RESULTS: 128 received ART and the other 181 SRT. Mean age of all patients at the time of RT was 65.4 (sd 6.2) yrs. Statistically significant differences in the distribution between the 2 groups were found in age at RT, preoperative prostate volume, post-RT-PSA, progression free survival , lymph node status, Gleason score and surgical margins. The difference in the distribution of applied radiation dose, age at RP, technique of RP, preoperative PSA-Value, length of RT, cancer specific survival, pre-RT-continence was not statistically significant. Form and overall grade continence before and after ART and SRT was also not statistically significant. In a sub-analysis, only 2% of the patients, all from the ART group, indicated an improvement of continence in the period after RT; this was statistically, significant. The other 98% reported unchanged or worsened continence. There was no significant difference in this distribution between the 2 groups. CONCLUSIONS: According to our literature review of the past 10 years, this is the first study specifically analysing the effect of ART vs. SRT on continence. The time of RT seems to have no significant influence on continence after RP. At the same time, maintenance of the natural course of post-prostatectomy continence including spontaneous improvement seems possible. Should this thesis be confirmed in prospective studies, early ART and intraoperative RT-regimes can be safely evaluated with the goal of improving survival of high risk prostate cancer without compromising continence.
11
15.60
0.022
Bone-related events
5
2.52
0.005
Salvage hormonal therapy
4
1.78
0.039
7
0.52
0.157
10
4.89
0.267
Bone-related events
7
2.25
0.007
Salvage hormonal therapy
4
1.57
0.093
950
12
7.34
0.318
IMPACT OF PRIOR LOCAL THERAPY ON SURVIVAL IN MEN RECEIVING CHEMOTHERAPY FOR METASTATIC PROSTATE CANCER.
T3a POSITIVE MARGIN Overall mortality Prostate-cancer specific mortality
T3b Overall mortality Prostate-cancer specific mortality
6
2.74
0.015
10
0.45
0.243
8
2.48
⬍ 0.001
Overall mortality
3
0.38
0.013
Prostate-cancer specific mortality
6
6.10
0.021
Bone-related events
5
0.42
0.087
Salvage hormonal therapy
6
2.28
0.041
Bone-related events Salvage hormonal therapy T4
Source of Funding: None
Oluwakayode Adejoro, Sean Elliott, Badrinath Konety*, Minneapolis, MN INTRODUCTION AND OBJECTIVES: The benefit of prior local therapy in the form of radiation or radical prostatectomy in men who subsequently go on to develop metastatic disease and receive chemotherapy is not well characterized. We sought to assess the impact of a previously treated primary tumor in the prostate on survival following androgen suppression therapy and chemotherapy for metastatic prostate cancer in men who progress to develop metastatic disease.