- Email: [email protected]
304Influence of deferred treatment with curative intent on progression free survival rates in prostate cancer
302
301 GENERAL AND DISEASE SPECIFIC HEALTH RELATED QUALITY OF LIFE AFTER RADICAL PROSTATECTOMY OR EXTERNAL BEAM RADIOTHERAPY FOR LOCALIZED PROSTATE CANCER: A CONTROLLED PROSPECTIVE STUDY
HISTOPATHOLOGY HG PIN-DETECTED
Di Stasi S.M?, Giannantoni A.a, Storti L. 1, Chiarotti F.3, Artisan[ F. 1, Sansalone SJ, Forte F?, Jannini E.A.4, Zampa G.s, Vespasian[ G?
University Hospital Leuven, Urology, Leuven, Belgium
'Tor Vergata University, Department of Urology, Rome, Italy, 2University of Pemgia, Department of Urology, Pemgia, Italy, 3Istituto Super[ore di Sanita', Department of Biostatistics, Rome, Italy, 4University of l'Aquila, Department of Experimental Medicine, l'Aquila, Italy, aS. Giacemo Hospital, Operative Unit of Onceiogy, Rome, Italy
INTRODUCTION & OBJECTIVES: The finding of isolated High Grade Prostatic Intraepithelial Neoplasia (HG PIN) in prostate biopsies is a predictive t'actor for the detection of prostate cancer in subsequent biopsies. However, it is not well studied whether the pathological features of these tumours can be predicted by the number of repeat biopsies. We performed a prospective trial to evaluate histopathological parameters in specimens of patients with HG PIN on initial biopsies who underwent a radical prostatectomy for the detection of prostate cancer in repeat biopsies.
INTRODUCTION & OBJECTIVES: General and disease specific health-related quality of life (HRQOL) were assessed within the framework of a randomized trial to compare the outcomes of radical retropubie prostatectomy (RP) versus external beam radiotherapy (EBRT) in patients with clinically localized prostate cancer. MATERIAL & METHODS: Between 1997 and 2001, 137 patients were randomly treated with RP (n=70) or EBRT (n=67). Both groups included patients with comparable baseline characteristics. Before treatment and at 1, 3, 6, 12 and 24 months of follow-up, 96 valuable patients, 47 in RP and 49 in EBRT group, completed a questionnaire assessing the general HRQOL of life and specific changes in bowel, urinary and sexual functions. The questionnaire was validated by a test-retest pilot study. The repeated measures analysis of variance and analysis of covariance were conducted on all outcomes measures. All statistical tests were two-sided. RESULTS: In the first month after treatment, the RP group reported a significant decrease in general HRQOL than that observed in patients receiving EBRT (p<0.00l). At 3 months of follow-up, the general HRQOL differences among the groups were less striking, and at i2 months, the scores were not statistically different from the baseline scores in both treatment groups (p=0.431). After treatment the RP group showed a significantly lower urinary function score than the EBRT group (p<0.001). Urinary function improved with time during the first year after RP but remained fairly constant during year 2. Approximately 10.6% of RP and 2.9% of EBRT patients (OR-3.9, 95% confidence interval [CI]-1.4 to 5.9) were incontinent at 2 years. The EBRT group was associated with significant worse bowel fimction than the RP group throughout follow-up time (p<0.001). Approximately 26.5% of EBRT and 6.1% of RP patients (OR=0.23, 95% CI-0.1 to 0.5) had bowel dysfunction at 2 years. Sexual function was significantly better in EBRT than RP group just after treatment (p<0.001). During follow-up, the EBRT group showed a modest but statistically significant decline in sexual function, whereas the RP group improving over time. However, at 2 years sexual dysfunction was more prevalent in the RP than in the EBRT group (70.2% versus 61.2%; OR-2.5, 95% CI=1.6 to 3.8). The bothersome scores generally correlated with the functionality scores.
CONCLUSIONS: A significant decrease in general HRQOL was evident only in the first month after RP. Patients undergoing RP report significantly worse urinary function, but better bowel function than those treated with EBRT. Both groups have a decline in sexual function throughout the post-treatment period. During the follow-up patients treated with EBRT began to show a continuing decline in erectile function.
Pi8 LOCAUSEDPROSTATECAN~ERiNONSUR6iC~~DiCALTREATMENTSII
OF RADICAL PROSTATECTOMY PROSTATE CANCER
Joniau S., Goeman L., Van Poppel H.
MATERIAL & METHODS: 106 subsequent patients with isolated HG PIN on standard octant prostate biopsies were included in the study. A total of 78 patients was further evaluated and underwent repeat biopsies at 3 months (visit 2 = V2) and 6 months (visit 3 = V3). Prostate cancer was found in 16.6% (13/78) of patients at V2, and in 19.2% (15/78) of patients at V3. Total cancer detection was 35.8%. Of the 28 patients in whom prostate cancer was detected, a radical prostatectomy was performed in 24 (11 in the V2 and 13 in the V3 group). RESULTS: In 13 patients of the V2 group and 11 patients of the V3 group, a radical prostatectomy was performed. Histopathological parameters were recorded for each group. pT2
pT3
Section
T volume] T voluJylc
Gleason
Gleason
_>Sc°re7
Visit 2 (n=13)
38.5% (n=5)
61.5% (n=8)
92.3% (n=12)
7.7% :(n=l)
15.4% (n=2)
30.8% (n=4)
69.2% (n=9)
Visit 3 (n=l 1)
90.9% (n=10)
9.1% (n=l)
100% (n=ll)
0% (n=0)
0% (n=0)
63.6% (n=7)
36.4% (n=4)
PosMargins < 0,5 ml i > 0,5 ml
C O N C L U S I O N S : Although we found similar cancer detection rates in first and second repeat biopsies following the diagnosis of isolated H G PIN in standard octant biopsies, the pathological features o f the detected tumours are quite different when assessed in radical prostatectomy specimens. It is concluded that a less aggressive approach is warranted in patients who have cancer at second (or later) repeat biopsies.
304
303
P A T I E N T S W I T H A S Y M P T O M A T I C P R O S T A T E C A N C E R T.0-4 N.0-2 M.0 NOT SUITABLE FOR LOCAL DEFINITIVE TREATMENT: DO THEY NEED IMMEDIATE ANDROGEN DEPRIVATION?
S P E C I M E N S IN
INFLUENCE OF DEFERRED TREATMENT WITH CURATIVE INTENT O N P R O G R E S S I O N F R E E S U R V I V A L R A T E S IN P R O S T A T E C A N C E R Roemeling S., De '?ties S., Gosselaar C., Schroeder F., ERSPC, Rotterdam, The Netherlands
Studer U.E?, Whelan p2, Albrecht W. 3, Casselman j.4, De Reijke T. s, Hanri D. 6, Loidl W. 7, Isorna S. s, Sundaram S.K. 9, Debois M. 1°, Collette L. 1°, EORTC Genitourinary Group ~University Hospital of Bern, Department of Urology, Bern, Switzerland, aSt. James Hospital, Department of Urology, Leeds, United Kingdom, 3Rudolfstiftung, Department of Urology, Vienna, Austria, 4Belgische Vereniging veer Urologie, Department of Urology, Oostende, Belgium, SAcademisch Medisch Centrum, Department of Urology, Amsterdam, The Netherlands, 6Universit~tsspital Z/Jrich, Department of Urology, Ztlrich, Switzerland, 7Krankenhaus Barmherzige Schwestern, Department of Urology, Linz, Austria, SHospital N.S. Del Pine, Department of Urology, Las Palmas, Spain, 9, -, Wakefield, United Kingdom, mEORTC, Data Center, Brussels, Belgium INTRODUCTION & OBJECTIVES: In patients with localized N0-2 prostate cancer EORTC trial 30891 compared prospectively immediate endocrine treatment with orchiectomy or LH-RH analog (Buserelin® 2-monthly depot) to deferred treatment initiated at the time of symptomatic disease progression or life-threatening complications. MATERIAL & METHODS: The trial aimed to demonstrate equivalent overall survival. Data from 985 patients randomized between 1990 and 1999 were used. RESULTS: Patients were 73 years old in median (52-81) and characteristics were well balanced in the two groups. After a median follow-up of 7.8 years, 541 deaths were reported. The trial failed to demonstrate equivalent survival: the 95% confidence interval for the relative increase in overall mortality with deferred treatment compared to immediate treatment ranged from +5% to +48%. The absolute increase in death rate was +7% at 5 years and +11% at 10 years. Survival was thus better on immediate treatment. The data also suggest that mortality definitively or probably due to prostate cancer was not substantially increased, irrespective whether the cause of death was assessed by the local investigator, the study coordinator or two independent reviewers (Pea mortality was 29.0% vs. 26.2% on deferred and immediate, resp.). Which competing cause of death contributed to the difference in overall survival is difficult to assess as multiple factors are often present in this old population, but no difference in cardiovascular event rate was observed. With the available follow-up data, time from entry on study to the first symptoms after onset of hormonal treatment seemed not to be influenced by treatment policy, neither was the time to appearance of first objective progression after onset of immediate or deferred hormonal treatment. In the patients who started deferred hormonal treatment, treatment was initiated in median 3.2 years after entry on study. On deferred treatment 126 patients died without needing treatmem (44% of the deceased cases, 25% of all patients). CONCLUSIONS: Overall survival was better with immediate androgen deprivation. The leading cause for this difference is unknown, however, no significant difference was found in P e a nor overall symptom free survival. The data suggest that the deferred approach may spare the burden of the treatment to a substantial number of patients.
European Urology Supplements 4 (2005) No. 3, pp. 78
Erasmus Me, Urology, Rotterdam, The Netherlands INTRODUCTION & OBJECTIVES: The optimal moment for definitive curative treatment for localized prostate cancer in men initially managed on a watchful waiting policy remains controversial. The goal of this study was to evaluate whether deferred treatment in screen detected cases leads to more biochemical progression compared to matched cases who directly received treatment with curative intent. MATERIAL & METHODS: In this case-control study, patients initially monitored on a watchful waiting policy were matched with controls who directly received treatment with curative intent. The choice of initial treatment was patient desire or physician advice. All cases were diagnosed with prostate cancer from September '94 through July '02 in the screen arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam. To every case two controls were matched for age, PSA, number of previous screen tests, biopsy Gleason score and clinical T-stage. The control cases were randomly selected. Endpoints were biochemical progression (BP) and (disease specific) mortality. BP after radical prostatectomy (RP) was defined as two consecutive PSA values of 0.2 ng/mI or higher and three consecutive PSA increases (ASTRO criteria) after radiotherapy (RT). RESULTS: Of 209 men managed on a watchful waiting policy 27 (12.9%) received deferred treatment (DT) with curative intent. Six men received a tiP and 21 RT. These cases were compared with 52 control patients, as one RT case could not be matched. Median age (range) of the RP and RT group was 69.5 years mad 67.7 years, median PSA at diagnosis 3.8 ng/ml and 4.8 ng/ml. Most cases had a Gleason score of 3 + 3 (77.0%). Except for 1 patient all men had organ confined disease on digital rectal examination, with 84.6% having T1C. Median time to DT was 8.2 (2.4-53.0) months in RP and 19.3 (12.0-58.6) months in RT. Median follow-up after DT respectively was 73.1 (47.1-85.0) and 21.0 (5.7-57.2) months. Total follow-up of the controls treated with RP or RT was 75.3 (18.9-99.5) or 40.4 (10.8-103.6) months. One case treated with deferred RP had BP while none of the RT treated cases had BP of disease. In the control group 3 (25.0%) patients had BP after RP and 2 (5%) after RT. No case in the RP group died, while one patient in the deferred RT group died. In the RP control group 2 (16.7%) patients died compared to 3 (7.5%) in the RT control group. None of these patients died of prostate cancer. CONCLUSIONS: Biochemical progression rates were not higher in patients with deferred treatment compared to those directly treated with curative intent. This descriptive study thus supports former evidence that deferring treatment in patients with selected, favourable prostate cancer characteristics does not influence the time of biochemical progression. If these preliminary results turn out to be consistent after longer follow-up, treatment related sideeffects can be postponed, resulting in increased quality of life without compromising disease specific survival.
301 GENERAL AND DISEASE SPECIFIC HEALTH RELATED QUALITY OF LIFE AFTER RADICAL PROSTATECTOMY OR EXTERNAL BEAM RADIOTHERAPY FOR LOCALIZED PROSTATE CANCER: A CONTROLLED PROSPECTIVE STUDY
HISTOPATHOLOGY HG PIN-DETECTED
Di Stasi S.M?, Giannantoni A.a, Storti L. 1, Chiarotti F.3, Artisan[ F. 1, Sansalone SJ, Forte F?, Jannini E.A.4, Zampa G.s, Vespasian[ G?
University Hospital Leuven, Urology, Leuven, Belgium
'Tor Vergata University, Department of Urology, Rome, Italy, 2University of Pemgia, Department of Urology, Pemgia, Italy, 3Istituto Super[ore di Sanita', Department of Biostatistics, Rome, Italy, 4University of l'Aquila, Department of Experimental Medicine, l'Aquila, Italy, aS. Giacemo Hospital, Operative Unit of Onceiogy, Rome, Italy
INTRODUCTION & OBJECTIVES: The finding of isolated High Grade Prostatic Intraepithelial Neoplasia (HG PIN) in prostate biopsies is a predictive t'actor for the detection of prostate cancer in subsequent biopsies. However, it is not well studied whether the pathological features of these tumours can be predicted by the number of repeat biopsies. We performed a prospective trial to evaluate histopathological parameters in specimens of patients with HG PIN on initial biopsies who underwent a radical prostatectomy for the detection of prostate cancer in repeat biopsies.
INTRODUCTION & OBJECTIVES: General and disease specific health-related quality of life (HRQOL) were assessed within the framework of a randomized trial to compare the outcomes of radical retropubie prostatectomy (RP) versus external beam radiotherapy (EBRT) in patients with clinically localized prostate cancer. MATERIAL & METHODS: Between 1997 and 2001, 137 patients were randomly treated with RP (n=70) or EBRT (n=67). Both groups included patients with comparable baseline characteristics. Before treatment and at 1, 3, 6, 12 and 24 months of follow-up, 96 valuable patients, 47 in RP and 49 in EBRT group, completed a questionnaire assessing the general HRQOL of life and specific changes in bowel, urinary and sexual functions. The questionnaire was validated by a test-retest pilot study. The repeated measures analysis of variance and analysis of covariance were conducted on all outcomes measures. All statistical tests were two-sided. RESULTS: In the first month after treatment, the RP group reported a significant decrease in general HRQOL than that observed in patients receiving EBRT (p<0.00l). At 3 months of follow-up, the general HRQOL differences among the groups were less striking, and at i2 months, the scores were not statistically different from the baseline scores in both treatment groups (p=0.431). After treatment the RP group showed a significantly lower urinary function score than the EBRT group (p<0.001). Urinary function improved with time during the first year after RP but remained fairly constant during year 2. Approximately 10.6% of RP and 2.9% of EBRT patients (OR-3.9, 95% confidence interval [CI]-1.4 to 5.9) were incontinent at 2 years. The EBRT group was associated with significant worse bowel fimction than the RP group throughout follow-up time (p<0.001). Approximately 26.5% of EBRT and 6.1% of RP patients (OR=0.23, 95% CI-0.1 to 0.5) had bowel dysfunction at 2 years. Sexual function was significantly better in EBRT than RP group just after treatment (p<0.001). During follow-up, the EBRT group showed a modest but statistically significant decline in sexual function, whereas the RP group improving over time. However, at 2 years sexual dysfunction was more prevalent in the RP than in the EBRT group (70.2% versus 61.2%; OR-2.5, 95% CI=1.6 to 3.8). The bothersome scores generally correlated with the functionality scores.
CONCLUSIONS: A significant decrease in general HRQOL was evident only in the first month after RP. Patients undergoing RP report significantly worse urinary function, but better bowel function than those treated with EBRT. Both groups have a decline in sexual function throughout the post-treatment period. During the follow-up patients treated with EBRT began to show a continuing decline in erectile function.
Pi8 LOCAUSEDPROSTATECAN~ERiNONSUR6iC~~DiCALTREATMENTSII
OF RADICAL PROSTATECTOMY PROSTATE CANCER
Joniau S., Goeman L., Van Poppel H.
MATERIAL & METHODS: 106 subsequent patients with isolated HG PIN on standard octant prostate biopsies were included in the study. A total of 78 patients was further evaluated and underwent repeat biopsies at 3 months (visit 2 = V2) and 6 months (visit 3 = V3). Prostate cancer was found in 16.6% (13/78) of patients at V2, and in 19.2% (15/78) of patients at V3. Total cancer detection was 35.8%. Of the 28 patients in whom prostate cancer was detected, a radical prostatectomy was performed in 24 (11 in the V2 and 13 in the V3 group). RESULTS: In 13 patients of the V2 group and 11 patients of the V3 group, a radical prostatectomy was performed. Histopathological parameters were recorded for each group. pT2
pT3
Section
T volume] T voluJylc
Gleason
Gleason
_>Sc°re7
Visit 2 (n=13)
38.5% (n=5)
61.5% (n=8)
92.3% (n=12)
7.7% :(n=l)
15.4% (n=2)
30.8% (n=4)
69.2% (n=9)
Visit 3 (n=l 1)
90.9% (n=10)
9.1% (n=l)
100% (n=ll)
0% (n=0)
0% (n=0)
63.6% (n=7)
36.4% (n=4)
PosMargins < 0,5 ml i > 0,5 ml
C O N C L U S I O N S : Although we found similar cancer detection rates in first and second repeat biopsies following the diagnosis of isolated H G PIN in standard octant biopsies, the pathological features o f the detected tumours are quite different when assessed in radical prostatectomy specimens. It is concluded that a less aggressive approach is warranted in patients who have cancer at second (or later) repeat biopsies.
304
303
P A T I E N T S W I T H A S Y M P T O M A T I C P R O S T A T E C A N C E R T.0-4 N.0-2 M.0 NOT SUITABLE FOR LOCAL DEFINITIVE TREATMENT: DO THEY NEED IMMEDIATE ANDROGEN DEPRIVATION?
S P E C I M E N S IN
INFLUENCE OF DEFERRED TREATMENT WITH CURATIVE INTENT O N P R O G R E S S I O N F R E E S U R V I V A L R A T E S IN P R O S T A T E C A N C E R Roemeling S., De '?ties S., Gosselaar C., Schroeder F., ERSPC, Rotterdam, The Netherlands
Studer U.E?, Whelan p2, Albrecht W. 3, Casselman j.4, De Reijke T. s, Hanri D. 6, Loidl W. 7, Isorna S. s, Sundaram S.K. 9, Debois M. 1°, Collette L. 1°, EORTC Genitourinary Group ~University Hospital of Bern, Department of Urology, Bern, Switzerland, aSt. James Hospital, Department of Urology, Leeds, United Kingdom, 3Rudolfstiftung, Department of Urology, Vienna, Austria, 4Belgische Vereniging veer Urologie, Department of Urology, Oostende, Belgium, SAcademisch Medisch Centrum, Department of Urology, Amsterdam, The Netherlands, 6Universit~tsspital Z/Jrich, Department of Urology, Ztlrich, Switzerland, 7Krankenhaus Barmherzige Schwestern, Department of Urology, Linz, Austria, SHospital N.S. Del Pine, Department of Urology, Las Palmas, Spain, 9, -, Wakefield, United Kingdom, mEORTC, Data Center, Brussels, Belgium INTRODUCTION & OBJECTIVES: In patients with localized N0-2 prostate cancer EORTC trial 30891 compared prospectively immediate endocrine treatment with orchiectomy or LH-RH analog (Buserelin® 2-monthly depot) to deferred treatment initiated at the time of symptomatic disease progression or life-threatening complications. MATERIAL & METHODS: The trial aimed to demonstrate equivalent overall survival. Data from 985 patients randomized between 1990 and 1999 were used. RESULTS: Patients were 73 years old in median (52-81) and characteristics were well balanced in the two groups. After a median follow-up of 7.8 years, 541 deaths were reported. The trial failed to demonstrate equivalent survival: the 95% confidence interval for the relative increase in overall mortality with deferred treatment compared to immediate treatment ranged from +5% to +48%. The absolute increase in death rate was +7% at 5 years and +11% at 10 years. Survival was thus better on immediate treatment. The data also suggest that mortality definitively or probably due to prostate cancer was not substantially increased, irrespective whether the cause of death was assessed by the local investigator, the study coordinator or two independent reviewers (Pea mortality was 29.0% vs. 26.2% on deferred and immediate, resp.). Which competing cause of death contributed to the difference in overall survival is difficult to assess as multiple factors are often present in this old population, but no difference in cardiovascular event rate was observed. With the available follow-up data, time from entry on study to the first symptoms after onset of hormonal treatment seemed not to be influenced by treatment policy, neither was the time to appearance of first objective progression after onset of immediate or deferred hormonal treatment. In the patients who started deferred hormonal treatment, treatment was initiated in median 3.2 years after entry on study. On deferred treatment 126 patients died without needing treatmem (44% of the deceased cases, 25% of all patients). CONCLUSIONS: Overall survival was better with immediate androgen deprivation. The leading cause for this difference is unknown, however, no significant difference was found in P e a nor overall symptom free survival. The data suggest that the deferred approach may spare the burden of the treatment to a substantial number of patients.
European Urology Supplements 4 (2005) No. 3, pp. 78
Erasmus Me, Urology, Rotterdam, The Netherlands INTRODUCTION & OBJECTIVES: The optimal moment for definitive curative treatment for localized prostate cancer in men initially managed on a watchful waiting policy remains controversial. The goal of this study was to evaluate whether deferred treatment in screen detected cases leads to more biochemical progression compared to matched cases who directly received treatment with curative intent. MATERIAL & METHODS: In this case-control study, patients initially monitored on a watchful waiting policy were matched with controls who directly received treatment with curative intent. The choice of initial treatment was patient desire or physician advice. All cases were diagnosed with prostate cancer from September '94 through July '02 in the screen arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam. To every case two controls were matched for age, PSA, number of previous screen tests, biopsy Gleason score and clinical T-stage. The control cases were randomly selected. Endpoints were biochemical progression (BP) and (disease specific) mortality. BP after radical prostatectomy (RP) was defined as two consecutive PSA values of 0.2 ng/mI or higher and three consecutive PSA increases (ASTRO criteria) after radiotherapy (RT). RESULTS: Of 209 men managed on a watchful waiting policy 27 (12.9%) received deferred treatment (DT) with curative intent. Six men received a tiP and 21 RT. These cases were compared with 52 control patients, as one RT case could not be matched. Median age (range) of the RP and RT group was 69.5 years mad 67.7 years, median PSA at diagnosis 3.8 ng/ml and 4.8 ng/ml. Most cases had a Gleason score of 3 + 3 (77.0%). Except for 1 patient all men had organ confined disease on digital rectal examination, with 84.6% having T1C. Median time to DT was 8.2 (2.4-53.0) months in RP and 19.3 (12.0-58.6) months in RT. Median follow-up after DT respectively was 73.1 (47.1-85.0) and 21.0 (5.7-57.2) months. Total follow-up of the controls treated with RP or RT was 75.3 (18.9-99.5) or 40.4 (10.8-103.6) months. One case treated with deferred RP had BP while none of the RT treated cases had BP of disease. In the control group 3 (25.0%) patients had BP after RP and 2 (5%) after RT. No case in the RP group died, while one patient in the deferred RT group died. In the RP control group 2 (16.7%) patients died compared to 3 (7.5%) in the RT control group. None of these patients died of prostate cancer. CONCLUSIONS: Biochemical progression rates were not higher in patients with deferred treatment compared to those directly treated with curative intent. This descriptive study thus supports former evidence that deferring treatment in patients with selected, favourable prostate cancer characteristics does not influence the time of biochemical progression. If these preliminary results turn out to be consistent after longer follow-up, treatment related sideeffects can be postponed, resulting in increased quality of life without compromising disease specific survival.