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METASTATIC DISEASE RATES AFTER RADICAL PROSTATECTOMY AND RADIOTHERAPY IN SCREEN-DETECTED PROSTATE CANCER
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POOR OVERALL SURVIVAL IN MEN TREATED WITH DEFINITIVE RADIOTHERAPY WITHOUT EVIDENCE OF DISEASE RELAPSE – ARE WE TREATING TOO MANY MEN WITH RADIOTHERAPY?
NON-METASTATIC HORMONE-REFRACTORY PROSTATE CANCER (HRPC): IS ANY PLACE FOR CONFORMAL RADIOTHERAPY IN MANAGEMENT?
Stikarovska I., Perrotte P., Saad F., Mccormack M., Karakiewicz P.I.
Milecki P.1, Milecki P.1, Martenka P.1, Kwias Z.2, Antczak A.2
University of Montreal, Cancer Prognostics and Outcomes Research Unit, Montreal, Canada
1
INTRODUCTION & OBJECTIVES: Short survival after definitive therapy, without evidence of disease relapse may suggest treatment of individuals whose life expectancy does not warrant definitive therapy. We examined survival after definitive radiotherapy, in men who did not receive salvage or systemic therapy after external beam radiotherapy. MATERIAL & METHODS: The RAMQ database allowed us to identify 3176 men without evidence of radiotherapy failure. We used Kaplan-Meier and Cox regression analyses to assessed survival rates. RESULTS: Follow-up time ranged from 0.1 to 185.9 months. of 3176, 1972 died (62.1%) during follow-up. Median survival time was 56.6 months (mean 76.8). Five year actuarial survival was 48.8% (47.0-50.5%), 10 year survival was 30.4% (28.4-32.5%) and 15 year survival was 17.9% (14.6-21.6%). Overall survival is shown in Figure 1 and temporal trends in 48 month survival are shown in Figure 2.
Great Poland Cancer Centre, Radiotherapy, Poznan, Poland, 2University School of Medical Sciences, Urology, Poznan, Poland INTRODUCTION & OBJECTIVES: Patients with diagnosis of hormone refractory prostate cancer (HRPC) present heterogeneous population and therefore, it has been proposed to subcategorize them into two subgroups depending on presence or absence of distant metastases. While the former subgroup has been typically treated with palliative intention, for the latter apparently there is no standard approach. Thus, the purpose of this work is to analyze the results of treatment of nonmetastatic HRPC with 3D-CRT and to investigate the potential prognostic factors. MATERIAL & METHODS: Of 425 patients with diagnosis of localised and locally advanced prostate cancer who were treated between 1997 and 2004 in our centre, forty-four patients were referred as to non-metastatic HRPC. Distant metastases were excluded by bone scan, chest X-ray and pelvic CT. The median pre-hormonotherapy PSA (pre-HT PSA) level for this group was 25 ng/ml (range; from 1 to 201) and 5.7 ng/ml (range; 0.06 to 27) at the beginning of radiotherapy (pre-RT PSA). Clinical T stage defined according to the 2002 AJCC, was as following: T1c =12, T2 =23, and T3 =9 patients. of 44 patient’s 39 had a Gleason score of 2-7 and 5 had a Gleason score of 8-10. All patients were treated with 3D-CRT with fraction dose of 2 Gy to total dose of 68Gy (range; 60 to 74 Gy). The median duration of androgen deprevation therapy before RT was 26 months (range; 7 to 96). The median time of follow-up was 27 months (range; from 13 to 62) and from the beginning of androgen ablation was 53 months (range; 20 to 158). The following prognostic factors were evaluated in univariate and multivariate analysis: age, pre-HT PSA, pre-RT PSA, Gleason score, total dose, PSA doubling time (PSADT< 6 months vs. PSADT > 6 months). RESULTS: The 5-year actuarial overall survival was 82% and 5-year clinical relapse free-survival rate was 49%. During the follow-up 15 patients developed clinical relapse (locoregional and/or distant and/or biochemical) and two patients died of prostate cancer. The univariate analysis indicated that preHT PSA > 20 ng/ml, pre-RT PSA > 4ng/ml, the high-risk group defined according to NCCN criteria (PSA >20 ng/ml and Gleason score >7), and Gleason score > 7 were statistically significant factors for the risk of clinical relapse. Multivariate analysis (Cox proportional hazard models) indicated that only the high-risk group (pre-HT PSA >20 ng/ml + Gleason score > 8) was an independent prognostic factor for relapse after radiotherapy.
CONCLUSIONS: Our data indicate that the selection criteria of RP candidates have worsened over time and have resulted in inclusion of men with suboptimal life expectancy to warrant definitive therapy.
CONCLUSIONS: Radiotherapy for patients with non-metastatic HRPC is valuable method of treatment in terms of relapse-free survival to the subgroup of patients with pre-HT PSA<20 ng/ml and Gleason score < 8. For patients referred as to high risk group according to NCCN criteria 3DCRT seems to be an ineffective treatment, and for this subgroup systemic modality of treatment (chemotherapy or biological manipulation) should be considered.
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728
METASTATIC DISEASE RATES AFTER RADICAL PROSTATECTOMY AND RADIOTHERAPY IN SCREEN-DETECTED PROSTATE CANCER
RADICAL RETROPUBIC PROSTATECTOMY VERSUS EXTERNAL BEAM RADIOTHERAPY FOR LOCALISED PROSTATE CANCER: AN INTERIM REPORT OF A MULTICENTRE, PROSPECTIVE, PHASE III RANDOMISED STUDY
Roemeling S.1, Roobol M.J.1, Gosselaar C.1, Franken-Raab C.G.A.M.1, Van der Kwast T.H.2, Schröder F.H.1 1
Erasmus Mc University Medical Centre, Department of Urology, Rotterdam, The Netherlands, Mount Sinai Hospital, Department of Pathology and Laboratory Medicine, Toronto, Canada
2
INTRODUCTION & OBJECTIVES: The preferred treatment of patients with screendetected prostate cancer (PC) remains controversial. The choice for radical prostatectomy (RP) or radiotherapy (RT) should be dependent on demographic and clinical factors, as well as on the treatment-associated morbidity. The choice of treatment also involves consideration of efficacy in preventing metastatic disease. There are limited data assessing the relative effectiveness of different treatments among a cohort of patients with screen-detected PC. In this study, we compared the cumulative incidence rates of metastatic disease in patients with screen-detected disease who elected for RP or RT. MATERIAL & METHODS: From November 1993 through December 2003, 1,079 out of 13,711 randomised men (November 1993-January 1998) were diagnosed with PC through screening in the Rotterdam section of the European Randomised study of Screening for PC (ERSPC). RP (N=383) or RT (N=505) was performed in 888 men (82.3%), with a follow-up completed through 2004. The analysis with a Cox proportional hazards model was based on an intention to treat basis and adjusted for clinical stage, Gleason score, preoperative PSAlevel, age at time of diagnosis, screening round and treatment year. Metastatic disease was the primary endpoint, which had to be evidenced by a bonescan and adjuvant diagnostics if necessary. RESULTS: The median age at diagnosis was 64.0 years for RP (mean 63.8; range 55.0-73.9) and 68.7 years for RT (mean 67.8; range 55.6-75.6; not significant (n.s.)). Respectively 26.7% and 37.1% had a Gleason score of 7 or more (p-value=0.001). The median PSA level was 4.8 ng/mL (mean 6.0; range 0.6-33.5) for RP and 5.2 ng/mL (mean 10.2; range 0.3-259.8; P-value=0.001) for RT, and digital rectal examination most frequently revealed clinical stage T2 disease in RP (200, 52.2%) as well as in RT (189, 37.4%; P-value=0.001). During a median follow-up of 6.2 years in patients who remained alive, 6 men (1.6%) who elected RP and 28 men (5.5%) who elected RT developed metastatic disease. The difference in the cumulative incidence of metastatic disease increased from 2.8 percentage points after 5 years to 6.8 percentage points after 8 years (P<0.001, log-rank test). Cox proportional hazards models produced a hazard ratio of 2.45 (95%CI 1.64-3.65) for RT compared with RP. CONCLUSIONS: In this study, metastatic disease occurred significantly less frequently in RP than in RT, and the lower cumulative incidence of metastatic disease was maintained after correction for prognostic factors. The comparison made may be skewed because the therapy of choice may be biased by these prognostic factors itself. It could be that long-term follow-up will lead to different conclusions. Therefore, further follow-up of this cohort is warranted.
Eur Urol Suppl 2006;5(2):204
Di Stasi S.M.1, Giannantoni A.2, Virgili G.1, Storti L.3, Attisani F.1, De Carolis A.1, Zampa G.4, Jannini E.A.5, Valenti M.6, Vespasiani G.1 Tor Vergata University, Department of Urology, Rome, Italy, 2University of Perugia, Department of Urology, Perugia, Italy, 3Policlinico Casilino, Operative Unit of Urology, Rome, Italy, 4San Giacomo Hospital, Operative Unit of Oncology, Rome, Italy, 5University of l’Aquila, Department of Experimenta Medicine, l’Aquila, Italy, 6University of l’Aquila, Section of Medical Statistics and Epidemiology, l’Aquila, Italy
1
INTRODUCTION & OBJECTIVES: We report the results of an interim analysis of a multicentre, prospective randomised trial comparing radical retropubic prostatectomy (RP) with conventional external beam radiotherapy (EBRT) in patients with clinically localised prostate cancer. MATERIAL & METHODS: Between January 1997 and September 2001, 137 patients with clinically localised newly diagnosed prostate cancer were randomly assigned to RP (n=70) or EBRT (n=67). Participants were excluded if they have received prior therapy for prostate cancer or are judged not to be candidates for RP. Data collected at follow-up included evidence of clinical disease progression, survival rates and general and disease specific health-related quality of life. All data were measured by physical examination, digital rectal examination, PSA, annual TC and bone scan and questionnaire. Analysis was by intention to treat. RESULTS: After a median follow-up of 67 months (range 24-88) 35 patients (32.8%) had evidence of biochemical disease progression, 22 (31.4%) in RP group and 23 (32.8%) in EBRT group respectively. The median time to biochemical failure was 55.5 months (range 1-86) in RP group and 56 (range 388) in EBRT group. A local progression was observed in 11 patients (15.79%) of RP group and 12 (17.9%) of EBRT group. The median time to local progression was 65 months (range 6-86) in RP group and 64 (range 6-88) in EBRT group. Distant metastases were observed in 4 patients (5.7%) in RP group and 6 (8.9%) in EBRT group. The median time to distant failure was 67 months (range 12-86) in RP group and 66 (range 12-88) in EBRT group. Death due to prostate cancer occurred in 3/70 of patients assigned to RP (4.3%) and in 1/67 of those assigned to EBRT (1.5%). Death due to other causes occurred in 1/70 patients in the RP group (1.4%) and in 4/ 67 patients in the EBRT group (6.0%). In EBRT group, six to twelve prostate biopsies performed 24 months after the end of treatment showed residual disease in 19 patients (28.3%) A significant decrease in general HRQOL was evident only in the first month after RP (p<0.001). Patients undergoing RP report significantly worse urinary function (p<0.001), but better bowel function than those treated with EBRT (p<0.001). Sexual dysfunction was more prevalent in the RP than in the EBRT group (70.2% versus 61.2%). CONCLUSIONS: This interim analysis indicates that there was no significant difference between RP and EBRT in terms of clinical disease progression and survival rates in patients with clinically localised prostate cancer. A 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. However, additional larger sample size accrual and long-term follow-up data are warranted to confirm these results.
726
POOR OVERALL SURVIVAL IN MEN TREATED WITH DEFINITIVE RADIOTHERAPY WITHOUT EVIDENCE OF DISEASE RELAPSE – ARE WE TREATING TOO MANY MEN WITH RADIOTHERAPY?
NON-METASTATIC HORMONE-REFRACTORY PROSTATE CANCER (HRPC): IS ANY PLACE FOR CONFORMAL RADIOTHERAPY IN MANAGEMENT?
Stikarovska I., Perrotte P., Saad F., Mccormack M., Karakiewicz P.I.
Milecki P.1, Milecki P.1, Martenka P.1, Kwias Z.2, Antczak A.2
University of Montreal, Cancer Prognostics and Outcomes Research Unit, Montreal, Canada
1
INTRODUCTION & OBJECTIVES: Short survival after definitive therapy, without evidence of disease relapse may suggest treatment of individuals whose life expectancy does not warrant definitive therapy. We examined survival after definitive radiotherapy, in men who did not receive salvage or systemic therapy after external beam radiotherapy. MATERIAL & METHODS: The RAMQ database allowed us to identify 3176 men without evidence of radiotherapy failure. We used Kaplan-Meier and Cox regression analyses to assessed survival rates. RESULTS: Follow-up time ranged from 0.1 to 185.9 months. of 3176, 1972 died (62.1%) during follow-up. Median survival time was 56.6 months (mean 76.8). Five year actuarial survival was 48.8% (47.0-50.5%), 10 year survival was 30.4% (28.4-32.5%) and 15 year survival was 17.9% (14.6-21.6%). Overall survival is shown in Figure 1 and temporal trends in 48 month survival are shown in Figure 2.
Great Poland Cancer Centre, Radiotherapy, Poznan, Poland, 2University School of Medical Sciences, Urology, Poznan, Poland INTRODUCTION & OBJECTIVES: Patients with diagnosis of hormone refractory prostate cancer (HRPC) present heterogeneous population and therefore, it has been proposed to subcategorize them into two subgroups depending on presence or absence of distant metastases. While the former subgroup has been typically treated with palliative intention, for the latter apparently there is no standard approach. Thus, the purpose of this work is to analyze the results of treatment of nonmetastatic HRPC with 3D-CRT and to investigate the potential prognostic factors. MATERIAL & METHODS: Of 425 patients with diagnosis of localised and locally advanced prostate cancer who were treated between 1997 and 2004 in our centre, forty-four patients were referred as to non-metastatic HRPC. Distant metastases were excluded by bone scan, chest X-ray and pelvic CT. The median pre-hormonotherapy PSA (pre-HT PSA) level for this group was 25 ng/ml (range; from 1 to 201) and 5.7 ng/ml (range; 0.06 to 27) at the beginning of radiotherapy (pre-RT PSA). Clinical T stage defined according to the 2002 AJCC, was as following: T1c =12, T2 =23, and T3 =9 patients. of 44 patient’s 39 had a Gleason score of 2-7 and 5 had a Gleason score of 8-10. All patients were treated with 3D-CRT with fraction dose of 2 Gy to total dose of 68Gy (range; 60 to 74 Gy). The median duration of androgen deprevation therapy before RT was 26 months (range; 7 to 96). The median time of follow-up was 27 months (range; from 13 to 62) and from the beginning of androgen ablation was 53 months (range; 20 to 158). The following prognostic factors were evaluated in univariate and multivariate analysis: age, pre-HT PSA, pre-RT PSA, Gleason score, total dose, PSA doubling time (PSADT< 6 months vs. PSADT > 6 months). RESULTS: The 5-year actuarial overall survival was 82% and 5-year clinical relapse free-survival rate was 49%. During the follow-up 15 patients developed clinical relapse (locoregional and/or distant and/or biochemical) and two patients died of prostate cancer. The univariate analysis indicated that preHT PSA > 20 ng/ml, pre-RT PSA > 4ng/ml, the high-risk group defined according to NCCN criteria (PSA >20 ng/ml and Gleason score >7), and Gleason score > 7 were statistically significant factors for the risk of clinical relapse. Multivariate analysis (Cox proportional hazard models) indicated that only the high-risk group (pre-HT PSA >20 ng/ml + Gleason score > 8) was an independent prognostic factor for relapse after radiotherapy.
CONCLUSIONS: Our data indicate that the selection criteria of RP candidates have worsened over time and have resulted in inclusion of men with suboptimal life expectancy to warrant definitive therapy.
CONCLUSIONS: Radiotherapy for patients with non-metastatic HRPC is valuable method of treatment in terms of relapse-free survival to the subgroup of patients with pre-HT PSA<20 ng/ml and Gleason score < 8. For patients referred as to high risk group according to NCCN criteria 3DCRT seems to be an ineffective treatment, and for this subgroup systemic modality of treatment (chemotherapy or biological manipulation) should be considered.
727
728
METASTATIC DISEASE RATES AFTER RADICAL PROSTATECTOMY AND RADIOTHERAPY IN SCREEN-DETECTED PROSTATE CANCER
RADICAL RETROPUBIC PROSTATECTOMY VERSUS EXTERNAL BEAM RADIOTHERAPY FOR LOCALISED PROSTATE CANCER: AN INTERIM REPORT OF A MULTICENTRE, PROSPECTIVE, PHASE III RANDOMISED STUDY
Roemeling S.1, Roobol M.J.1, Gosselaar C.1, Franken-Raab C.G.A.M.1, Van der Kwast T.H.2, Schröder F.H.1 1
Erasmus Mc University Medical Centre, Department of Urology, Rotterdam, The Netherlands, Mount Sinai Hospital, Department of Pathology and Laboratory Medicine, Toronto, Canada
2
INTRODUCTION & OBJECTIVES: The preferred treatment of patients with screendetected prostate cancer (PC) remains controversial. The choice for radical prostatectomy (RP) or radiotherapy (RT) should be dependent on demographic and clinical factors, as well as on the treatment-associated morbidity. The choice of treatment also involves consideration of efficacy in preventing metastatic disease. There are limited data assessing the relative effectiveness of different treatments among a cohort of patients with screen-detected PC. In this study, we compared the cumulative incidence rates of metastatic disease in patients with screen-detected disease who elected for RP or RT. MATERIAL & METHODS: From November 1993 through December 2003, 1,079 out of 13,711 randomised men (November 1993-January 1998) were diagnosed with PC through screening in the Rotterdam section of the European Randomised study of Screening for PC (ERSPC). RP (N=383) or RT (N=505) was performed in 888 men (82.3%), with a follow-up completed through 2004. The analysis with a Cox proportional hazards model was based on an intention to treat basis and adjusted for clinical stage, Gleason score, preoperative PSAlevel, age at time of diagnosis, screening round and treatment year. Metastatic disease was the primary endpoint, which had to be evidenced by a bonescan and adjuvant diagnostics if necessary. RESULTS: The median age at diagnosis was 64.0 years for RP (mean 63.8; range 55.0-73.9) and 68.7 years for RT (mean 67.8; range 55.6-75.6; not significant (n.s.)). Respectively 26.7% and 37.1% had a Gleason score of 7 or more (p-value=0.001). The median PSA level was 4.8 ng/mL (mean 6.0; range 0.6-33.5) for RP and 5.2 ng/mL (mean 10.2; range 0.3-259.8; P-value=0.001) for RT, and digital rectal examination most frequently revealed clinical stage T2 disease in RP (200, 52.2%) as well as in RT (189, 37.4%; P-value=0.001). During a median follow-up of 6.2 years in patients who remained alive, 6 men (1.6%) who elected RP and 28 men (5.5%) who elected RT developed metastatic disease. The difference in the cumulative incidence of metastatic disease increased from 2.8 percentage points after 5 years to 6.8 percentage points after 8 years (P<0.001, log-rank test). Cox proportional hazards models produced a hazard ratio of 2.45 (95%CI 1.64-3.65) for RT compared with RP. CONCLUSIONS: In this study, metastatic disease occurred significantly less frequently in RP than in RT, and the lower cumulative incidence of metastatic disease was maintained after correction for prognostic factors. The comparison made may be skewed because the therapy of choice may be biased by these prognostic factors itself. It could be that long-term follow-up will lead to different conclusions. Therefore, further follow-up of this cohort is warranted.
Eur Urol Suppl 2006;5(2):204
Di Stasi S.M.1, Giannantoni A.2, Virgili G.1, Storti L.3, Attisani F.1, De Carolis A.1, Zampa G.4, Jannini E.A.5, Valenti M.6, Vespasiani G.1 Tor Vergata University, Department of Urology, Rome, Italy, 2University of Perugia, Department of Urology, Perugia, Italy, 3Policlinico Casilino, Operative Unit of Urology, Rome, Italy, 4San Giacomo Hospital, Operative Unit of Oncology, Rome, Italy, 5University of l’Aquila, Department of Experimenta Medicine, l’Aquila, Italy, 6University of l’Aquila, Section of Medical Statistics and Epidemiology, l’Aquila, Italy
1
INTRODUCTION & OBJECTIVES: We report the results of an interim analysis of a multicentre, prospective randomised trial comparing radical retropubic prostatectomy (RP) with conventional external beam radiotherapy (EBRT) in patients with clinically localised prostate cancer. MATERIAL & METHODS: Between January 1997 and September 2001, 137 patients with clinically localised newly diagnosed prostate cancer were randomly assigned to RP (n=70) or EBRT (n=67). Participants were excluded if they have received prior therapy for prostate cancer or are judged not to be candidates for RP. Data collected at follow-up included evidence of clinical disease progression, survival rates and general and disease specific health-related quality of life. All data were measured by physical examination, digital rectal examination, PSA, annual TC and bone scan and questionnaire. Analysis was by intention to treat. RESULTS: After a median follow-up of 67 months (range 24-88) 35 patients (32.8%) had evidence of biochemical disease progression, 22 (31.4%) in RP group and 23 (32.8%) in EBRT group respectively. The median time to biochemical failure was 55.5 months (range 1-86) in RP group and 56 (range 388) in EBRT group. A local progression was observed in 11 patients (15.79%) of RP group and 12 (17.9%) of EBRT group. The median time to local progression was 65 months (range 6-86) in RP group and 64 (range 6-88) in EBRT group. Distant metastases were observed in 4 patients (5.7%) in RP group and 6 (8.9%) in EBRT group. The median time to distant failure was 67 months (range 12-86) in RP group and 66 (range 12-88) in EBRT group. Death due to prostate cancer occurred in 3/70 of patients assigned to RP (4.3%) and in 1/67 of those assigned to EBRT (1.5%). Death due to other causes occurred in 1/70 patients in the RP group (1.4%) and in 4/ 67 patients in the EBRT group (6.0%). In EBRT group, six to twelve prostate biopsies performed 24 months after the end of treatment showed residual disease in 19 patients (28.3%) A significant decrease in general HRQOL was evident only in the first month after RP (p<0.001). Patients undergoing RP report significantly worse urinary function (p<0.001), but better bowel function than those treated with EBRT (p<0.001). Sexual dysfunction was more prevalent in the RP than in the EBRT group (70.2% versus 61.2%). CONCLUSIONS: This interim analysis indicates that there was no significant difference between RP and EBRT in terms of clinical disease progression and survival rates in patients with clinically localised prostate cancer. A 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. However, additional larger sample size accrual and long-term follow-up data are warranted to confirm these results.