- Email: [email protected]
Prostate brachytherapy. Complications, prognostic factors, and results
Group I: Docetaxel 75mg/sq.m Intravenously every 3rd week. Group II: Docetaxel 30mg/sq.m Intravenously weekly. Group I: 20 Patients of HRCaP between 58-82 years of age were enrolled to receive Docetaxel 75mg/sq.m. intravenously every 3rd week with a median 6 dose schedule. All patients were D-II stage disease. Median prostate specific antigen (PSA) at the time of entry was 180ng/ml and the median follow up was 28 months. Group II: 20 Patients of HRCaP between 58-78 years of age were enrolled to receive Docetaxel 30mg/sq.m. intravenously weekly with a median 30 dose schedule. All patients were D-II stage disease. Median prostate specific antigen (PSA) at the time of entry was 230 ng/ml and the median follow up was 24 months. Follow-up included serum PSA (sPSA) estimation, skeletal survey, isotope bone scan, and quality of life. Results: An objective response in PSA reduction by 80% was observed in 5 patients (25%) in group I as compared to 8 (40%) patients in group II and more than 50% reduction seen in 12 patients (60%) in group I as compared to 7 (35%) in group II. Three patients showed increase in sPSA levels as compared to 2 patients in group II. 70% of patients with symptomatic disease showed improvement on treatment regimen 1 as compared to 67.5% on treatment regimen 2. In 12 patients (60%), the disease was stable and showed response for a median period of 16 months in group I as compared to 11 patients (55%) for a median period of 12 months in group II. The median overall survival was 22 months in group I and 19 months in group II. Adverse reactions in the form of: ➢Anaemia, neutropenia, leucopenia was seen in 20 patients (100%) in group I as compared to 6 patients (30%) in group II. ➢Stomatitis, fever and alopecia are seen in 12 patients in group I however mild adverse reactions were found in group II. ➢Oral thrush was seen in 4 patients (20%) in group I as compared to 2 patients (10%) in group II. There were 5 mortalities in group I as compared to 8 mortalities in group II. Conclusions: The weekly regimen of the Docetaxel is found to be comparable in terms of efficacy however with an edge in survival benefits in group I and an advantage over 3 weekly regimen as far as the safety profile is concerned. The weekly regimen markedly decreased the use of recombinant erythropoietin and G-CSF in patients on Docetaxel, a definite advantage.
11
International study into the use of intermittent therapy in prostate cancer Shaw G1, Cotton L1, Wilson P1, Cuzick J2, Oliver RTD1 1 St Bartholomews Hospital, London, UK, 2Cancer Research, UK Introduction: PSA screening has shifted detection of prostate cancer to earlier disease. Treatment has not changed accordingly. Intermittent hormone therapy (IHT) may be useful when risk of morbidity associated with long term hormone therapy isn’t warranted and “no treatment” remains unpalatable. Stopping hormone therapy after a good response may be feasible in late disease to improve quality of life and cost of treatment. Phase three trials have established the safety of IHT in the short term when compared to continuous hormone ablation. There are significant advantages to IHT use in terms UROLOGY 66 (Supplement 3A), September 2005
of cost and quality of life. Phase 2 studies have reported various IHT protocols which will need comparison in the next generation of phase three trials. Methods: A Pubmed search was undertaken with keywords intermittent hormone/androgen ablation. 11 groups were identified with data on the use of intermittent hormone therapy in prostate cancer (n⬎50). The individual patient data was collated. Statistical analysis was undertaken using STATA intercooled v8.0. The ISICAP group met in London on 5th March 2005 to discuss preliminary analysis. Results: Data was collated for 1690 patients with adequate data on staging and previous treatment. These were subdivided into: ➢localized disease treated primarily with IHT (n⫽601) ➢local recurrence after previous radical treatment (n⫽719) ➢metastatic disease (n⫽370). Table 1.
Localized disease (nⴝ601)
Locally recurrent disease (nⴝ719)
Known nodal or metastatic disease (nⴝ349)
Overall survival at 5 years
92%
87%
69%
Percent of patients off at 2 years
53%
33%
16%
Number developing AIPC at 5 years
6%
16%
41%
Factors found to be predictive of time off, time to development of AIPC and death (at p⬍0.05 level) include age, initial and starting PSA levels, grade and stage, age, type and duration of treatment. Grade and age were not significant in the metastasis group. Indirect evidence supporting the use of duration of remission as a surrogate marker for time to AIPC and death is examined. Conclusions: This information allows rational planning of further phase three trials to evaluate the efficacy of different regimes proposed. These studies, if adequately planned, will also provide information regarding the biology of prostate cancer when treated with intermittent hormone therapy.
12
Prostate brachytherapy. Complications, prognostic factors, and results Rempelakos A1, Palanzas A1, Kritselis G2, Papas A1, Ioanidou G2, Thanos A1 1 Department of Urology, 2Department of Radiation Oncology, Saint Savas Anticancer Institute, Athens, Greece Objectives: Complications, prognostic factors and results from the first 151 cases with localized prostate cancer treated with brachytherapy are presented. Patients and Methods: During the last four years, 151 patients with localized prostate cancer were treated with brachytherapy. Permanent implantation consists of 21 to 83 I-125 seeds of 0.529 mCi each for a total implant dose of 145 Gy. Prostate size ranged from 8 to 49 cc and in 48 patients (32%) the size was more than 36 cc. The symptoms score was more than 17 in 20 patients. Hormone therapy was given in cases with prostate volume over 40 cc for three months and in high risk patients for six months. The modified peripheral loading implant was 5
used and a-blockers preimplantation, were administered to most of our patients. The follow-up ranged from 4 to 53 months (median 27.2) and consists of clinical examination and serum PSA every three months. Results: No patient was incontinent after treatment. Acute urinary retention was developed in 14 patients (9%) and in 12 of them (86%) the size of prostate was more than 35 cc and the symptom score was more than 15. During the first three months postimplantation about 53% of the patients complained of dysuria, urgency, frequency and nocturia but their urinary complaints disappeared within one year postimplantation. Six patients (4%) developed mild proctitis. From the potent patients preimplantation, 65% remained at the same condition at the end of the first year. Biochemical relapse appeared in 9(6%) of our 147 patients. Conclusions: Prostate size and symptom score are predictor factors for acute urinary retention, and prophylactic use of ␣-blockers seems to reduce the incidence of postimplantation acute retention. Hormone therapy for six or more months may protect the high risk group patients from biochemical relapse. Also, lower incidence of impotence was found. Although it is early to comment on the outcome of this method it is encouraging that only 9 patients from the intermediate and high risk group had a biochemical relapse after 21 to 54 months.
13
Iodine 125 brachytherapy for favorable risk prostate cancer: results for 509 patients. When can we start to trust PSA after brachytherapy? Crook J, Yeung I, Gillan C, McLean M, Lockwood G Princess Margaret Hospital, Toronto, Ontario, Canada Purpose: Brachytherapy is a popular and highly effective treatment option for early stage favorable prostate cancer. We describe intermediate term results in terms of efficacy and toxicity for 509 patients treated with permanent seed Iodine 125 brachytherapy. Material and Methods: Between 03/99 and 02/04 509 men were treated with Iodine 125 permanent seed brachytherapy at a single institution. Median age was 65 years (45-83). Stage was T1c in 66% and T2a in 34%. Gleason score was ⬍ 6 in 4%, 6 in 92% and 7 in 4%. Median baseline PSA was 5.6 ng/ml. Prior hormone therapy was used in 20% for the purpose of downsizing the prostate. Baseline IPS score was 5. Implants were preplanned by TRUS and performed under general anesthesia using TRUS guidance. Post-plan assessments were performed at 1 month using MR-CT fusion. Quality, toxicity, deaths and documented failures are reported for the entire population (n⫽509). To allow for resolution of benign PSA bounces in early months (defined as any rise ⬎0.2 ng/ml), PSA results are only examined beyond 30 months (n⫽259). Results: Median V100 (% of prostate volume receiving prescribed 145 Gy) is 93% and median D90 (minimum dose delivered to 90% of the prostate volume) was 154 Gy. 16% required any insertion of a catheter following the procedure. Median IPS score at 30 mo is 6 and at 60 mo is 5. Seven men (1%) developed a urethral stricture. RTOG grade 1 proctitis occurred in 3% and grade 2 in one patient. Eleven men have died, 1 from prostate cancer and 10 from other causes. There are 7 failures: 3 distant, one local and 3 biochemical. The median PSA at 30 months is 0.3 ng/ml, at 36 mo: 0.18 ng/ml, at 48 mo: 0.06 ng/ml and at 60 mo ⬍0.05 ng/ml. PSA bounce was 6
seen in 39% of patients with followup ⬎ 30 mo (excluding those with prior hormone therapy). By 30 months, 66% of bounces had resolved, while 34% were ongoing. By 36 months, 78% had resolved (n⫽59) and 22% were ongoing (n⫽17: 3 rising, 3 double bounces, 8 only one increased reading, 3 declining but not yet back to prebounce level). The median time to bounce was 15 months, mean duration 8 months. Bounces still ongoing at 36 months tended to start later (median 24 mo) but were otherwise similar in terms of peak PSA level reached. Conclusions: For favorable early stage prostate cancer, permanent seed Iodine 125 brachytherapy is well tolerated. Intermediate term results would indicate a high degree of efficacy. The majority of PSA bounces occur before 36 months but can occur later. Four to 5 years are required for PSA to reach undetectable levels and PSA is probably not a reliable indicator of failure until this time.
14
Treatment of intermediate or high-risk prostate cancer by dose escalation with HDR brachytherapy: early toxicity and biochemical outcome of two treatment regimens Guix B, Serrate R, Henrı´quez I, Bartrina JM, Vendrell JR, Tello JI Radiation Oncology Department, IMOR Foundation, Medical Insitute for Onco-Radiotherapy, Universitat de Barcelona, Spain Purpose: To report early and late toxicity and preliminary biochemical outcome in 345 patients with intermediate or high risk clinically localized prostate cancer treated with highdose-rate brachytherapy (HDRB) after 3D conformal external beam radiotherapy (3D-EBRT) to the prostate and seminal vesicles. Methods: Between 12/1999 and 10/2003, 345 patients with PSA⬎10, Gleason score⬎6 and/or T2b-T3 N0 M0 prostate cancer were treated with 3D-EBRT followed by HDR brachytherapy implant to the prostate. Patients were randomly assigned to one of the two treatment groups: 50.4 Gy to the whole pelvis and 66.6 Gy to the prostate followed by 2-3 fractions of 3.5-5 Gy in 1 insertion (group 1, 172 patients) or 50.4 Gy to whole pelvis followed by 2 fractions of 9 Gy in 1 insertion (group 2, 173 patients). Acute and late toxicities were scored by the EORTC/RTOG morbidity grading scales. Special attention was given to local, regional or distant recurrence, survival, late effects, PSA and testosterone levels and quality of life. Results: All patients completed treatment. One patient included in the group 1 and none of the group 2 experienced grade 3 rectal toxicity (rectal ulcer). Twenty-eight patients of group 1 (20.4%) and 20 patients of group 2 (11.5%). Seven patients in each group (4.0%) developed acute grade 2 urinary symptoms, and none experienced urinary retention. No patient (0%) developed grade 4 rectal complications or grade 3 or 4 urinary complications. The 4-year actuarial PSA relapsefree survival rates for intermediate and unfavourable risk group 1 patients were 92 and 91% respectively and 95 and 92% for group 2 patients. Conclusions: The data presented demonstrate the feasibility of high-dose 3D-EBRT⫹HDR brachytherapy as a safe and effective method of escalating the dose to the prostate without increasing the risk of late effects. Acute as well as late rectal and urinary complications were significantly reduced, comUROLOGY 66 (Supplement 3A), September 2005
11
International study into the use of intermittent therapy in prostate cancer Shaw G1, Cotton L1, Wilson P1, Cuzick J2, Oliver RTD1 1 St Bartholomews Hospital, London, UK, 2Cancer Research, UK Introduction: PSA screening has shifted detection of prostate cancer to earlier disease. Treatment has not changed accordingly. Intermittent hormone therapy (IHT) may be useful when risk of morbidity associated with long term hormone therapy isn’t warranted and “no treatment” remains unpalatable. Stopping hormone therapy after a good response may be feasible in late disease to improve quality of life and cost of treatment. Phase three trials have established the safety of IHT in the short term when compared to continuous hormone ablation. There are significant advantages to IHT use in terms UROLOGY 66 (Supplement 3A), September 2005
of cost and quality of life. Phase 2 studies have reported various IHT protocols which will need comparison in the next generation of phase three trials. Methods: A Pubmed search was undertaken with keywords intermittent hormone/androgen ablation. 11 groups were identified with data on the use of intermittent hormone therapy in prostate cancer (n⬎50). The individual patient data was collated. Statistical analysis was undertaken using STATA intercooled v8.0. The ISICAP group met in London on 5th March 2005 to discuss preliminary analysis. Results: Data was collated for 1690 patients with adequate data on staging and previous treatment. These were subdivided into: ➢localized disease treated primarily with IHT (n⫽601) ➢local recurrence after previous radical treatment (n⫽719) ➢metastatic disease (n⫽370). Table 1.
Localized disease (nⴝ601)
Locally recurrent disease (nⴝ719)
Known nodal or metastatic disease (nⴝ349)
Overall survival at 5 years
92%
87%
69%
Percent of patients off at 2 years
53%
33%
16%
Number developing AIPC at 5 years
6%
16%
41%
Factors found to be predictive of time off, time to development of AIPC and death (at p⬍0.05 level) include age, initial and starting PSA levels, grade and stage, age, type and duration of treatment. Grade and age were not significant in the metastasis group. Indirect evidence supporting the use of duration of remission as a surrogate marker for time to AIPC and death is examined. Conclusions: This information allows rational planning of further phase three trials to evaluate the efficacy of different regimes proposed. These studies, if adequately planned, will also provide information regarding the biology of prostate cancer when treated with intermittent hormone therapy.
12
Prostate brachytherapy. Complications, prognostic factors, and results Rempelakos A1, Palanzas A1, Kritselis G2, Papas A1, Ioanidou G2, Thanos A1 1 Department of Urology, 2Department of Radiation Oncology, Saint Savas Anticancer Institute, Athens, Greece Objectives: Complications, prognostic factors and results from the first 151 cases with localized prostate cancer treated with brachytherapy are presented. Patients and Methods: During the last four years, 151 patients with localized prostate cancer were treated with brachytherapy. Permanent implantation consists of 21 to 83 I-125 seeds of 0.529 mCi each for a total implant dose of 145 Gy. Prostate size ranged from 8 to 49 cc and in 48 patients (32%) the size was more than 36 cc. The symptoms score was more than 17 in 20 patients. Hormone therapy was given in cases with prostate volume over 40 cc for three months and in high risk patients for six months. The modified peripheral loading implant was 5
used and a-blockers preimplantation, were administered to most of our patients. The follow-up ranged from 4 to 53 months (median 27.2) and consists of clinical examination and serum PSA every three months. Results: No patient was incontinent after treatment. Acute urinary retention was developed in 14 patients (9%) and in 12 of them (86%) the size of prostate was more than 35 cc and the symptom score was more than 15. During the first three months postimplantation about 53% of the patients complained of dysuria, urgency, frequency and nocturia but their urinary complaints disappeared within one year postimplantation. Six patients (4%) developed mild proctitis. From the potent patients preimplantation, 65% remained at the same condition at the end of the first year. Biochemical relapse appeared in 9(6%) of our 147 patients. Conclusions: Prostate size and symptom score are predictor factors for acute urinary retention, and prophylactic use of ␣-blockers seems to reduce the incidence of postimplantation acute retention. Hormone therapy for six or more months may protect the high risk group patients from biochemical relapse. Also, lower incidence of impotence was found. Although it is early to comment on the outcome of this method it is encouraging that only 9 patients from the intermediate and high risk group had a biochemical relapse after 21 to 54 months.
13
Iodine 125 brachytherapy for favorable risk prostate cancer: results for 509 patients. When can we start to trust PSA after brachytherapy? Crook J, Yeung I, Gillan C, McLean M, Lockwood G Princess Margaret Hospital, Toronto, Ontario, Canada Purpose: Brachytherapy is a popular and highly effective treatment option for early stage favorable prostate cancer. We describe intermediate term results in terms of efficacy and toxicity for 509 patients treated with permanent seed Iodine 125 brachytherapy. Material and Methods: Between 03/99 and 02/04 509 men were treated with Iodine 125 permanent seed brachytherapy at a single institution. Median age was 65 years (45-83). Stage was T1c in 66% and T2a in 34%. Gleason score was ⬍ 6 in 4%, 6 in 92% and 7 in 4%. Median baseline PSA was 5.6 ng/ml. Prior hormone therapy was used in 20% for the purpose of downsizing the prostate. Baseline IPS score was 5. Implants were preplanned by TRUS and performed under general anesthesia using TRUS guidance. Post-plan assessments were performed at 1 month using MR-CT fusion. Quality, toxicity, deaths and documented failures are reported for the entire population (n⫽509). To allow for resolution of benign PSA bounces in early months (defined as any rise ⬎0.2 ng/ml), PSA results are only examined beyond 30 months (n⫽259). Results: Median V100 (% of prostate volume receiving prescribed 145 Gy) is 93% and median D90 (minimum dose delivered to 90% of the prostate volume) was 154 Gy. 16% required any insertion of a catheter following the procedure. Median IPS score at 30 mo is 6 and at 60 mo is 5. Seven men (1%) developed a urethral stricture. RTOG grade 1 proctitis occurred in 3% and grade 2 in one patient. Eleven men have died, 1 from prostate cancer and 10 from other causes. There are 7 failures: 3 distant, one local and 3 biochemical. The median PSA at 30 months is 0.3 ng/ml, at 36 mo: 0.18 ng/ml, at 48 mo: 0.06 ng/ml and at 60 mo ⬍0.05 ng/ml. PSA bounce was 6
seen in 39% of patients with followup ⬎ 30 mo (excluding those with prior hormone therapy). By 30 months, 66% of bounces had resolved, while 34% were ongoing. By 36 months, 78% had resolved (n⫽59) and 22% were ongoing (n⫽17: 3 rising, 3 double bounces, 8 only one increased reading, 3 declining but not yet back to prebounce level). The median time to bounce was 15 months, mean duration 8 months. Bounces still ongoing at 36 months tended to start later (median 24 mo) but were otherwise similar in terms of peak PSA level reached. Conclusions: For favorable early stage prostate cancer, permanent seed Iodine 125 brachytherapy is well tolerated. Intermediate term results would indicate a high degree of efficacy. The majority of PSA bounces occur before 36 months but can occur later. Four to 5 years are required for PSA to reach undetectable levels and PSA is probably not a reliable indicator of failure until this time.
14
Treatment of intermediate or high-risk prostate cancer by dose escalation with HDR brachytherapy: early toxicity and biochemical outcome of two treatment regimens Guix B, Serrate R, Henrı´quez I, Bartrina JM, Vendrell JR, Tello JI Radiation Oncology Department, IMOR Foundation, Medical Insitute for Onco-Radiotherapy, Universitat de Barcelona, Spain Purpose: To report early and late toxicity and preliminary biochemical outcome in 345 patients with intermediate or high risk clinically localized prostate cancer treated with highdose-rate brachytherapy (HDRB) after 3D conformal external beam radiotherapy (3D-EBRT) to the prostate and seminal vesicles. Methods: Between 12/1999 and 10/2003, 345 patients with PSA⬎10, Gleason score⬎6 and/or T2b-T3 N0 M0 prostate cancer were treated with 3D-EBRT followed by HDR brachytherapy implant to the prostate. Patients were randomly assigned to one of the two treatment groups: 50.4 Gy to the whole pelvis and 66.6 Gy to the prostate followed by 2-3 fractions of 3.5-5 Gy in 1 insertion (group 1, 172 patients) or 50.4 Gy to whole pelvis followed by 2 fractions of 9 Gy in 1 insertion (group 2, 173 patients). Acute and late toxicities were scored by the EORTC/RTOG morbidity grading scales. Special attention was given to local, regional or distant recurrence, survival, late effects, PSA and testosterone levels and quality of life. Results: All patients completed treatment. One patient included in the group 1 and none of the group 2 experienced grade 3 rectal toxicity (rectal ulcer). Twenty-eight patients of group 1 (20.4%) and 20 patients of group 2 (11.5%). Seven patients in each group (4.0%) developed acute grade 2 urinary symptoms, and none experienced urinary retention. No patient (0%) developed grade 4 rectal complications or grade 3 or 4 urinary complications. The 4-year actuarial PSA relapsefree survival rates for intermediate and unfavourable risk group 1 patients were 92 and 91% respectively and 95 and 92% for group 2 patients. Conclusions: The data presented demonstrate the feasibility of high-dose 3D-EBRT⫹HDR brachytherapy as a safe and effective method of escalating the dose to the prostate without increasing the risk of late effects. Acute as well as late rectal and urinary complications were significantly reduced, comUROLOGY 66 (Supplement 3A), September 2005