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Summary of simultaneous irradiation for prostate cancer
EDITORIAL
SUMMARY OF SIMULTANEOUS IRRADIATION FOR PROSTATE CANCER FRANK A. CRITZ
A
fter our negative experience with retropubic iodine-125 implantation alone for prostate cancer, external beam radiotherapy was added after the implantation. A formal study of this treatment process was started in January 1984. Because the prostate is irradiated at the same time owing to performing an iodine-125 implant first followed by external beam radiotherapy, this method was called simultaneous irradiation (SI). A change from the retropubic to the modern ultrasound-guided transperineal implant technique as a part of SI was begun in 1992. This report summarizes the experience of this facility with SI, with the focus almost exclusively on men implanted by the transperineal technique. MATERIAL AND METHODS
Three databases were evaluated. Database 1 consisted of 5509 consecutive men with clinical Stage T1-T4NxM0 prostate cancer treated with SI using the transperineal implant technique from August 1992 to August 2002. All these men had been treated 18 or more months previously. This database was used to evaluate the treatment-related morbidity, and data were gathered through post-treatment questionnaires either mailed to men or given at each clinic follow-up visit. Database 2 was a subset of database 1 and consisted of 1658 consecutive men with Stage T1-T2NxM0 cancer and 74 consecutive men with Stage T3-T4NxM0 prostate cancer treated 5 or more years previously (August 1992 to December 1998). None of these men had received neoadjuvant androgen deprivation. This database was used to evaluate freedom from disease. The median pretreatment prostate-specific antigen (PSA) level for men with Stage T1-T2 was 7.1 ng/mL (range 0.3 to 88), and 75% had a Gleason score of 6 or less on prostate biopsy taken from unreviewed community hospital pathology reports. A median dose of 11,500 cGy calculated at the prostatic capsule was delivered by the implant using the urethralsparing technique plus implantation of the seminal vesicles. Three weeks after implantation, external beam radiotherapy was delivered to the prostate, periprostatic tissues, and seminal vesicles at a daily dose rate of 150 cGy, 5 days/wk, to a total dose of 4500 cGy. Men with a pretreatment PSA level of 10.1 ng/mL or greater, Gleason score of 7 or greater, or prostatic base involvement either by palpation or biopsy were given an additional 750-cGy boost to the base and seminal vesicles. From the Radiotherapy Clinics of Georgia, Decatur, Georgia Reprint requests: Frank A. Critz, M.D., Radiotherapy Clinics of Georgia, 2349 Lawrenceville Highway, Decatur, GA 30033 Submitted: March 25, 2004, accepted (with revisions): June 17, 2004 © 2004 ELSEVIER INC. ALL RIGHTS RESERVED
Database 3 consisted of 359 consecutive men with clinical Stage T1-T2N0M0 prostate cancer treated with SI but implanted by the obsolete retropubic implant technique between 1984 and 1995. Follow-up examinations for all men in this study were performed every 6 months. The median follow-up for database 2 was 6 years (range 3 months to 11 years). Freedom from disease was defined by a PSA cutpoint of 0.2 ng/mL, and recurrence was defined by failure to achieve a PSA level of 0.2 ng/mL or a subsequent rise to greater than this level. Disease-free survival rates were calculated by the KaplanMeier method.
RESULTS The 10-year disease-free survival rate for the contemporary series of men with clinical Stage T1-T2 disease treated since 1992 with SI using the transperineal implant technique was 83% (Fig. 1). Of the 1658 men, 236 developed recurrence at a median of 25 months (range 3 months to 8 years) after implantation. The 10-year and 15-year disease-free survival rate was 55% and 51%, respectively, for the 359 men from database 3, who had been treated with SI but implanted using the obsolete retropubic implant technique. The 10year and 15-year disease-free survival rate was 76% and 71%, respectively, for the combined series of men implanted using either the transperineal or retropubic implant technique (Fig. 1). The median time to recurrence was 30 months (range 3 months to 13.5 years) for the total group. The 5-year disease-free survival rate was 41% for men with Stage T3-T4 disease treated since 1992 with the transperineal implant method. The frequency of invasive procedures used for the management of treatment-related morbidity was documented for all 5509 men treated with SI using the transperineal approach (Table I). Because of the impact on urinary morbidity, men were subdivided according to whether they had undergone transurethral resection of the prostate (TURP) either before or after SI. COMMENT By performing radioactive iodine-125 implantation initially, which has a 60-day half-life, followed 21 days later by external beam radiotherapy given UROLOGY 64: 633– 636, 2004 • 0090-4295/04/$30.00 doi:10.1016/j.urology.2004.06.047 633
FIGURE 1. Disease-free survival rate for contemporary series of 1658 men with clinical Stage T1-T2 treated with SI using transperineal implant technique since 1992. Second disease-free survival curve combined men with Stage T1-T2 implanted by obsolete retropubic implant technique with contemporary series documenting 15-year diseasefree survival rate after SI. Number of men at risk at 5 years of follow-up was 1255 and 1489 for transperineal and combined men, respectively, and was 17 men at 15 years of follow-up.
TABLE I. Frequency of postimplant invasive procedures for complications of simultaneous irradiation No TURP Before SI Procedure
No TURP
Patient total (n) 5106 (93) Urinary (n) Postimplant catheter 316 (6.1) Cauterization 25 (0.5) Urethral stone removal 1 (0.02) Artificial sphincter 0 Urethral dilation 57 (1.1) Urethral incision 26 (0.5) Urinary diversion 0 Rectal (n) Cauterization — Colostomy —
TURP After SI 57 (1) — 0 7 (12.2) 2 (3.5) 13 (22.8) 9 (15.8) 2 (3.5) — —
TURP Before SI 346 (6) 10 (2.9) 15 (4.3) 10 (2.9) 4 (1.2) 17 (4.9) 8 (2.3) 0 — —
All 5509 (100) 326 (5.9) 40 (0.7) 18 (0.3) 6 (0.1) 87 (1.6) 43 (0.8) 2 (0.04) 62 (1.1) 7 (0.13)
KEY: TURP ⫽ transurethral resection of prostate; SI ⫽ simultaneous irradiation. Numbers in parentheses are percentages.
within 6 to 7 weeks, the radiation dose was intensified for benign and intraprostatic malignant epithelium. The external beam component also irradiated localized extracapsular disease. The theory of SI was supported by the 10-year disease-free survival rate of 83% for men with clinical Stage T1-T2 implanted using the transperineal technique in the PSA era (Fig. 1). These results are comparable to those after radical prostatectomy, the reference standard for the treatment of prostate cancer.1 Additionally, the 15-year disease-free survival rate of 71% calculated for the combined men implanted since 1984 was compara634
ble to the 66% 15-year disease-free survival rate of men treated with radical prostatectomy at Johns Hopkins University since 1982.2 However, a comparison of the outcome of radiotherapy with radical prostatectomy may be misleading, unless two issues are addressed, the definition of freedom from disease and the minimal length of follow-up. Freedom from disease in this study was defined by a PSA cutpoint of 0.2 ng/mL, the same definition used for surgery at Johns Hopkins.1,2 Additionally, all men analyzed for freedom from disease in this report had been treated 5 or more UROLOGY 64 (4), 2004
years previously. Investigators have documented that the outcome of men treated with radiotherapy is significantly lower for men with long, compared with short, follow-up.3,4 The length of follow-up may be related to the inherent difference in the time to achieve a PSA level of 0.2 ng/mL after radiotherapy compared with after radical prostatectomy. For those men who achieve a PSA nadir of 0.2 ng/mL, no more than 1 month of follow-up is required after radical prostatectomy. In contrast, 5 years of follow-up is required for the 99th percentile of men to reach a PSA nadir of 0.2 ng/mL after SI.5 A slowly falling PSA level after radiotherapy, especially if men have a PSA “bounce,” could mask an early recurrence that otherwise would be detectable with longer follow-up. Using the format described by Sarosdy,6 the treatment-related morbidity caused by SI for men implanted using the transperineal implant technique was analyzed according to the frequency of invasive procedures for the management of complications (Table I). Postimplant catheterization for urinary retention was the most common procedure after SI. Of the 5.9% of men who were catheterized after implantation, 79% were catheterized within 1 day of the implant, and the median duration of catheter use was 7 days. The median prostate volume at implantation was 35 cm3 (range 13 to 160). The catheterization rate was 4.6% for the 5119 men with a prostate size of 60 cm3 or less. Procedures for urinary morbidity are rare, overall, and are usually related to men who have undergone TURP, especially post-treatment TURP. Overall, 67 men (1.2% of the total 5509) had undergone TURP after SI, including 10 men who had undergone preimplant TURP. For example, the incidence of stone removal from the urethra was 2.9% for men who had undergone preimplant TURP and 12.3% for men who had undergone postimplant TURP, but only 0.02% for men who had never undergone TURP. Urethral dilation or incision, usually for urethral strictures, was much more common in men who had undergone either preimplant or postimplant TURP. Procedures for rectal complications were rare. Of the 7 men who had undergone colostomy for rectoprostatic fistula, 5 had undergone rectal procedures after SI but before the development of a fistula, including 3 who had undergone rectal biopsy, which has been associated with this complication,7 1 who had required cauterization, and 1 who had undergone internal hemorrhoidectomy. Prostate iodine-125 implantation followed by external beam radiotherapy has been associated with a high rate of severe complications. The rate of colostomies for rectal fistulas has ranged from 2.8% to 6%.8,9 Sarosdy6 reported on 158 men treated with palladium implants alone or comUROLOGY 64 (4), 2004
bined with external beam radiotherapy and noted that overall 20% had required a catheter after implantation, 9% had undergone postimplant TURP, and 2.6% had undergone colostomy. Complications were substantially greater for men who had undergone combined radiotherapy. Other investigators who have treated large series of men have reported urinary retention rates of 4% to 7%, postimplant TURP rates of up to 4.7%, and urinary or rectal diversion rates of 0.33% to 1.5% after seeds alone or preceded by external beam radiotherapy.10 –13 The relatively low rate of complications in this study may have been a result of several factors, including implantation of gold seeds along with the iodine seeds as a marker for postimplant radiotherapy, daily x-rays before external beam radiotherapy for verification of patient setup, a change in beam technique on the basis of patient symptoms while undergoing external beam radiotherapy, and slower than usual fractionation of the external beam because the men were receiving simultaneous treatment from the seeds. An additional factor may have been the extensive experience with SI at this facility, similar to the finding that a high surgical volume is inversely related to in-hospital complications14 and positive surgical margins.15 CONCLUSIONS In experienced hands, integration of prostate iodine-125 implantation with subsequent external beam radiotherapy produces excellent outcomes for the treatment of prostate cancer. The diseasefree survival rates after SI calculated with an undetectable PSA in men with long follow-up were comparable to those after radical prostatectomy. Treatment-related morbidity, based on an evaluation of procedures for complications, was substantially less than that reported by other investigators using combination radiotherapy and appeared similar to that after monotherapy with seed implantation. REFERENCES 1. Han M, Partin AW, Piantadosi S, et al: Era specific biochemical recurrence-free survival following radical prostatectomy for clinically localized prostate cancer. J Urol 166: 416 – 419, 2001. 2. Han M, Partin AW, Pound CR, et al: Long-term biochemical disease-free and cancer-specific survival following anatomic radical retropubic prostatectomy. Urol Clin North Am 28: 555–565, 2001. 3. Vicini FA, Kestin LL, and Martinez AA: The importance of adequate followup in defining treatment success after external beam irradiation for prostate cancer. Int J Radiat Oncol Biol Phys 45: 553–561, 1999. 4. Connell PP, Ignacia L, McBride RB, et al: Caution in interpreting biochemical control rates after treatment for pros635
tate cancer: length of followup influences results. Urology 54: 875– 879, 1999. 5. Critz FA: Time to achieve a prostate specific antigen nadir of 0.2 ng/ml after simultaneous irradiation for prostate cancer. J Urol 168: 2434 –2438, 2002. 6. Sarosdy MF: Urinary and rectal complications of contemporary prostate brachytherapy (PB) for prostate cancer (PC)(abstract). J Urol 169: 491– 492, 2003. 7. Theodorescu D, Gillenwater JY, and Koutrouvelis PG: Prostatourethral-rectal fistula after prostate brachytherapy. Cancer 89: 2085–2091, 2000. 8. Zeitlin SI, Sherman J, Raboy A, et al: High dose combination radiotherapy for the treatment of localized prostate cancer. J Urol 160: 91–96, 1998. 9. Iverson P, Rasmussen F, and Holm HH: Long term results of ultrasonically guided implantation of 125-I combined with external irradiation in localized prostatic cancer. Scand J Urol Nephrol Suppl 138: 109 –115, 1991. 10. Howard A, Wallner K, Han B, et al: Clinical course and
636
dosimetry of rectal fistulas after prostate brachytherapy. J Brachyther Int 17: 37– 42, 2001. 11. Blasko JC, Ragde H, Luse RW, et al: Should brachytherapy be considered a therapeutic option in localized prostate cancer? Urol Clin North Am 23: 633– 650, 1996. 12. Gelblum DY, Potters L, Ashley R, et al: Urinary morbidity following ultrasound-guided transperineal prostate seed implantation. Int J Radiat Oncol Biol Phys 45: 59 – 67, 1999. 13. Grimm PD, Blasko JC, Ragde H, et al: Does brachytherapy have a role in the treatment of prostate cancer? Hematol Oncol Clin North Am 10: 653– 673, 1996. 14. Hu JC, Gold KF, Pashos CL, et al: Role of surgeon volume in radical prostatectomy outcomes. J Clin Oncol 21: 401– 405, 2003. 15. Eastham JA, Kattan MW, Riedel E, et al: Variations among individual surgeons in the rate of positive surgical margins in radical prostatectomy specimens. J Urol 170: 2292– 2295, 2003.
UROLOGY 64 (4), 2004
SUMMARY OF SIMULTANEOUS IRRADIATION FOR PROSTATE CANCER FRANK A. CRITZ
A
fter our negative experience with retropubic iodine-125 implantation alone for prostate cancer, external beam radiotherapy was added after the implantation. A formal study of this treatment process was started in January 1984. Because the prostate is irradiated at the same time owing to performing an iodine-125 implant first followed by external beam radiotherapy, this method was called simultaneous irradiation (SI). A change from the retropubic to the modern ultrasound-guided transperineal implant technique as a part of SI was begun in 1992. This report summarizes the experience of this facility with SI, with the focus almost exclusively on men implanted by the transperineal technique. MATERIAL AND METHODS
Three databases were evaluated. Database 1 consisted of 5509 consecutive men with clinical Stage T1-T4NxM0 prostate cancer treated with SI using the transperineal implant technique from August 1992 to August 2002. All these men had been treated 18 or more months previously. This database was used to evaluate the treatment-related morbidity, and data were gathered through post-treatment questionnaires either mailed to men or given at each clinic follow-up visit. Database 2 was a subset of database 1 and consisted of 1658 consecutive men with Stage T1-T2NxM0 cancer and 74 consecutive men with Stage T3-T4NxM0 prostate cancer treated 5 or more years previously (August 1992 to December 1998). None of these men had received neoadjuvant androgen deprivation. This database was used to evaluate freedom from disease. The median pretreatment prostate-specific antigen (PSA) level for men with Stage T1-T2 was 7.1 ng/mL (range 0.3 to 88), and 75% had a Gleason score of 6 or less on prostate biopsy taken from unreviewed community hospital pathology reports. A median dose of 11,500 cGy calculated at the prostatic capsule was delivered by the implant using the urethralsparing technique plus implantation of the seminal vesicles. Three weeks after implantation, external beam radiotherapy was delivered to the prostate, periprostatic tissues, and seminal vesicles at a daily dose rate of 150 cGy, 5 days/wk, to a total dose of 4500 cGy. Men with a pretreatment PSA level of 10.1 ng/mL or greater, Gleason score of 7 or greater, or prostatic base involvement either by palpation or biopsy were given an additional 750-cGy boost to the base and seminal vesicles. From the Radiotherapy Clinics of Georgia, Decatur, Georgia Reprint requests: Frank A. Critz, M.D., Radiotherapy Clinics of Georgia, 2349 Lawrenceville Highway, Decatur, GA 30033 Submitted: March 25, 2004, accepted (with revisions): June 17, 2004 © 2004 ELSEVIER INC. ALL RIGHTS RESERVED
Database 3 consisted of 359 consecutive men with clinical Stage T1-T2N0M0 prostate cancer treated with SI but implanted by the obsolete retropubic implant technique between 1984 and 1995. Follow-up examinations for all men in this study were performed every 6 months. The median follow-up for database 2 was 6 years (range 3 months to 11 years). Freedom from disease was defined by a PSA cutpoint of 0.2 ng/mL, and recurrence was defined by failure to achieve a PSA level of 0.2 ng/mL or a subsequent rise to greater than this level. Disease-free survival rates were calculated by the KaplanMeier method.
RESULTS The 10-year disease-free survival rate for the contemporary series of men with clinical Stage T1-T2 disease treated since 1992 with SI using the transperineal implant technique was 83% (Fig. 1). Of the 1658 men, 236 developed recurrence at a median of 25 months (range 3 months to 8 years) after implantation. The 10-year and 15-year disease-free survival rate was 55% and 51%, respectively, for the 359 men from database 3, who had been treated with SI but implanted using the obsolete retropubic implant technique. The 10year and 15-year disease-free survival rate was 76% and 71%, respectively, for the combined series of men implanted using either the transperineal or retropubic implant technique (Fig. 1). The median time to recurrence was 30 months (range 3 months to 13.5 years) for the total group. The 5-year disease-free survival rate was 41% for men with Stage T3-T4 disease treated since 1992 with the transperineal implant method. The frequency of invasive procedures used for the management of treatment-related morbidity was documented for all 5509 men treated with SI using the transperineal approach (Table I). Because of the impact on urinary morbidity, men were subdivided according to whether they had undergone transurethral resection of the prostate (TURP) either before or after SI. COMMENT By performing radioactive iodine-125 implantation initially, which has a 60-day half-life, followed 21 days later by external beam radiotherapy given UROLOGY 64: 633– 636, 2004 • 0090-4295/04/$30.00 doi:10.1016/j.urology.2004.06.047 633
FIGURE 1. Disease-free survival rate for contemporary series of 1658 men with clinical Stage T1-T2 treated with SI using transperineal implant technique since 1992. Second disease-free survival curve combined men with Stage T1-T2 implanted by obsolete retropubic implant technique with contemporary series documenting 15-year diseasefree survival rate after SI. Number of men at risk at 5 years of follow-up was 1255 and 1489 for transperineal and combined men, respectively, and was 17 men at 15 years of follow-up.
TABLE I. Frequency of postimplant invasive procedures for complications of simultaneous irradiation No TURP Before SI Procedure
No TURP
Patient total (n) 5106 (93) Urinary (n) Postimplant catheter 316 (6.1) Cauterization 25 (0.5) Urethral stone removal 1 (0.02) Artificial sphincter 0 Urethral dilation 57 (1.1) Urethral incision 26 (0.5) Urinary diversion 0 Rectal (n) Cauterization — Colostomy —
TURP After SI 57 (1) — 0 7 (12.2) 2 (3.5) 13 (22.8) 9 (15.8) 2 (3.5) — —
TURP Before SI 346 (6) 10 (2.9) 15 (4.3) 10 (2.9) 4 (1.2) 17 (4.9) 8 (2.3) 0 — —
All 5509 (100) 326 (5.9) 40 (0.7) 18 (0.3) 6 (0.1) 87 (1.6) 43 (0.8) 2 (0.04) 62 (1.1) 7 (0.13)
KEY: TURP ⫽ transurethral resection of prostate; SI ⫽ simultaneous irradiation. Numbers in parentheses are percentages.
within 6 to 7 weeks, the radiation dose was intensified for benign and intraprostatic malignant epithelium. The external beam component also irradiated localized extracapsular disease. The theory of SI was supported by the 10-year disease-free survival rate of 83% for men with clinical Stage T1-T2 implanted using the transperineal technique in the PSA era (Fig. 1). These results are comparable to those after radical prostatectomy, the reference standard for the treatment of prostate cancer.1 Additionally, the 15-year disease-free survival rate of 71% calculated for the combined men implanted since 1984 was compara634
ble to the 66% 15-year disease-free survival rate of men treated with radical prostatectomy at Johns Hopkins University since 1982.2 However, a comparison of the outcome of radiotherapy with radical prostatectomy may be misleading, unless two issues are addressed, the definition of freedom from disease and the minimal length of follow-up. Freedom from disease in this study was defined by a PSA cutpoint of 0.2 ng/mL, the same definition used for surgery at Johns Hopkins.1,2 Additionally, all men analyzed for freedom from disease in this report had been treated 5 or more UROLOGY 64 (4), 2004
years previously. Investigators have documented that the outcome of men treated with radiotherapy is significantly lower for men with long, compared with short, follow-up.3,4 The length of follow-up may be related to the inherent difference in the time to achieve a PSA level of 0.2 ng/mL after radiotherapy compared with after radical prostatectomy. For those men who achieve a PSA nadir of 0.2 ng/mL, no more than 1 month of follow-up is required after radical prostatectomy. In contrast, 5 years of follow-up is required for the 99th percentile of men to reach a PSA nadir of 0.2 ng/mL after SI.5 A slowly falling PSA level after radiotherapy, especially if men have a PSA “bounce,” could mask an early recurrence that otherwise would be detectable with longer follow-up. Using the format described by Sarosdy,6 the treatment-related morbidity caused by SI for men implanted using the transperineal implant technique was analyzed according to the frequency of invasive procedures for the management of complications (Table I). Postimplant catheterization for urinary retention was the most common procedure after SI. Of the 5.9% of men who were catheterized after implantation, 79% were catheterized within 1 day of the implant, and the median duration of catheter use was 7 days. The median prostate volume at implantation was 35 cm3 (range 13 to 160). The catheterization rate was 4.6% for the 5119 men with a prostate size of 60 cm3 or less. Procedures for urinary morbidity are rare, overall, and are usually related to men who have undergone TURP, especially post-treatment TURP. Overall, 67 men (1.2% of the total 5509) had undergone TURP after SI, including 10 men who had undergone preimplant TURP. For example, the incidence of stone removal from the urethra was 2.9% for men who had undergone preimplant TURP and 12.3% for men who had undergone postimplant TURP, but only 0.02% for men who had never undergone TURP. Urethral dilation or incision, usually for urethral strictures, was much more common in men who had undergone either preimplant or postimplant TURP. Procedures for rectal complications were rare. Of the 7 men who had undergone colostomy for rectoprostatic fistula, 5 had undergone rectal procedures after SI but before the development of a fistula, including 3 who had undergone rectal biopsy, which has been associated with this complication,7 1 who had required cauterization, and 1 who had undergone internal hemorrhoidectomy. Prostate iodine-125 implantation followed by external beam radiotherapy has been associated with a high rate of severe complications. The rate of colostomies for rectal fistulas has ranged from 2.8% to 6%.8,9 Sarosdy6 reported on 158 men treated with palladium implants alone or comUROLOGY 64 (4), 2004
bined with external beam radiotherapy and noted that overall 20% had required a catheter after implantation, 9% had undergone postimplant TURP, and 2.6% had undergone colostomy. Complications were substantially greater for men who had undergone combined radiotherapy. Other investigators who have treated large series of men have reported urinary retention rates of 4% to 7%, postimplant TURP rates of up to 4.7%, and urinary or rectal diversion rates of 0.33% to 1.5% after seeds alone or preceded by external beam radiotherapy.10 –13 The relatively low rate of complications in this study may have been a result of several factors, including implantation of gold seeds along with the iodine seeds as a marker for postimplant radiotherapy, daily x-rays before external beam radiotherapy for verification of patient setup, a change in beam technique on the basis of patient symptoms while undergoing external beam radiotherapy, and slower than usual fractionation of the external beam because the men were receiving simultaneous treatment from the seeds. An additional factor may have been the extensive experience with SI at this facility, similar to the finding that a high surgical volume is inversely related to in-hospital complications14 and positive surgical margins.15 CONCLUSIONS In experienced hands, integration of prostate iodine-125 implantation with subsequent external beam radiotherapy produces excellent outcomes for the treatment of prostate cancer. The diseasefree survival rates after SI calculated with an undetectable PSA in men with long follow-up were comparable to those after radical prostatectomy. Treatment-related morbidity, based on an evaluation of procedures for complications, was substantially less than that reported by other investigators using combination radiotherapy and appeared similar to that after monotherapy with seed implantation. REFERENCES 1. Han M, Partin AW, Piantadosi S, et al: Era specific biochemical recurrence-free survival following radical prostatectomy for clinically localized prostate cancer. J Urol 166: 416 – 419, 2001. 2. Han M, Partin AW, Pound CR, et al: Long-term biochemical disease-free and cancer-specific survival following anatomic radical retropubic prostatectomy. Urol Clin North Am 28: 555–565, 2001. 3. Vicini FA, Kestin LL, and Martinez AA: The importance of adequate followup in defining treatment success after external beam irradiation for prostate cancer. Int J Radiat Oncol Biol Phys 45: 553–561, 1999. 4. Connell PP, Ignacia L, McBride RB, et al: Caution in interpreting biochemical control rates after treatment for pros635
tate cancer: length of followup influences results. Urology 54: 875– 879, 1999. 5. Critz FA: Time to achieve a prostate specific antigen nadir of 0.2 ng/ml after simultaneous irradiation for prostate cancer. J Urol 168: 2434 –2438, 2002. 6. Sarosdy MF: Urinary and rectal complications of contemporary prostate brachytherapy (PB) for prostate cancer (PC)(abstract). J Urol 169: 491– 492, 2003. 7. Theodorescu D, Gillenwater JY, and Koutrouvelis PG: Prostatourethral-rectal fistula after prostate brachytherapy. Cancer 89: 2085–2091, 2000. 8. Zeitlin SI, Sherman J, Raboy A, et al: High dose combination radiotherapy for the treatment of localized prostate cancer. J Urol 160: 91–96, 1998. 9. Iverson P, Rasmussen F, and Holm HH: Long term results of ultrasonically guided implantation of 125-I combined with external irradiation in localized prostatic cancer. Scand J Urol Nephrol Suppl 138: 109 –115, 1991. 10. Howard A, Wallner K, Han B, et al: Clinical course and
636
dosimetry of rectal fistulas after prostate brachytherapy. J Brachyther Int 17: 37– 42, 2001. 11. Blasko JC, Ragde H, Luse RW, et al: Should brachytherapy be considered a therapeutic option in localized prostate cancer? Urol Clin North Am 23: 633– 650, 1996. 12. Gelblum DY, Potters L, Ashley R, et al: Urinary morbidity following ultrasound-guided transperineal prostate seed implantation. Int J Radiat Oncol Biol Phys 45: 59 – 67, 1999. 13. Grimm PD, Blasko JC, Ragde H, et al: Does brachytherapy have a role in the treatment of prostate cancer? Hematol Oncol Clin North Am 10: 653– 673, 1996. 14. Hu JC, Gold KF, Pashos CL, et al: Role of surgeon volume in radical prostatectomy outcomes. J Clin Oncol 21: 401– 405, 2003. 15. Eastham JA, Kattan MW, Riedel E, et al: Variations among individual surgeons in the rate of positive surgical margins in radical prostatectomy specimens. J Urol 170: 2292– 2295, 2003.
UROLOGY 64 (4), 2004