Five-year biochemical outcome after prostate brachytherapy for hormone-naive men ≤ 62 years of age

To evaluate 5-year biochemical disease-free outcome for hormone naïve men 62 years of age or less who underwent transperineal ultrasound-guided permanent prostate brachytherapy.

76 patients underwent transperineal ultrasound guided prostate brachytherapy using either ¹⁰³Pd or ¹²⁵I for clinical T1b–T2b N×M0 (1997 AJCC) adenocarcinoma of the prostate gland from April 1995 to October 1999. No patient was lost to follow-up, and no patient underwent pathologic lymph-node staging. 47 patients were implanted with either ¹⁰³Pd or ¹²⁵I monotherapy, and 29 patients received moderate-dose external-beam radiation therapy followed by a prostate brachytherapy boost. No patient received hormonal manipulation. The median patient age was 58 years (range, 48–62 years). The median follow-up was 37 months (range, 14–70 months). Follow-up was calculated from the day of implantation. Biochemical disease-free survival was defined by the American Society of Therapeutic Radiation and Oncology (ASTRO) consensus definition.

The actuarial 5-year biochemical disease-free survival rate was 98.7%. For patients with low-, intermediate-, and high-risk disease, 97.7%, 100%, and 100%, respectively, were free of biochemical failure. The median posttreatment prostate-specific antigen (PSA) for the entire group was 0.2 ng/mL. When stratified by risk group, the median posttreatment PSA was 0.2, 0.15, and 0.1 for patients with low-, intermediate-, and high-risk disease, respectively.

With a median follow-up of 37 months, hormone naïve patients ≤ 62 years of age have a high probability of 5-year biochemical disease-free survival following permanent prostate brachytherapy with an apparent plateau on the PSA curve.     

Four-year biochemical outcome after radioimmunoguided transperineal brachytherapy for patients with prostate adenocarcinoma

PURPOSE: To evaluate 4-year biochemical outcomes for patients with prostate adenocarcinoma who underwent radioimmunoguided (Prostascint) permanent prostate brachytherapy. METHODS AND MATERIALS: Eighty patients with clinical T1C-T3A NxM0 prostate cancer underwent ProstaScint-guided prostate brachytherapy using either (103)Pd or (125)I between February 1997 and December 2000. Sixty-seven patients underwent prostate brachytherapy alone, whereas 13 patients received neoadjuvant hormonal manipulation before implantation. Risk factors (RF) included PSA >10, Stage >or=T2b, and Gleason grade >or=7. Sixty patients had low-risk disease (0 RF), 17 were intermediate risk (1 RF), and 3 were high risk (2 RF). Biochemical disease-free survival (bDFS) was calculated using the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus criteria, a PSA cutoff of 1.0 ng/mL, and a PSA cutoff of 0.5 ng/mL. RESULTS: Four-year bDFS for the entire cohort was 97.4% using the ASTRO consensus criteria. Low-risk patients (60) had a 4-year bDFS of 100%; intermediate- and high-risk patients (20 patients) were 89.2%. The hormonally na?ve group (67 patients) had a 4-year bDFS of 96.9% and a median PSA nadir of 0.2 ng/mL. Median time to nadir was 19.8 months (range: 1.9-53.2 months). For the neoadjuvant hormonal therapy group (13 patients), ASTRO-defined bDFS was 100%. Overall, 85.2% of patients had a posttreatment PSA 相似文献   

Impact of supplemental external beam radiotherapy and/or androgen deprivation therapy on biochemical outcome after permanent prostate brachytherapy

PURPOSE: To evaluate the impact of supplemental external beam radiotherapy (EBRT) and/or androgen deprivation therapy (ADT) on 8-year biochemical outcome after permanent prostate brachytherapy. METHODS AND MATERIALS: Between April 1995 and January 2001, 668 consecutive patients underwent brachytherapy using either (103)Pd or (125)I for clinical Stage T1b-T3aNxM0 (2002 American Joint Committee on Cancer) adenocarcinoma of the prostate gland. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. The median follow-up was 58.6 months. Biochemical progression-free survival was defined by the American Society for Therapeutic Radiology and Oncology consensus definition. The clinical, treatment, and dosimetric parameters evaluated for biochemical progression-free survival included supplemental EBRT, ADT, patient age, clinical stage, Gleason score, preimplant prostate specific antigen (PSA), risk group, percentage of positive biopsies, isotope used, prostate volume, planning volume, percentage of target volume receiving 100%, 150%, and 200% of prescribed dose, minimal percentage of dose covering 90% of target volume, tobacco status, hypertension, and diabetes. RESULTS: For the entire group, the actuarial 8-year biochemical progression-free survival rate was 98.2%, 98.4%, and 88.2% for low-, intermediate-, and high-risk patients, respectively, with a median PSA level of <0.1 ng/mL for all risk groups and ADT and EBRT subgroups. At last follow-up, only 5 patients (0.8%) had died of metastatic prostate cancer. In multivariate analysis, Gleason score, percentage of positive biopsies, and ADT predicted for biochemical outcome in high-risk patients. In low- and intermediate-risk patients, none of the evaluated variables predicted for biochemical outcome. For the entire population, pretreatment PSA level, Gleason score, ADT, and clinical stage predicted for 8-year biochemical progression-free survival, with the percentage of positive biopsies approaching statistical significance. CONCLUSION: Prostate brachytherapy results in a high probability of 8-year biochemical progression-free survival for low-, intermediate-, and high-risk patients. Although the role of supplemental EBRT could not be adequately evaluated in high-risk patients, it did not improve biochemical outcome in low- and intermediate-risk patients. However, ADT resulted in a statistically significant improvement in progression-free survival for high-risk patients.     

Permanent interstitial brachytherapy for clinically organ-confined high-grade prostate cancer with a pretreatment PSA < 20 ng/mL

The objective of this study was to determine the effect of biopsy Gleason score 8 and 9 histology on biochemical outcome following a permanent prostate brachytherapy approach that includes multiple periprostatic seeds and supplemental external beam radiation. Forty-six consecutive T1c-T2b (1997 AJCC) patients with Gleason score 8 and 9 prostate cancer who were either hormone naive (33 patients) or received cytoreductive (< or =6 months) hormonal therapy (13 patients) underwent brachytherapy from June 1995 to November 2000. The median patient age was 69.7 years, with a median pretreatment prostate-specific antigen (PSA) of 7.7 ng/mL. The median follow-up was 58 months (range 27-93 months). Forty-five of the patients were implanted with Pd-103 and 44 received supplemental external beam radiation therapy (45 Gy). Biochemical success was defined by either a PSA < or = 0.4 ng/mL after a nadir or by the ASTRO consensus definition. The actuarial 7-year biochemical disease-free survival was 84.8% using either a PSA < or = 0.4 ng/mL or the ASTRO consensus definition. The median postimplant PSA was less than 0.1 ng/mL for both the hormone naive and hormonally manipulated patients. The utilization of hormonal therapy for 6 months or less duration resulted in a statistically nonsignificant improvement in biochemical outcome (92.3% versus 81.8%, P = 0.393). When stratified by pretreatment PSA, 87.9% of patients with a pretreatment PSA < or = 10 ng/mL and 76.9% with a pretreatment PSA > 10 ng/mL (P = 0.377) remained biochemically free of disease. In multivariate analysis, none of the clinical, treatment, or dosimetric parameters predicted for outcome. Following a permanent prostate brachytherapy approach that used multiple periprostatic seeds, the majority of patients with clinically organ-confined Gleason score 8 and 9 prostate cancer remain biochemically free of disease with identical outcomes for both biochemical definitions of success.     

Relationship between percent positive biopsies and biochemical outcome after permanent interstitial brachytherapy for clinically organ-confined carcinoma of the prostate gland

PURPOSE: Recently, the percentage of positive prostate biopsies has been reported to be statistically significant in predicting the biochemical outcome after either radical prostatectomy or 3-dimensional conformal external beam radiotherapy. In this study, we evaluated the impact of the percentage of positive prostate biopsies in predicting the 5-year biochemical outcome for patients with clinically organ-confined prostate cancer undergoing permanent interstitial brachytherapy. METHODS AND MATERIALS: Two hundred sixty-two hormone naive patients underwent transperineal ultrasound-guided permanent prostate brachytherapy with generous periprostatic margins, using either 103Pd or 125I for clinical T1b/T2b NXM0 (1997 AJCC) adenocarcinoma of the prostate gland from April 1995 to October 1999. No patient was lost to follow-up. The actual percentage of positive biopsies (number of positive biopsies/total number of biopsies) was determinable for 255 of the 262 patients. Of the evaluated cases, 133 patients were implanted with 103Pd and 122 patients with 125I. The median patient age was 68 years (range 48-81). The median follow-up was 38.6 months (range 6-73). Follow-up was calculated from the day of implantation. Patients were stratified by the percentage of positive biopsies into the following groups: <34%, 34-50%, and >50%. Additional clinical parameters evaluated included patient age, clinical T-stage, Gleason score, pretreatment prostate specific antigen (PSA), risk group, and prostate volume. Low-risk patients were staged as clinical T1c/T2a, Gleason score < or =6, and pretreatment PSA < or =10 ng/mL, intermediate-risk patients presented with one unfavorable prognostic parameter, and high-risk patients presented with two or more unfavorable prognostic parameters (clinical stage T2b, PSA >10 ng/mL, Gleason score > or =7). Treatment parameters included the use of supplemental external beam radiation and choice of isotope. Biochemical disease-free survival was defined by the American Society of Therapeutic Radiation and Oncology consensus definition. RESULTS: For the 255 evaluated patients, the 5-year actuarial biochemical no evidence of disease survival rate was 92.5%. For patients with low, intermediate, and high-risk disease, 95.8%, 98.1%, and 79.4% of patients were free of biochemical failure, respectively. When each risk group was stratified into the percent positive biopsy categories of <34%, 34-50%, and >50%, no statistical difference was found in biochemical outcome for the biopsy subgroups. In multivariate analysis, none of the clinical or treatment parameters predicted for failure in the low-risk group; only Gleason score was predictive for intermediate-risk patients and only PSA for high-risk patients. In the overall population, PSA and Gleason score were both found to be predictors of biochemical failure, but not risk group, clinical stage, or percentage of positive biopsies. There was no significant dependence between the percent positive biopsy group and the Kaplan-Meier biochemical survival rates for any of the various subgroups of clinical and treatment parameters, except for clinical stage T1c-T2a (p = 0.006). The median postimplant PSA was 0.2 ng/mL for patients with either low-risk disease or <34% positive biopsies and 0.1 ng/mL for all other risk groups or percent positive biopsy subgroups. CONCLUSION: Although a significant trend was found for biochemical failure with increasing percent positive biopsies in the overall population, our results suggest that the percentage of positive biopsies is not statistically significant in predicting the 5-year biochemical disease-free outcome for patients with low, intermediate, and high-risk disease undergoing permanent prostate brachytherapy. Only the Gleason score in intermediate-risk patients and the pretreatment PSA level in high-risk patients was predictive of biochemical failure. We believe this relative lack of significance for the percentage of positive biopsies is a result of dose escalation far exceeding other radiotherapy modalities and the ability to aggressively treat the periprostatic region compared with radical prostatectomy by way of the accurate placement of periprostatic seeds.     

Prostate-specific antigen spikes after permanent prostate brachytherapy

PURPOSE: To evaluate whether any clinical, treatment, or dosimetric parameters correlated with the development of a prostate-specific antigen (PSA) spike after permanent prostate brachytherapy. METHODS AND MATERIALS: The evaluated population consisted of 218 hormone-naive patients free of biochemical or clinical failure who underwent permanent prostate brachytherapy with or without supplemental external beam radiotherapy for clinical Stage T1b-T3a adenocarcinoma of the prostate gland (1997 AJCC) between August 1995 and November 1999. No patient underwent pre- or postimplant hormonal manipulation, pretreatment seminal vesicle biopsy, or pathologic lymph node staging. In addition, none of the 218 patients possessed equivocal biochemical results (one or two consecutive PSA rises or a declining PSA >1.0 ng/mL). The median patient follow-up was 46.2 months. A PSA spike was defined as a rise of >or=0.2 ng/mL, followed by a durable decline. The clinical parameters evaluated included patient age, clinical T stage, Gleason score, pretreatment PSA level, prostate volume, brachytherapy planning volume, and patient follow-up in months. The evaluated treatment parameters included isotope and use of supplemental external beam radiotherapy. The dosimetric parameters evaluated included the minimal dose received by 90% of the prostate gland (D(90)), the percentage of the prostate volume receiving 100% (V(100)), 150%, and 200% (V(200)) of the prescribed minimal peripheral dose, and the mean, median, maximal, and minimal urethral doses. Biochemical disease-free survival was defined by the American Society for Therapeutic Radiology and Oncology consensus definition with the additional constraint that the most recent PSA level was 0.2 to 0.5 to 1.0 ng/mL (20%, 50%, and 80%, respectively, p <0.001). In Cox multivariate regression analysis, patient age, clinical stage, first postimplant PSA level, and V(150) were predictive for the development of a PSA spike. A postimplant dosimetric threshold of either <115% of the minimal peripheral dose for D(90) or <55% of the prostate volume for V(150) was strongly predictive of a spike. When the variables only determinable after the occurrence of the PSA spike were included in the multivariate analysis, V(150), preimplant PSA level, and nadir PSA were the significant predictors. CONCLUSION: Of the patients, 23.9% developed a PSA spike with a median time to development of 16.3 months and a median prespike and median postspike PSA of 0.50 ng/mL and 0.90 ng/mL, respectively. In multivariate analysis, patient age, clinical stage, first postimplant PSA level, and V(150) were predictive for the development of a PSA spike. At approximately 66 months after implantation, the PSA curves converged for spike and nonspike patients, with a median PSA level <0.1 ng/mL.     

Isotope selection for patients undergoing prostate brachytherapy.

PURPOSE: Ultrasound-guided transperineal interstitial permanent prostate brachytherapy (TIPPB) is generally performed with either 103Pd or 125I. The use of 125I for low Gleason score tumors and 103Pd for higher Gleason scores has been suggested based on isotope dose rate and cell doubling time observed in in vitro studies. While many centers follow these isotope selection criteria, other centers have elected to use only a single isotope, regardless of Gleason score. No clinical data have been published comparing these isotopes. This study was undertaken to compare outcomes between 125I and 103Pd in a matched pair analysis for patients undergoing prostate brachytherapy. METHODS AND MATERIALS: Six hundred forty-eight consecutively treated patients with clinically confined prostate cancer underwent TIPPB between June 1992 and February 1997. Five hundred thirty-two patients underwent TIPPB alone, whereas 116 received pelvic external beam irradiation and TIPPB. Ninety-three patients received androgen deprivation therapy prior to TIPPB. The prescribed doses for TIPPB were 160 Gy for 125I (pre-TG43) and 120 Gy for 103Pd. Patients treated with combination therapy received 41.4 or 45 Gy (1.8 Gy/fraction) external beam irradiation followed by a 3- to 5-week break and then received either a 120-Gy 125I or a 90-Gy 103Pd implant. Until November 1994, all patients underwent an 125I implant after which the isotope selection was based on either Gleason score (Gleason score 2-5:125I; Gleason 5-8:103Pd) or isotope availability. A matched pair analysis was performed to assess any difference between isotopes. Two hundred twenty-two patients were matched according to Gleason score, prostate-specific antigen (PSA), and stage. PSA relapse-free survival (PSA-RFS) was calculated based on the American Society for Therapeutic Radiology and Oncology (ASTRO) Consensus Group definition of failure. Kaplan-Meier actuarial survival curves were compared to assess differences in pretreatment PSA and Gleason score. RESULTS: Univariate analysis of the 648 patients identified Gleason score, pretreatment PSA value, and stage as significant factors to predict PSA-RFS, but failed to identify isotope selection as significant. To address the significance of isotope selection further, the matched pair groupings were performed. The minimum follow-up for all 222 matched patients is 24 months with a median follow-up of 42 months (24-82). The actuarial PSA-RFS at 5 years for all 222 patients is 86.5%. One hundred eleven of the 222 matched patients received a 103Pd implant with an 87.1% 5-year PSA-RFS. The remaining 111 patients underwent a 125I implant with an 85.9% 5-year PSA-RFS (p = n.s.). Analysis of Gleason score subgroups 2-4, 5-6, and 7-9 failed to show any significant difference in PSA-RFS comparing isotopes. Pretreatment PSA subgroups of < or = 10 or > 10 ng/ml also failed to show any significant difference in PSA-RFS survival comparing isotopes. Analysis of postimplant dosimetry using dose delivered to 90% of the prostate volume (D90) did not identify any difference between the isotope groups. CONCLUSIONS: This matched pair analysis failed to demonstrate a difference for 125I and 103Pd in PSA-RFS for patients undergoing TIPPB. In addition, there were no observed advantages for either 125I or 103Pd in either the low or high Gleason score groups. This data indicates that the role of isotope selection for patients undergoing TIPPB requires further clarification.     

Modern brachytherapy for treatment of prostate cancer.

BACKGROUND: Prostate cancer is the most common cancer diagnosed in men. An increasing number of these patients are seeking minimally invasive procedures such as transperineal interstitial permanent radioactive seed prostate brachytherapy. METHODS: This paper reviews the historical perspective and the current advances in transperineal interstitial permanent radioactive seed prostate brachytherapy. The 10- to 15-year results data now published for brachytherapy alone or in combination with external-beam irradiation are also reviewed. RESULTS: Modern brachytherapy using transperineal interstitial permanent radioactive seed prostate brachytherapy offers patients an excellent quality of life with convenient outpatient treatment with long-term (10- to 15-year) biochemical relapse-free survival rates ranging from 67% to 87%, depending on risk stratification. CONCLUSIONS: Modern-day brachytherapy utilizing either radioactive iodine-125 or palladium-103 alone or in combination with supplemental external-beam treatment offers patients a successful treatment outcome with acceptable toxicity.     

Brachytherapy with transperineal (125)Iodine seeds for localized prostate cancer.

BACKGROUND AND PURPOSE: To analyze the treatment results of transperineal (125)Iodine seeds in localized prostate cancer. PATIENTS AND METHODS: Between 1985 and 1996, 102 patients with T1-T2 N0 prostate cancer were treated with transperineal (125)Iodine seed implants at the Academic Medical Centre in Amsterdam. Tumours were classified as T1c in four patients, T2a in 73 patients and T2b in 25 patients. The mean pre-treatment PSA was 17 ng/ml. The (125)Iodine seeds were implanted transperineally under transrectal ultrasound guidance. The mean prostate volume was 31 ml (range 15-48 ml). An average of 49 seeds (range 29-74) was implanted. The dose to the periphery of the prostate was 160 Gy. Until 1988, 27 patients had additional external pelvic irradiation to a dose of 40 Gy in 20 daily fractions of 2 Gy. RESULTS: The 5- and 7-year actuarial survival rates were 77 and 63%, respectively (median 102 months). Ten patients (9.5%) died from prostate cancer. The 5- and 7-year clinical progression rates were 12 and 17%, respectively. Biochemical failure rates at 5 and 7 years were 39 and 44%, respectively. Age, alkaline phosphatase, creatinine, differentiation grade, additional treatment, staging procedure, number of seeds, prostate volume, treatment period and PSA were analyzed as prognostic factors. Only pre-treatment PSA was a prognosticator of clinical and biochemical outcome but not of survival. Biochemical control at 6 years varied from 30% for pre-treatment PSA values higher than 20 ng/ml to 95% for values < or =8 ng/ml. Forty-one out of 49 patients who were sexually active before brachytherapy maintained sexual function during the follow-up. Complete urinary incontinence occurred in one patient. No rectal complications were seen in patients receiving brachytherapy alone. CONCLUSIONS: Transperineal (125)Iodine seeds brachytherapy in localized prostate cancer achieves a good clinical control and overall survival with acceptable late toxicity. Biochemical failure was strongly correlated to the pre-treatment PSA value.     

Isotope and patient age predict for PSA spikes after permanent prostate brachytherapy

PURPOSE: To evaluate prostate-specific antigen (PSA) spikes after permanent prostate brachytherapy in low-risk patients. METHODS AND MATERIALS: The study population consisted of 164 prostate cancer patients who were part of a prospective randomized trial comparing (103)Pd and (125)I for low-risk disease. Of the 164 patients, 61 (37.2%) received short-course androgen deprivation therapy. The median follow-up was 5.4 years. On average, 11.1 post-treatment PSA measurements were obtained per patient. Biochemical disease-free survival was defined as a PSA level of < or =0.40 ng/mL after nadir. A PSA spike was defined as an increase of > or =0.2 ng/mL, followed by a durable decline to prespike levels. Multiple parameters were evaluated as predictors for a PSA spike. RESULTS: Of the 164 patients, 44 (26.9%) developed a PSA spike. Of the 46 hormone-naive (125)I patients and 57 hormone-naive (103)Pd patients, 21 (45.7%) and 8 (14.0%) developed a PSA spike. In the hormone-naive patients, the mean time between implantation and the spike was 22.6 months and 18.7 months for (125)I and (103)Pd, respectively. In patients receiving neoadjuvant androgen deprivation therapy, the incidence of spikes was comparable between isotopes ((125)I 28.1% and (103)Pd 20.7%). The incidence of spikes was substantially different in patients <65 years vs. > or =65 years old (38.5% vs. 16.3%). On multivariate Cox regression analysis, patient age (p < 0.001) and isotope (p = 0.002) were significant predictors for spike. CONCLUSION: In low-risk prostate cancer, PSA spikes are most common in patients implanted with (125)I and/or <65 years of age. Differences in isotope-related spikes are most pronounced in hormone-naive patients.     

Multi-institutional analysis of long-term outcome for stages T1-T2 prostate cancer treated with permanent seed implantation

PURPOSE: To assess long-term prostate-specific antigen (PSA) outcome after permanent prostate brachytherapy (BT) and identify predictors of improved disease-free survival. METHODS AND MATERIALS: Eleven institutions combined data on 2,693 patients treated with permanent interstitial BT monotherapy for T1-T2 prostate cancer. Of these patients, 1,831 (68%) were treated with I-125 (median dose, 144 Gy) and 862 (32%) were treated with Pd-103 (median dose, 130 Gy). Criteria for inclusion were: available pre-BT PSA, BT > or =5 years before data submission, BT between 1988-1998, and no androgen deprivation before failure. The median follow-up was 63 months. RESULTS: Among patients where the I-125 dose to 90% of the prostate (D90) was > or =130 Gy, the 8-year PSA relapse-free survival (PRFS) was 93% compared with 76% for those with lower D90 dose levels (p < 0.001). A multivariable analysis identified tumor stage (p = 0.002), Gleason score (p < 0.001), pretreatment PSA level (p < 0.001), treatment year (p = 0.001), and the isotope used (p = 0.004) as pretreatment and treatment variables associated with PRFS. When restricted to patients with available postimplantation dosimetric information, D90 emerged as a significant predictor of biochemical outcome (p = 0.01), and isotope was not significant. The 8-year PRFS was 92%, 86%, 79%, and 67%, respectively, for patients with PSA nadir values of 0-0.49, 0.5-0.99, 1.0-1.99, and >2.0 ng/mL (p < 0.001). Among patients free of biochemical relapse at 8 years, the median nadir level was 0.1 ng/mL, and 90% of these patients achieved a nadir PSA level <0.6 ng/mL. CONCLUSIONS: Outcome after permanent BT for prostatic cancer relates to tumor stage, Gleason score, pretreatment PSA, BT year, and post-BT dosimetric quality. PSA nadir < or =0.5 ng/mL was particularly associated with durable long-term PSA disease-free survival. The only controllable factor to impact on long-term outcome was the D90 which is a reflection of implant quality.     

Risk profiles to predict PSA relapse-free survival for patients undergoing permanent prostate brachytherapy.

PURPOSE: Combined risk profiles are helpful in assessing the likelihood of prostate-specific antigen relapse-free survival (PSA-RFS) for patients with localized prostate cancer. This retrospective analysis reports the 5-year biochemical outcome of a large cohort of patients according to prognostic factors and risk profiles for patients undergoing ultrasound-guided transperineal interstitial permanent prostate brachytherapy (TIPPB). PATIENTS AND METHODS: Seven hundred seventeen consecutive patients with clinically localized prostate cancer treated between June 1992 and November 1997 underwent TIPPB. Palladium-103 (103Pd) (n = 539) or iodine-125 (125I) (n = 178) sources were utilized to a prescribed dose of 120 Gy and 144 Gy, respectively. One hundred eleven patients received combined external-beam irradiation (41.4 or 45 Gy) and TIPPB (103Pd, 90 Gy, and 125I, 108 Gy). One hundred twelve patients received androgen ablation therapy in advance of TIPPB. Patients were grouped into risk profiles based on pretreatment factors that consisted of PSA < or = 10 and Gleason score < or = 6. Patients meeting both criteria were classified as favorable (n = 334). Those not fulfilling one criteria were classified as intermediate risk (n = 261), and those not fulfilling two criteria were classified as unfavorable risk (n = 261). PSA-RFS was calculated based on the American Society of Therapeutic Radiology and Oncology consensus conference definition of PSA failure. The median follow-up was 41 months (range, 14-82 months). RESULTS: The actuarial PSA-RFS survival at 5 years was 82%. Multivariate Cox regression analysis identified PSA and Gleason score as highly significant factors predicting for biochemical outcome. Hazard risk ratios using a nadir definition of the PSA as < or = 1.0 ng/mL and < or = 0.5 ng/mL were each significant predictors of outcome with the 0.5 ng/mL nadir level only slightly better (risk ratio for nadir < or = 1.0 = 2.78; risk ratio for nadir < or = 0.5 = 3.57). Favorable-risk patients had a 5-year actuarial PSA-RFS of 93%, whereas intermediate-risk and unfavorable-risk groups had 5-year PSA-RFSs of 77% and 62%, respectively. Four hundred ninety-three patients underwent brachytherapy without external-beam irradiation or androgen ablation. From this group, the 5-year PSA-RFSs for the favorable-risk, intermediate-risk, and unfavorable-risk patients were 92%, 74%, and 55%, respectively. DISCUSSION: This retrospective study examining TIPPB demonstrated excellent 5-year actuarial PSA-RFS rates. The assignment of risk profiles based on the results of multivariate analysis of prognostic factors identifies the expected PSA-RFS for patients undergoing TIPPB.     

辅助内分泌治疗配合放射性粒子组织间植入治疗局限性前列腺癌

 目的 探讨辅助内分泌治疗配合放射性粒子组织间植入治疗局限性前列腺癌的安全性和有效性。方法 22例T1 ~ T2c前列腺癌患者在采用直肠超声引导经会阴穿刺放射性125I粒子组织间植入治疗前后，给予辅助内分泌治疗4 ~ 7个月。术前2 ~ 4个月，术后1 ~ 4个月。结果 22例手术均顺利完成，手术时间60 ~ 120 min，植入125I粒子40 ~ 75枚，术后随访12 ~ 48个月，前列腺特异性抗原（PSA）＜1 ng／ml 15例，1 ng／ml≤PSA＜2 ng／ml 2例，PSA≥2 ng／ml 5例。结论 辅助内分泌治疗配合放射性粒子组织间植入治疗局限性前列腺癌安全有效     

Biochemical outcomes after prostate brachytherapy with 5-year minimal follow-up: importance of patient selection and implant quality

PURPOSE: A prostate brachytherapy program was initiated in 1990, when comparatively little was known of the relative importance of disease- and treatment-related factors on outcome. Patients treated during the first 6 years of the program were analyzed to determine the value of patient selection and implant quality on biochemical control. METHODS AND MATERIALS: We treated 243 patients with clinically localized prostate cancer with radioactive seed implantation and underwent 1-month CT-based dosimetric analysis. Follow-up ranged from 61 to 135 months (median 75). The Gleason score was < or =6 in 78% (n = 189), 7 in 14% (n = 35), and 8-10 in 8% (n = 19). The initial prostate-specific antigen (PSA) level was < or =10 ng/mL in 61% (n = 149), 10.1-20 ng/mL in 26% (n = 63), and >20 ng/mL in 13% (n = 31). The disease stage was T2a or less in 49% (n = 120), and Stage T2b-T2c in 51% (n = 123). A real-time ultrasound-guided technique was used with (125)I (n = 138) and (103)Pd (n = 105) isotopes. No patient underwent external beam radiotherapy as part of their primary treatment. Of the 243 patients, 60% also received hormonal ablation for at least 3 months before and 2-3 months after seed implantation. All patients included underwent a 1-month CT-based dosimetric analysis. The implant dose was defined as the dose delivered to 90% of the prostate volume on postimplant dosimetry (D(90)). On the basis of prior dose-response analyses, patients were retrospectively grouped into optimal D(90) ((125)I > or =140 Gy Task Group 43 or (103)Pd >/=100 Gy) and suboptimal D(90) ( (125)I <140 Gy or (103)Pd <100 Gy) dose groups. Biochemical failure was defined using the American Society for Therapeutic Radiology Oncology definition. RESULTS: Disease-related factors, including initial PSA level, Gleason score, and stage, were significant predictors of biochemical failure. The actuarial 8-year freedom from biochemical failure (bFFF) rate was 80% for those with a PSA level < or =10 ng/mL, 86% for PSA 10.1-20 ng/mL, and 45% for PSA >20 ng/mL (p = 0.0019). Patients with a Gleason score of < or =6 had an 8-year bFFF rate of 81% vs. 67% for those with Gleason score 7 and 53% for those with Gleason score 8-10 (p = 0.0003). Patients with Stage T2a or less had an 8-year bFFF rate of 85% compared with 69% for those with Stage T2b-T2c (p = 0.013). The 8-year bFFF rate was 88% for low-risk patients (Stage T2a or less, Gleason score < or =6, and initial PSA level < or =10 ng/mL; n = 75), 81% for moderate-risk patients (Stage T2b or Gleason score 7 or initial PSA level >10.1-20 ng/mL; n = 70), and 65% for high-risk patients (two or more moderate-risk features or Gleason score > or =8 or initial PSA level >20 ng/mL; n = 98; p = 0.0009). Patients with optimal dose implants (n = 145) had an 8-year bFFF rate of 82% compared with 68% for those with suboptimal dose implants (n = 98; p = 0.007). Hormonal therapy did not significantly affect biochemical failure (p = 0.27). In multivariate analysis, the statistically significant variables included initial PSA level (p <0.0001), Gleason score (p = 0.024), and dose group (p = 0.046). Because our current practice limits implantation alone to low-risk patients, an analysis of this subgroup was undertaken to validate the importance of dose. In the optimal dose group, low-risk patients had an 8-year bFFF rate of 94% vs. 75% for the low-risk patients in the suboptimal dose group (p = 0.02). CONCLUSION: With minimal follow-up of 5 years, these data continue to support the use of implantation alone in low-risk prostate cancer patients and demonstrate the importance of implant quality (dose) in achieving optimal outcomes. Low-risk patients who receive an optimal dose implant have a 94% bFFF rate at 8 years.     

Ten-year biochemical relapse-free survival after external beam radiation and brachytherapy for localized prostate cancer: the Seattle experience

PURPOSE: The role of external beam radiation therapy in addition to brachytherapy continues to be scrutinized for long term control of PSA levels after prostate cancer diagnosis. METHODS AND MATERIALS: We report 10-year biochemical relapse-free survival (BRFS) on 232 patients presenting with localized prostate cancer and consecutively treated with iodine(125) (I(125)) or palladium(103) (Pd(103)) brachytherapy and neoadjuvant external beam radiation therapy. Multivariate regression analysis was used to create a pretreatment clinical prognostic risk model using a modified ASTRO consensus definition (two consecutive rises in serum PSA) as the outcome. Gleason scoring was performed by pathologists at a small community hospital. Derived risk categories are the following: low = PSA 10 ng/mL or Gleason Score >or=7 or stage >or=T2c (1 intermediate risk factor); and high = 2 or more intermediate risk factors. Time to PSA failure (local, distant, or biochemical) was calculated and compared using Kaplan-Meier plots. RESULTS: Ten-year BRFS for the entire treatment group was 70%. Biochemical control rates by risk cohort analysis (95% confidence interval): low risk, 85% (83.3-90.7%); intermediate risk, 77% (73.0-84.5%); and high risk, 45% (45.4-57.2%). Using a risk grouping proposed by the Mt. Sinai group, the BRFS was: low risk, 84%; intermediate risk, 93%; and high risk, 57%. Grouping by the risk classification used by D'Amico, the BRFS was: low risk, 86%; intermediate risk, 90%; and high risk, 48%. CONCLUSIONS: I(125) or Pd(103) brachytherapy, as a boost combined with EBRT, continues to result in high rates of biochemical control at 10 years. Different risk group classification schemes lead to different BRFS results.     

Actuarial disease-free survival after prostate cancer brachytherapy using interactive techniques with biplane ultrasound and fluoroscopic guidance

Purpose: To evaluate the effectiveness and safety of interactive transperineal brachytherapy under biplane ultrasound and fluoroscopic guidance in patients with localized prostate cancer.Methods and Materials: Brachytherapy using ¹²⁵I or ¹⁰³Pd radioactive seeds either alone or in combination with adjunctive external beam radiotherapy (XRT) was administered to 490 patients at a single institution. Post-treatment follow-up included clinical assessment of disease status, assays of serum prostate-specific antigen (PSA) levels and documentation of treatment-related symptoms and complications.Results: Actuarial disease-free survival at 5 yr was 79% (95% CI, 71–85%), and the 5-yr actuarial rate of local control was 98% (95% CI, 94–99%). Post-treatment PSA nadir and pretreatment PSA level were found to be significant predictors of disease-free survival. In patients with a PSA nadir < 0.5 ng/ml, 5-yr disease-free survival was 93% (95% CI, 84–97%), compared with 25% (95% CI, 5–53%) in patients whose PSA nadir was 0.5–1.0 ng/ml and 15% (95% CI, 3–38) in patients with a PSA nadir > 1.0 ng/ml. Brachytherapy was well tolerated with few post-treatment complications.Conclusion: A broad range of patients with localized prostate cancer can benefit from transperineal brachytherapy with minimal morbidity. A post-treatment PSA nadir below 0.5 ng/ml provides a useful prognostic indicator of favorable long-term outcome.     

The effect of disease and treatment-related factors on biopsy results after prostate brachytherapy: implications for treatment optimization

BACKGROUND: Posttreatment prostate biopsy is a method of assessing local control after irradiation for prostate carcinoma. An analysis of the effect of disease- and treatment-related factors on biopsy results after prostate brachytherapy was performed to aid in patient selection and treatment optimization. METHODS: Two hundred sixty-eight patients underwent posttreatment prostate biopsy (6-8 cores) 2 years after brachytherapy alone without external beam irradiation. Follow-up ranged from 24 to 111 months (median, 43 months). Implants were performed using a real-time ultrasound guided technique with the isotopes (125)I in 186 and (103)Pd in 82 patients. Ninety-eight patients underwent hormonal therapy (HT) 3 months before and 2-3 months after implant. Implant dose was defined as the D90 (dose delivered to 90% of the gland from the dose volume histogram generated using 1-month computed tomography-based dosimetry). RESULTS: Overall, 89% of patients (238 of 268) had negative biopsies. A positive biopsy was a predictor of biochemical failure. Patients with a positive biopsy had a 5-year freedom from biochemical failure of 40% versus 76% for patients with a negative biopsy (P = 0.0003). Univariate and multivariate analysis found that risk group, HT, and implant dose significantly affected biopsy outcome. Patients with low risk features (prostate specific antigen [PSA] 10 ng/mL or Gleason score >/= 7 or classification T2b or higher) (n = 164) (P = 0.008). Hormonal therapy was associated with a negative biopsy rate of 98% versus 84% for implant alone (P = 0.003). Patients receiving a high implant dose (D90 >/= 140 grays [Gy] for (125)I or >/= 100 Gy for (103)Pd) (n = 174) had a negative biopsy rate of 95% versus 77% for those receiving a low dose (D90 < 140 Gy for (125)I or < 100 Gy for (103)Pd) (n = 87; P < 0.001). CONCLUSIONS: Biopsy results support the use of brachytherapy without external beam irradiation for patients with low risk features and highlight the importance of achieving an adequate implant dose.     

Interim report of image-guided conformal high-dose-rate brachytherapy for patients with unfavorable prostate cancer: the William Beaumont phase II dose-escalating trial

PURPOSE: We analyzed our institution's experience treating patients with unfavorable prostate cancer in a prospective Phase II dose-escalating trial of external beam radiation therapy (EBRT) integrated with conformal high-dose-rate (HDR) brachytherapy boosts. This interim report discusses treatment outcome and prognostic factors using this treatment approach. METHODS AND MATERIALS: From November 1991 through February 1998, 142 patients with unfavorable prostate cancer were prospectively treated in a dose-escalating trial with pelvic EBRT in combination with outpatient HDR brachytherapy at William Beaumont Hospital. Patients with any of the following characteristics were eligible: pretreatment prostate-specific antigen (PSA) >/= 10.0 ng/ml, Gleason score >/= 7, or clinical stage T2b or higher. All patients received pelvic EBRT to a median total dose of 46.0 Gy. Pelvic EBRT was integrated with ultrasound-guided transperineal conformal interstitial iridium-192 HDR implants. From 1991 to 1995, 58 patients underwent three conformal interstitial HDR implants during the first, second, and third weeks of pelvic EBRT. After October 1995, 84 patients received two interstitial implants during the first and third weeks of pelvic EBRT. The dose delivered via interstitial brachytherapy was escalated from 5.50 Gy to 6.50 Gy for each implant in those patients receiving three implants, and subsequently, from 8.25 Gy to 9.50 Gy per fraction in those patients receiving two implants. To improve implant quality and reduce operator dependency, an on-line, image-guided interactive dose optimization program was utilized during each HDR implant. No patient received hormonal therapy unless treatment failure was documented. The median follow-up was 2.1 years (range: 0.2-7.2 years). Biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. RESULTS: The pretreatment PSA level was >/= 10.0 ng/ml in 51% of patients. The biopsy Gleason score was >/= 7 in 58% of cases, and 75% of cases were clinical stage T2b or higher. Despite the high frequency of these poor prognostic factors, the actuarial biochemical control rate was 89% at 2 years and 63% at 5 years. On multivariate analysis, a higher pretreatment PSA level, higher Gleason score, higher PSA nadir level, and shorter time to nadir were associated with biochemical failure. In the entire population, 14 patients (10%) experienced clinical failure at a median interval of 1.7 years (range: 0.2-4.5 years) after completing RT. The 5-year actuarial clinical failure rate was 22%. The 5-year actuarial rates of local failure and distant metastasis were 16% and 14%, respectively. For all patients, the 5-year disease-free survival, overall survival, and cause-specific survival rates were 89%, 95%, and 96%, respectively. The 5-year actuarial rate of RTOG Grade 3 late complications was 9% with no patient experiencing Grade 4 or 5 acute or late toxicity. CONCLUSION: Pelvic EBRT in combination with image-guided conformal HDR brachytherapy boosts appears to be an effective treatment for patients with unfavorable prostate cancer with minimal associated morbidity. Our dose-escalating trial will continue.     

The dosimetry of prostate brachytherapy-induced urethral strictures

PURPOSE: There is a paucity of data regarding the incidence of urethral strictures after prostate brachytherapy. In this study, we evaluate multiple clinical, treatment, and dosimetric parameters to identify factors associated with the development of brachytherapy-induced urethral strictures. METHODS AND MATERIALS: 425 patients underwent transperineal ultrasound-guided prostate brachytherapy using either (103)Pd or (125)I for clinical T1b/T3a NxM0 (1997, American Joint Committee on Cancer) adenocarcinoma of the prostate gland from April 1995 to October 1999. No patient was lost to follow-up. 221 patients were implanted with (103)Pd and 204 patients with (125)I. The median patient age was 68 years (range 48-81 years). The median follow-up was 35.2 months (range 15-72 months). Follow-up was calculated from the day of implantation. Thirteen patients developed brachytherapy-induced strictures, and all strictures involved the membranous urethra. A control group of 35 patients was rigorously matched to the stricture patients in terms of treatment approach; i.e., choice of isotope, plus or minus radiation therapy, and plus or minus hormonal manipulation. Nine of the 13 stricture patients had detailed Day 0 urethral dosimetry available for review. The apex of the prostate gland and the membranous urethra were defined by CT evaluation. Urethral dosimetry was reported for the prostatic urethra, the apical slice of the prostate gland, and the membranous urethra which was defined as extending 20 mm in length. RESULTS: The 5-year actuarial risk of a urethral stricture was 5.3%, with a median time to development of 26.6 months (range 7.8-44.1 months). Of multiple clinical and treatment parameters evaluated, only the duration of hormonal manipulation (>4 months, p = 0.011) was predictive for the development of a urethral stricture. The radiation dose to the membranous urethra was significantly greater in patients with strictures than those without: 97.6% +/- 20.8% vs. 81.0% +/- 19.8% of prescribed minimum prostate dose, mPD (p = 0.031). The urethral dose 20 mm distal to the prostate apex was 57.6% +/- 23.8% vs. 31.5% +/- 13.9% of mPD for the stricture and control patients, respectively (p = 0.011). In addition, the extent of the 75% mPD and 50% mPD levels beyond the prostatic apex was also significantly greater for stricture patients, 16.6 +/- 5.3 mm vs. 11.9 +/- 4.5 mm (p = 0.010) and 19.0 +/- 3.2 mm vs. 16.0 +/- 3.4 mm (p = 0.021), respectively. Dose to the prostatic urethra was not predictive of stricture, but the magnitude and extent of high-dose regions within the prostate were predictive of stricture. Twelve of the 13 patients who developed urethral strictures were successfully managed by dilatation/transurethral incision. To date, 1 of the 12 patients has required a second dilatation. The remaining patient developed an iatrogenic induced injury and was catheter-dependent for 6 months. CONCLUSIONS: After prostate brachytherapy, the actuarial 5-year incidence of urethral strictures is 5.3% with a median time to development of 26.6 months. All strictures involved the membranous urethra and occurred within the first 44 months after brachytherapy. In most cases, membranous urethral strictures are easily managed with dilatation/incision. Factors predicting for the development of a urethral stricture included the magnitude and extent of high-dose regions within the prostate, the mean membranous urethra dose and the dose 20 mm distal to the prostatic apex, the maximum extent along the membranous urethra of certain dose levels, and the duration of hormonal manipulation.