Seed Cure Rate Studies

Studies below include the Seattle group's 13 year data for seeds alone (cure 76-80% at 13 years) with more Stock data related to PSA and Gleason, and papers by Merrick showing good results with Gleason 7 given external plus seeds (90%/5y) and good results in young men (< 62y with 98.7%/5y) and a lack of negative impact due to perineural invasion

Brachytherapy for clinically localized prostate cancer: thirteen-year disease-free survival of 769 consecutive prostate cancer patients treated with permanent implants alone.

Ragde H, Grado GL, Nadir BS. Arch Esp Urol 2001 Sep;54(7):739-47

Grado-Ragde Clinics, 1330 Meridian Ave N., Ste 300, Seattle, WA 98177, USA.

OBJECTIVE: To report 13-year biochemical disease-free survival results on 769 consecutive prostate cancer patients treated with brachytherapy alone. MATERIAL AND METHODS: Seven hundred sixty-nine patients with stage T1-T3, low to high Gleason grade prostate cancer underwent transperineal prostate implants with Iodine-125 (I-125) or Palladium-103 (Pd-103) as the sole treatment between January 1, 1987 and January 1, 1997. Median age was 69 years (range 43-92) and median follow-up was 71 months (range 18-156). The patients were divided into two risk groups (low and high risk for extra-prostatic disease) based mainly on clinical stage and Gleason score. Group 1 consisted of 542 patients, who were considered at low risk and were treated with I-125. Group 2 comprised 227 patients, who were considered higher risk and were treated with Pd-103. No patient underwent pathological staging and none received androgen ablative therapy. Treatment failure was based on our modification of the American Society for Therapeutic Radiology and Oncology's (ASTRO) recommended failure criteria, defined as 3 consecutive serum Prostate Specific Antigen (PSA) rises (1). A critical component in our modification is that the value of the third PSA rise be above 0.5 ng/mL. RESULTS: One hundred thirty-seven patients were lost to follow-up. Thirteen patients expired of non-cancer causes within 18 months of the implant. This left 619 patients for evaluation, 441 in Group 1 and 178 in Group 2. The biochemical disease-free survival rates of the 619 patients at 3, 5, 10, and 13 years were 85%, 80%, 77%, and 77%, respectively (Fig. 1). The biochemical disease-free survival rates of the 441 "lower risk" I-125 treated patients at 3, 5, 10, and 13 years were 84%, 79%, 76%, and 76%, respectively. The biochemical disease-free survival rates of the 178 "higher risk" Pd-103 treated patients at 3, 5, 10, and 13 years were 87%, 82%, 80%, and 80%, respectively (Fig. 3). CONCLUSION: The excellent long-term results presented here, as well as the many advantages of prostate brachytherapy over other common treatments, demonstrate that brachytherapy is an effective treatment for clinical organ-confined prostate cancer in the long term.

The effect of prognostic factors on therapeutic outcome following transperineal prostate brachytherapy.

Stock RG, Stone NN. Semin Surg Oncol 1997 Nov-Dec;13(6):454-60

Department of Radiation Oncology, Mount Sinai Medical Center, New York, New York 10029, USA.

The objectives of this study were to examine the effect of both disease and treatment related prognostic factors on biochemical control and post-treatment biopsy. Two-hundred fifty-eight patients underwent interactive ultrasound guided transperineal prostate implantation for T1-T2 prostate cancer using Iodine-125 (139 patients) and Palladium-103 (119 patients) and were followed from 6-67 months (median, 19). Hormonal therapy with 3 months of leuprolide and flutamide prior to implantation and two months given after the implant was used in 96 patients. Pre-treatment prostate-specific antigen (PSA) had the most significant effect on biochemical failure. Freedom from biochemical failure (FFBF) rates at 4 years were 75% for patients with PSA 1.3-10 ng/ml (144), 74% for patients with PSA 10.1-20 ng/ml (73), and 34% for patients with PSA > 20 ng/ml (41) (P = 0.0004). Gleason score also had a significant effect on FFBF rates. Four-year rates were 81%, 65% and 47% for patients with scores of 2-4 (68), 5-6 (130), and > or = 7 respectively (60) (P = 0.01). These two factors were also significant in multivariate analysis (P = 0.002, 0.007, respectively). Gleason score was the only factor to significantly affect post-treatment biopsy results. Patients with scores of 2-6 had 85% (63/ 74) negative 2-year biopsies versus 62% (13/21) for patients with scores > or = 7 (P = 0.02). Low-risk patients (PSA < or = 10 ng/ml, scores < 7 and stage < T2a) had a 4-year FFBF rate of 88% as compared to 60% for high-risk patients (PSA > 10 ng/ml, score > 6 or stage > or = T2b) (P = 0.02) and had a 95% negative biopsy rate versus 76% for high-risk patients (P = 0.06). Low-risk patients demonstrate high FFBF and negative biopsy rates following implantation. Patients presenting with higher risk prognostic factors such as PSA > 20 ng/ml or Gleason scores > or = 7 may require more aggressive treatment regimens.

Biochemical outcome for hormone-naive patients with Gleason score 3+4 versus 4+3 prostate cancer undergoing permanent prostate brachytherapy.

Merrick GS, Butler WM, Galbreath RW, Lief JH, Adamovich E. Urology 2002 Jul;60(1):98-103

Schiffler Cancer Center, Wheeling Hospital, Wheeling, West Virginia, USA

Objectives. To determine the effect of the dominant pattern in Gleason score 7 histologic findings on biochemical no evidence of disease survival for hormone-naive patients undergoing permanent prostate brachytherapy.Methods. A total of 114 hormone-naive patients with Gleason score 7 histologic findings underwent transperineal ultrasound-guided permanent prostate brachytherapy for clinical T1c-T3a NxM0 adenocarcinoma of the prostate gland from April 1995 to October 1999. No patient was lost to follow-up. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. Sixty-four patients were diagnosed with Gleason score 3+4 and 50 with Gleason score 4+3 prostate cancer. Twenty-one patients were implanted with either palladium 103 or iodine 125 monotherapy, and 93 patients received supplemental external beam radiotherapy with a brachytherapy boost. The median patient age was 69 years (range 49 to 79). The median follow-up was 46.4 months (range 20 to 80). The American Society for Therapeutic Radiology and Oncology consensus definition was used to determine the biochemical disease-free survival.Results. The actuarial 5-year biochemical disease-free survival rate was 90.3%. No statistically significant difference in outcome was found when stratified by the dominant pattern in Gleason score 7 histologic features (89.4% versus 91.5% for 3+4 and 4+3, respectively, P = 0.700). The biochemical no evidence of disease survival analysis in terms of the Gleason cohorts revealed no difference in terms of the choice of isotope, use of supplemental external beam radiotherapy, or preimplant prostate-specific antigen level. The median and mean postimplant prostate-specific antigen level was less than 0.1 ng/mL and 0.12 +/- 0.20 ng/mL, respectively, without a significant difference between Gleason score 3+4 and 4+3.Conclusions. Our results indicate that the 5-year biochemical outcome with a hormone-naive prostate brachytherapy approach that uses multiple periprostatic seeds is not dependent on Gleason score 3+4 versus 4+3 histologic features.

Five-year biochemical outcome following permanent interstitial brachytherapy for clinical T1-T3 prostate cancer.

Merrick GS, Butler WM, Galbreath RW, Lief JH. Int J Radiat Oncol Biol Phys 2001 Sep 1;51(1):41-8

Schiffler Cancer Center, Wheeling Hospital, Wheeling, WV 26003-6300, USA. schifonc@wheelinghosp.com

PURPOSE: To evaluate 5-year biochemical disease-free outcome for men with clinical T1b-T3a NxM0 1977 American Joint Committee on Cancer (1997 AJCC) adenocarcinoma of the prostate gland who underwent transperineal ultrasound-guided permanent prostate brachytherapy. METHODS AND MATERIALS: Four hundred twenty-five patients underwent transperineal ultrasound-guided prostate brachytherapy using either 103Pd or 125I, for clinical T1b-T3a NxM0 (1997 AJCC) adenocarcinoma of the prostate gland, from April 1995 to October 1999. No patient underwent pathologic lymph-node staging. One hundred ninety patients were implanted with either 103Pd or 125I monotherapy; 235 patients received moderate-dose external beam radiation therapy (EBRT), followed by a prostate brachytherapy boost; 163 patients received neoadjuvant hormonal manipulation, in conjunction with either 103Pd or 125I monotherapy (77 patients) or in conjunction with moderate-dose EBRT and a prostate brachytherapy boost (86 patients). The median patient age was 68.0 years (range, 48.2-81.3 years). The median follow-up was 31 months (range, 11-69 months). Follow-up was calculated from the day of implantation. No patient was lost to follow-up. Biochemical disease-free survival was defined by the American Society of Therapeutic Radiation and Oncology (ASTRO) consensus definition. RESULTS: For the entire cohort, the 5-year actuarial biochemical no evidence of disease (bNED) survival rate was 94%. For patients with low-, intermediate-, and high-risk disease, the 5-year biochemical disease-free rates were 97.1%, 97.5%, and 84.4%, respectively. For hormone-naive patients, 95.7%, 96.4%, and 79.9% of patients with low-, intermediate-, and high-risk disease were free of biochemical failure. Clinical and treatment parameters predictive of biochemical outcome included: clinical stage, pretreatment prostate-specific antigen (PSA), Gleason score, risk group, age > 65 years, and neoadjuvant hormonal therapy. Isotope choice was not a statistically significant predictor of disease-free survival for any risk group. The median postimplant PSA was < or = 0.2 for all risk groups, regardless of hormonal status. The mean posttreatment PSA, however, was significantly lower for men implanted with 103Pd (0.14 ng/mL) than for those implanted with 125I (0.25 ng/mL), p < or = 0.001. CONCLUSION: With a median follow-up of 31 months, permanent prostate brachytherapy results in a high probability of actuarial 5-year biochemical disease-free survival (DFS) for patients with clinical T1b-T3a (1997 AJCC) adenocarcinoma of the prostate gland, with an apparent plateau on the PSA survival curve.

Five-year biochemical outcome after prostate brachytherapy for hormone-naive men < or = 62 years of age.

Merrick GS, Butler WM, Lief JH, Galbreath RW. Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1253-7

Schiffler Cancer Center, Wheeling Hospital, Wheeling, WV 26003-6300, USA. schifonc@wheelinghosp.com

PURPOSE: To evaluate 5-year biochemical disease-free outcome for hormone naive men 62 years of age or less who underwent transperineal ultrasound-guided permanent prostate brachytherapy. METHODS AND MATERIALS: 76 patients underwent transperineal ultrasound guided prostate brachytherapy using either (103)Pd or (125)I 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, and no patient underwent pathologic lymph-node staging. 47 patients were implanted with either (103)Pd or (125)I 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. RESULTS: 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. CONCLUSION: With a median follow-up of 37 months, hormone naive patients < or = 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.

Perineural invasion is not predictive of biochemical outcome following prostate brachytherapy.

Merrick GS, Butler WM, Galbreath RW, Lief JH, Adamovich E. Cancer J 2001 Sep-Oct;7(5):404-12

Schiffler Cancer Center, Wheeling, West Virginia 26003-6300, USA.

PURPOSE: The purpose of this article is to evaluate whether the presence of perineural invasion (PNI) in the biopsy specimen is predictive of 5-year biochemical disease-free outcome after prostate brachytherapy. MATERIALS AND METHODS: Four hundred twenty-five patients underwent transperineal ultrasound-guided prostate brachytherapy using either 103Pd or 125I for clinical T1b/T3a NXMO (1997 American Joint Committee on Cancer) adenocarcinoma of the prostate gland from April 1995 to October 1999. No patient was lost to follow-up, and no patient underwent pathological lymph node staging. Two hundred twenty-one patients were implanted with 103Pd, and 204 patients were implanted with 125I. Of this cohort, 190 patients were implanted without supplemental beam radiation, and 235 received moderate-dose external-beam radiation therapy followed by a prostate brachytherapy boost. One hundred sixty-three patients received hormonal manipulation in conjunction with the brachytherapy implant (86 of these patients received moderate-dose external-beam radiation therapy before brachytherapy), and 262 patients were hormone naive. Perineural invasion, defined as carcinoma tracking along or around a nerve within the perineural space, was identified in 105 patients (24.7% of the population). The median patient age was 68 years (range, 48-81 years). The mean follow-up was 37.1 +/- 15.2 months, and the median follow-up was 35.4 months (range, 6-74 months). Follow-up was calculated from the date of implantation. Biochemical disease-free survival was defined by the American Society of Therapeutic Radiation and Oncology (ASTRO) consensus definition. RESULTS: When Kaplan-Meier survival analysis was performed, the presence of PNI did not predict failure. When PNI was entered into a Cox regression analysis with evaluated clinical predictors of failure (age, clinical T stage, pretreatment prostate-specific antigen level, and Gleason score) or treatment parameters (use of neoadjuvant hormonal therapy, supplemental external-beam radiation therapy, and choice of isotope), PNI did not add to the predictive strength of these variables. The median disease-free prostate-specific antigen level was 0.1 ng/mL for the entire cohort. CONCLUSIONS: Our results indicate that actuarial 5-year biochemical outcomes with a prostate brachytherapy approach that utilizes generous periprostatic margins is not dependent on the presence of PNI. In addition, PNI should not be used as an independent prognosticator in determining the need for combined-modality therapy in patients undergoing prostate brachytherapy.