Pretreatment Pretreatment Prostate-specific Antigen Research Articles

High Dose Rate and External Beam Radiotherapy in Locally Advanced Prostate Cancer

To report the outcomes and toxicity of high dose rate brachytherapy as a boost for localized prostate cancer. Between 1997 and 2000, the medical records of 131 patients with prostate adenocarcinoma who were treated with external beam radiation therapy and high dose rate brachytherapy, were retrospectively analyzed. Furthermore, 55% of the patients received neoadjuvant/concurrent or adjuvant androgen deprivation therapy. Patients were stratified into 2 groups. Group 1 included 65 patients with Gleason score 7, pretreatment prostate specific antigen (PSA) between 10 and 20 ng/mL, and clinical stage T2b. Group 2 included 66 patients with Gleason score between 8 and 10, PSA greater than 20 ng/mL, and clinical stage greater than T2b. At a median follow-up of 62.8 months, the 5-year biochemical control (BC) rate, as defined by the American Society for Therapeutic Radiology and Oncology Phoenix Consensus panel statement, was 81% and overall survival was 91%. BC in Groups 1 and 2 were 87% and 71%, respectively. On univariate analysis risk group, pretreatment PSA and age were significant predictors of BC. However, on multivariate analysis only pretreatment PSA was significant. Using the Radiation therapist oncology group criteria, there were 2 (1.5%) cases of grade 3 acute urinary toxicity. Regarding late side effects (n = 5), 4% of patients had grade 3 genitourinary toxicity and no grade 4 complication was observed. External beam radiation therapy and high dose rate brachytherapy for prostate cancer resulted in excellent BC, and overall survival with minimal severe, acute, or late complications.

Efficacy of Androgen Deprivation Therapy in Patients with Clinically Localized Prostate Cancer

Purpose: The purpose of this study was to evaluate the characteristics of patients who received primary androgen deprivation therapy (PADT) for clinically localized prostate cancer and the clinical efficacy of this treatment. Materials and Methods: Between January 1998 and August 2007, patients who underwent PADT for clinically localized prostate adenocarcinoma were analyzed. The patients studied could not receive definitive therapy owing to old age or medical comorbidities. All patients’ Gleason score, pretreatment prostate-specific antigen (PSA) value, time to PSA progression, and D’Amico’s risk criteria were analyzed. Results: A total of 72 patients were analyzed. The patients’ mean age was 75.29 years (range, 57-92 years) and their median pretreatment PSA was 13.52 ng/ml (range, 1.27-74.82 ng/ml). The median follow-up duration was 39 months (range, 18-115 months). Thirteen patients (18.57%) had PSA progression after reaching a PSA nadir. The mean time to PSA progression was 14 months (range, 7-55 months). Among these 13 patients, 2 patients had low-risk prostate cancer and 11 patients had high-risk prostate cancer by D’Amico’s risk criteria. Three of the 13 patients are now receiving chemotherapy, 2 patients died from cancer progression, 3 patients died of a non-cancer cause, and 5 patients are now being conservatively managed. Of the total 72 patients, 70.83% of the patients are still receiving PADT. A total of 11 patients died; however, only 2 deaths were caused by prostate cancer. Conclusions: In patients with localized prostate cancer who could not receive definitive therapy for several reasons, the cancer-caused death rate was very low, even in patients with PSA progression. PADT is an effective therapeutic option in patients with localized prostate cancer. (Korean J Urol 2009;50:1073-1077) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Androgen receptor expression in clinically localized prostate cancer: immunohistochemistry study and literature review

To evaluate androgen receptor (AR) expression in clinically localized prostate cancer (PCa). Specimens were studied from 232 patients who underwent radical prostatectomy for clinically localized prostatic adenocarcinoma without neoadjuvant hormonal therapy or chemotherapy at our institution between November 2001 and June 2005. Immunohistochemical study was performed using an anti-human AR monoclonal antibody AR441. The mean AR density in the hot spots of different histological areas within the same sections were compared and the correlation of malignant epithelial AR density with clinicopathological parameters such as Gleason score, tumor, nodes and metastases (TNM) stage and pre-treatment prostate-specific antigen (PSA) value was assessed. AR immunoreactivity was almost exclusively nuclear and was observed in tumor cells, non-neoplastic glandular epithelial cells and a proportion of peritumoral and interglandular stromal cells. Mean percentage of AR-positive epithelial cells was significantly higher in cancer tissues than that in normal prostate tissues (mean +/- SD, 90.0% +/- 9.3% vs. 85.3 +/- ?9.7%, P < 0.001). The histological score yielded similar results. The percentage of AR immunoreactive prostatic cancer nuclei and histological score were not correlated with existing parameters such as Gleason score, tumor, nodes and metastases stage and pre-treatment PSA value in this surgically treated cohort. The results of the present study suggest that there may be limited clinical use for determining AR expression (if evaluated in hot spots) in men with localized PCa.

Pretreatment prostate-specific antigen velocity is associated with freedom from biochemical recurrence of prostate cancer after low-dose-rate prostate brachytherapy alone

Purpose This report examines the relationship between pretreatment prostate-specific antigen (PSA) velocity (PSAV) and freedom from biochemical recurrence (FFBR) in men with prostate cancer treated with low-dose-rate prostate brachytherapy (LDRPB). Methods and Materials This is a report of 51 men treated with LDRPB between 1997 and 1999. Inclusion criteria: two or more evaluable PSA values >3 months apart and <18 months before treatment. PSAV is calculated using a linear regression equation. All patients had biopsy confirmed, clinically localized prostate cancer. All men were treated with 125I LDRPB. The prescription dose was 144 Gy. Biochemical failure is determined from PSA values over time using the ASTRO Consensus Definition. FFBR is estimated using Kaplan–Meier method. Pretreatment variables analyzed include percentage positive biopsy cores, D 90, risk group, and PSAV. All p values are two-sided. Results The median followup is 60 months. The median pretreatment PSA is 6.5, 75% of men were Stage T1c, and 88% had Gleason score ≥6; 10% developed evidence of biochemical recurrence at a median of 13 months (range, 6–36). The 6-year estimate of FFBR is 90% for the entire cohort. On univariate analysis, pretreatment PSAV and risk group are associated with FFBR. The 6-year estimate of FFBR in patients with a PSAV <2 ng/mL/yr is 100% vs. 80% (95% confidence interval: 64–96%) when the pretreatment PSAV is ≥2 ng/mL/yr before LDRPB ( p = 0.017). Conclusions Pretreatment PSAV is a predictor of FFBR after LDRPB in this population of men with prostate cancer. Men with a pretreatment PSAV ≥2 ng/mL/yr may warrant more aggressive treatment.

12-Year Outcomes Following Permanent Prostate Brachytherapy in Patients with Clinically Localized Prostate Cancer

Purpose We reviewed the outcomes in men treated with permanent prostate brachytherapy (PPB). Material and Methods A total of 1,449 consecutive patients with a mean age of 68 years treated with PPB between 1992 and 2000 and mean pretreatment prostate specific antigen (PSA) 10.1 ng/ml were included in this study. Of the patients 55% presented with Gleason 6 tumors and 28% had Gleason 7 disease. A total of 400 patients (27%) were treated with neoadjuvant hormones and 301 (20%) were treated in combination with external radiation plus PPB. Several biochemical freedom from recurrence (BFR) definitions were determined. Statistical analysis consisted of log rank testing, Kaplan-Meier estimates and Cox regression analysis. Results Median followup was 82 months with 39 patients at risk at for 144 months. Overall and disease specific survival at 12 years was 81% and 93%, respectively. The 12-year BFR was 81%, 78%, 74% and 77% according to the American Society for Therapeutic Radiology and Oncology (ASTRO), ASTRO-Kattan, ASTRO-Last Call and Houston definitions, respectively. The 12-year ASTRO-Kattan BFR using risk stratification was 89%, 78% and 63% in patients at low, intermediate and high risk, respectively (p = 0.0001). Multivariate analysis identified the dose that 90% of the target volume received (p <0.0001), pretreatment PSA (p = 0.001), Gleason score (p = 0.002), the percent positive core biopsies (p = 0.037), clinical stage (p = 0.689), the addition of hormones (p = 0.655) and the addition of external radiation (p = 0.724) for predicting BFR-ASTRO. Five-year disease specific survival was 44% in patients with a PSA doubling time of less than 12 months vs 88% in those with a PSA doubling time of 12 months or greater (p = 0.0001). Conclusions PPB offers acceptable 12-year BFR in patients who present with clinically localized prostate cancer. Implant dosimetry continues as an important predictor for BFR, while the addition of adjuvant therapies such as hormones and external radiation are insignificant. In patients who experience biochemical failure it appears that PSA doubling time is an important predictor of survival.

Does Transurethral Resection of Prostate (TURP) Affect Outcome in Patients Who Subsequently Develop Prostate Cancer?

Pretreatment prostate specific antigen (PSA) is a strong predictor of prostate cancer outcome after radiotherapy and is a key parameter in pretreatment risk assessment. Because PSA is secreted from both benign and malignant tissue, a prior transurethral resection of prostate (TURP) may lower pretreatment PSA levels out of proportion to the extent of cancer. The purpose of this study was to determine whether a history of TURP is associated with increased biochemical failure (BF) after definitive radiotherapy for prostate cancer. From April 1989 to October 2001, 1135 men with low to intermediate risk T1c-2NX/0M0 (2002 AJCC) prostate cancer with a pretreatment PSA less than 20 ng/mL received three-dimensional conformal radiotherapy (median dose, 76 Gy) without androgen deprivation. The median pretreatment PSA was 7.4 ng/mL (range, 0.4 to 19.9). There were 126 men with a prior history of TURP. The Cox proportional hazards model was used for univariate and multivariate analyses for BF (nadir + 2 ng/mL definition). On multivariable analysis, Gleason score (GS), PSA, and T-stage were significant predictors of BF in a model containing TURP and dose. A history of TURP was not a significant independent predictor of BF on subgroup analysis. There was a trend toward significance for the subgroup of GS less than 7 (P = 0.12). A history of prior TURP does not affect outcome after RT for prostate cancer in low to intermediate risk patients.

Does a delay in initiating definitive therapy affect biochemical recurrence rates in men with clinically localized prostate cancer?

Purpose To assess whether a delay in initiating definitive therapy for clinically localized prostate cancer affects outcome. Methods We retrospectively reviewed 393 men with localized prostate cancer treated with radiation therapy or surgery without systemic therapy between 1991 and 2004. Data included: time from diagnosis to treatment initiation (more or less than 3 months); biopsy Gleason score grouped by low (2–6), intermediate (7), or high risk (8–10); clinical stage grouped by low (T1/T2a) or high risk (T2b or higher); pretreatment prostate-specific antigen (PSA) grouped by low (<10 ng/ml), intermediate (10–20), or high risk (>20); and biochemical recurrence-free survival. Results Median patient age was 63.1 years (range 39.7–79.5). Median pretreatment PSA was 6.5 ng/ml (range 0.4–411). Median time from diagnosis to treatment was 57 days (range 8–2927). A total of 310 patients (79%) were treated within 3 months. Median follow-up was 2.3 years (range 0.1–14.0). On univariate analysis using Kaplan-Meier survival curves and the log-rank test, only pretreatment PSA was associated with worse biochemical recurrence-free survival ( P = 0.008). Biochemical recurrence-free survival was not associated with time from diagnosis to treatment ( P = 0.28), clinical stage ( P = 0.50), or biopsy Gleason score ( P = 0.19). The results were the same when analyzed in a multivariable analysis using the Cox proportional hazards model. Conclusion A delay in treatment of ≥3 months does not appear to affect adversely biochemical recurrence-free survival in patients who undergo definitive therapy for clinically localized prostate cancer in those with low risk features.

Prediagnostic Prostate-Specific Antigen Velocity and Probability of Detecting High-Grade Prostate Cancer

Men with high-grade prostate cancer experience a survival benefit when androgen suppression therapy is combined with radiotherapy (RT) compared with RT alone. We evaluated whether an association exists between the pretreatment prostate-specific antigen (PSA) velocity and high-grade prostate cancer at diagnosis, controlling for known predictors of high-grade disease. The study cohort consisted of 358 men with Stage T1c-T4 prostate cancer treated with external beam RT from 1989 to 2002. Univariate and multivariate logistic regression analyses were used to assess whether an association exists between the pretreatment PSA velocity, PSA level, age, clinical T stage, and Gleason score 4+3 or greater compared with Gleason score 3+4 or less prostate cancer. Of the 358 men, 73 had a Gleason score of 4+3 or greater. The median PSA velocity was 2.71 ng/mL/yr (interquartile range 1.09 to 12.6) for men with a Gleason score of 4+3 or greater and 1.24 ng/mL/yr (interquartile range 0.71 to 3.37) for men with a Gleason score of 3+4 or less. All clinical covariates were significantly associated (P < or = 0.05) with a Gleason score of 4+3 or greater on univariate analysis. On multivariate analysis, the PSA velocity (odds ratio 1.06, 95% confidence interval 1.02 to 1.10, P = 0.004), age (odds ratio 1.07, 95% confidence interval 1.02 to 1.13, P = 0.008), and clinical T stage (odds ratio 2.17, 95% confidence interval 1.21 to 3.92, P = 0.01) were significantly associated with the detection of Gleason score 4+3 or greater prostate cancer. The prediagnostic PSA velocity, patient age, and clinical T stage were significantly associated with high-grade prostate cancer at diagnosis. Because a biopsy Gleason score of 4+3 or greater is associated with a prostatectomy Gleason score of 7 or greater in the vast majority of cases, these parameters can identify men at high risk of harboring occult high-grade prostate cancer, permitting improved selection of RT fields and the use of androgen suppression therapy.

Efficacy of primary hormonal therapy for patients with localized and locally advanced prostate cancer: A retrospective multicenter study

A retrospective review of patients with localized and locally advanced prostate cancer was performed to evaluate the efficacy of primary hormonal therapy and predict long-term prognosis in these patients. A total of 628 patients who were diagnosed with stage T1c to T3 prostate cancer were treated with primary hormonal therapy at participating institutions. The patients were classified based on pretreatment prostate-specific antigen (PSA) level, Gleason score, and time to nadir PSA level. Disease-specific and progression-free survival rates were investigated, and compared among the subgroups. The mean age of patients was 74.5 years, and median pretreatment PSA level was 14.0 ng/mL. A total of 399 patients (63.5%) were treated with combined androgen blockade (CAB), and 229 patients (36.5%) were treated with castration monotherapy. The disease-specific survival rate of all 628 patients was 89.1% at 8 years. The group that showed a good response to primary hormonal therapy (Group G, pretreatment PSA level < or =20 ng/mL, Gleason score < or =7, and time to nadir PSA < or =6 months) accounted for approximately one-third of the total number of T1c-T3 patients. Disease-specific and progression-free survival rates at 8 years in Group G were 98.9% and 82.0%, respectively. These rates increased to 100% and 87.3%, respectively, in patients receiving CAB treatment in Group G. The results indicate the usefulness of primary hormonal therapy, especially CAB treatment, for patients showing a good response to hormonal therapy in long-term control of localized and locally advanced prostate cancer.

Long-Term Results in Three-Dimensional Conformal Radiotherapy of Localized Prostate Cancer at Moderate Dose (66 Gy)

Biochemical control (bNED), disease-specific survival (DSS), overall survival (OS), and late gastrointestinal (GI) and urogenital (UG) side effects (EORTC/RTOG) of patients with long-term follow-up were evaluated. Three-dimensional radiotherapy up to 66 Gy with/without additional hormonal therapy was performed in 154 prostate cancer (T1-3 N0 M0) patients. According to T-stage, pretreatment prostate-specific antigen (PSA) and grading, patients were divided into a low-, intermediate-, and high-risk group. The 5-, 8-, and 10-year actuarial rates of bNED, DSS and OS and late side effects were calculated. Median follow-up was 80 months. Additional hormonal therapy was given in 57% of patients. Distribution concerning risk groups (low, intermediate, high) showed 15%, 49%, and 36% of patients, respectively. bNED 5-, 8-, and 10-year actuarial rates were 46%, 44%, and 44%. DSS 5-, 8- and 10-year rates amounted to 96%, 90%, and 82%. OS 5-, 8- and 10-year rates were 81%, 64%, and 56%. In uni- and multivariate analysis, only pretreatment PSA (<10 vs. >or=10 ng/ml; p<0.05) and PSA nadir (<0.5 vs. >or=0.5 ng/ml; p<0.0001) affected bNED significantly. Age, risk group, T-stage, grading, and hormonal therapy had no significant influence on bNED, DSS, and OS. Rates of late GI and UG side effects grade>or=2 at 5 years were 17% and 15%. Current dose escalation studies with better bNED rates may be able to further increase long-term clinical outcome.

High-dose radiation employing external beam radiotherapy and high-dose rate brachytherapy with and without neoadjuvant androgen deprivation for prostate cancer patients with intermediate- and high-risk features

The role of neoadjuvant androgen deprivation (NAD) in high-risk prostate cancer patients receiving high-dose radiotherapy (RT) remains unstudied. To evaluate the effect of a course of NAD, we reviewed the experiences of three institutions treating these patients with combined RT and high-dose rate brachytherapy (HDR). Of 1260 prostate cancer patients with high-risk features (pretreatment prostate-specific antigen (PSA) > or =10, Gleason Score (GS) > or =7, or T stage > or =T2b), 560 received no NAD (n=308) or NAD for < or =6 months (n=252). Median dose to the prostate from RT and HDR was 42 and 23 Gy, respectively. Average total biologic equivalent prostate dose was >100 Gy (alpha/beta=1.2). Median follow-up was 4.3 years. Pretreatment characteristics were similar on chi(2) tables for all 560 patients treated with or without NAD including pretreatment PSA (P=0.11), GS (P=0.4), and clinical T stage (P=0.2). Outcomes worsened for patients receiving NAD (5-year distant metastasis (DM) 10 vs 5% (P=0.04); cause-specific survival (CSS), 93 vs 98% (P=0.005)). Higher 5-year DM rates and lower CSS occurred in NAD patients with a GS between 8 and 10 (n=112 (P=0.03, P=0.02)), pretreatment PSA> or =15 (n=136 (P=0.03, P=0.008)), and palpable disease > or =T2a (n=434 (P=0.04, P=0.02)). The only two significant risk factors for DM on Cox multivariate analysis were GS (P=0.003, HR 2.8) and NAD (P=0.03, HR 2.7). AD given before definitive high-dose RT did not benefit prostate cancer patients with intermediate- and high-risk features. We favor the use of concurrent/adjuvant AD over prolonged NAD for prostate cancer patients for whom AD is clinically indicated.

Five years experience of transrectal high‐intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer

High-intensity focused ultrasound (HIFU) is a minimally invasive technique used in achieve coagulation necrosis. We evaluated biochemical disease-free survival rates, predictors of clinical outcome and morbidity in patients with localized prostate cancer treated with HIFU. A total of 181 consecutive patients underwent HIFU with the use of Sonablate (Focus Surgery, Indianapolis, IN, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and pretreatment prostate-specific antigen (PSA) level were 70 years (range 44-88) and 9.76 ng/mL (range 3.39-89.60). A total of 95 patients (52%) were treated with neoadjuvant hormones. The median follow-up period for all patients was 18.0 months (range 4-68). The biochemical disease-free survival rates at 1, 3 and 5 years in all patients were 84%, 80% and 78%, respectively. The biochemical disease-free survival rates at 3 years for patients with pretreatment PSA less than 10 ng/mL, 10.01-20.0 ng/mL and more than 20.0 ng/mL were 94%, 75% and 35%, respectively (P<0.0001). Multivariate analysis identified pretreatment PSA (P<0.0001) as a independent predictor of relapse. High-intensity focused ultrasound therapy appears to be a safe and efficacious minimally invasive therapy for patients with localized prostate cancer, especially those with a pretreatment PSA level less than 20 ng/mL.

Race and survival of men treated for prostate cancer on radiation therapy oncology group phase III randomized trials.

We assessed the impact of race on survival in men treated with external beam radiotherapy with or without hormonal therapy for localized prostate cancer in Radiation Therapy Oncology Group randomized trials. Between 1975 and 1992, 2,048 men were treated for clinically localized prostate cancer in 1 of 4 consecutive prospective phase III randomized trials. After excluding nonblack and nonwhite men 2,012 remained for analysis. Patients were included in this analysis if they were deemed evaluable and eligible for the trial, and followup information and centrally reviewed pathological results were available. Short-term hormonal therapy consisted of goserelin acetate and flutamide administered 2 months before and during radiotherapy. Long-term hormonal therapy consisted of adjuvant goserelin acetate, which was generally given for 2 years or more. Pretreatment prostate specific antigen (PSA) findings were available in 430 cases (21%), including 213 treated with radiotherapy alone, 60 treated with short-term hormonal therapy and 157 on long-term hormonal therapy. Mean pretreatment PSA was 68.8 and 35.2 ng./ml. in black and white patients, respectively. Cox proportional hazards models were used to identify the impact of previously defined risk groups on overall and disease specific survival. Multivariate analysis was done for the significance of race using a stratified Cox model. Median followup in patients treated in early and late studies exceeded 11 and 6 years, respectively. On univariate analysis black race was associated with lower overall and disease specific survival (p = 0.04, RR = 1.24 and p = 0.016, RR = 1.41, respectively). After adjusting for risk group and treatment type (with or without short-term or long-term hormonal therapy) race was no longer associated with outcome (p >0.05). The trend for a persistent difference in survival was likely due to the higher tumor burden in black men, as reflected in higher PSA. As previously reported, tumor grade (Gleason score), palpation T stage, lymph node status, pretreatment PSA and treatment type are major predictors of overall and disease specific survival. We noted no evidence that race has independent prognostic significance in patients treated for prostate cancer in Radiation Therapy Oncology Group prospective randomized trials.

12-YEAR OUTCOMES FOLLOWING PERMANENT PROSTATE BRACHYTHERAPY IN PATIENTS WITH CLINICALLY LOCALIZED PROSTATE CANCER

We reviewed the outcomes in men treated with permanent prostate brachytherapy (PPB). A total of 1,449 consecutive patients with a mean age of 68 years treated with PPB between 1992 and 2000 and mean pretreatment prostate specific antigen (PSA) 10.1 ng/ml were included in this study. Of the patients 55% presented with Gleason 6 tumors and 28% had Gleason 7 disease. A total of 400 patients (27%) were treated with neoadjuvant hormones and 301 (20%) were treated in combination with external radiation plus PPB. Several biochemical freedom from recurrence (BFR) definitions were determined. Statistical analysis consisted of log rank testing, Kaplan-Meier estimates and Cox regression analysis. Median followup was 82 months with 39 patients at risk at for 144 months. Overall and disease specific survival at 12 years was 81% and 93%, respectively. The 12-year BFR was 81%, 78%, 74% and 77% according to the American Society for Therapeutic Radiology and Oncology (ASTRO), ASTRO-Kattan, ASTRO-Last Call and Houston definitions, respectively. The 12-year ASTRO-Kattan BFR using risk stratification was 89%, 78% and 63% in patients at low, intermediate and high risk, respectively (p = 0.0001). Multivariate analysis identified the dose that 90% of the target volume received (p <0.0001), pretreatment PSA (p = 0.001), Gleason score (p = 0.002), the percent positive core biopsies (p = 0.037), clinical stage (p = 0.689), the addition of hormones (p = 0.655) and the addition of external radiation (p = 0.724) for predicting BFR-ASTRO. Five-year disease specific survival was 44% in patients with a PSA doubling time of less than 12 months vs 88% in those with a PSA doubling time of 12 months or greater (p = 0.0001). PPB offers acceptable 12-year BFR in patients who present with clinically localized prostate cancer. Implant dosimetry continues as an important predictor for BFR, while the addition of adjuvant therapies such as hormones and external radiation are insignificant. In patients who experience biochemical failure it appears that PSA doubling time is an important predictor of survival.

Permanent Interstitial Brachytherapy for Clinically Organ-Confined High-Grade Prostate Cancer With a Pretreatment PSA &lt; 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.

10-YEAR DISEASE-FREE SURVIVAL RATES AFTER SIMULTANEOUS IRRADIATION FOR PROSTATE CANCER WITH A FOCUS ON CALCULATION METHODOLOGY

We documented the 10-year disease-free survival rate after simultaneous irradiation for prostate cancer and suggested standards for outcome calculation methodology. From 1992 to 1998, 1,469 consecutive men with clinical stage T1T2NxM0 prostate cancer who did not receive neoadjuvant hormones were treated with simultaneous irradiation, an ultrasound guided transperineal prostate I seed implant followed by external irradiation. Median pretreatment prostate specific antigen (PSA) was 7.1 ng/ml (range 0.3 to 88). All men were treated 5 or more years ago. Median followup was 6 years (range 3 months to 11 years). Disease freedom was defined as the achievement and maintenance of PSA 0.2 ng/ml or less, and treatment failure was defined as a PSA nadir greater than 0.2 ng/ml or a subsequent PSA increase above this level. The overall 10-year disease-free survival rate was 83%. Median time to recurrence was 30 months (range 3 months to 8 years) and 24% of recurrences were after 5-year followup. The 10-year outcome according to low, intermediate and high risk group was 93%, 80% and 61%, respectively (p <0.0001). Multivariate analysis of factors related to disease freedom documents that pretreatment PSA, Gleason score and percent positive biopsies were significant but stage and age were not. By calculating outcome with PSA cut point 0.2 ng/ml and evaluation only of men treated 5 or more years ago, the 10-year disease-free survival rates from this study can be reasonably compared with the outcome of radical prostatectomy performed in the PSA era.

A Preoperative Nomogram Identifying Decreased Risk of Positive Pelvic Lymph Nodes in Patients With Prostate Cancer

We developed a preoperative nomogram for prediction of lymph node metastases in patients with clinically localized prostate cancer. The study was a retrospective, nonrandomized analysis of 7,014 patients treated with radical prostatectomy at 6 institutions between 1985 and 2000. Exclusion criteria consisted of preoperative androgen ablation therapy, salvage radical prostatectomy and pretreatment prostate specific antigen (PSA) greater than 50 ng/ml. Preoperative predictors of lymph node metastases consisted of pretreatment PSA, clinical stage (1992 TNM) and biopsy Gleason sum. These predictors were used in logistic regression analysis based nomograms to predict the probability of lymph node metastases. Overall 5,510 patients with complete clinical and pathological information were included in the study. Lymph nodes metastases were present in 206 patients (3.7%). Pretreatment PSA, biopsy Gleason sum, clinical stage and institution represented predictors of lymph node status (p <0.001). Bootstrap corrected predictive accuracy of the 3-variable nomogram (clinical stage, Gleason sum and PSA) was 0.76. Inclusion of a fourth variable, which accounts for institutional differences in lymph node metastases, yielded an area under the receiver operating characteristics curve of 0.78. The negative predictive value of our nomograms was 0.99 when they predicted 3% or less chance of positive lymph nodes. Using clinical information, we produced 2 calibrated and validated nomograms, which accurately predict pathologically negative lymph nodes in men with localized prostate cancer who are candidates for radical prostatectomy.

The 1999 patterns of care study of radiotherapy in localized prostate carcinoma

The objective of the current study was to provide descriptive information on a representative national sample of patients with prostate carcinoma who were treated with prostate brachytherapy (PB) in calendar year 1999. A random survey was conducted by the Patterns of Care Study in radiation oncology of 59 facilities (1 facility had no eligible patients) that treated patients with prostate carcinoma in 1999 in the United States. A weighted sample size of 36,496 patients with prostate cancer was included in the 1999 survey (unweighted sample size, 554 patients). The main measures were the clinical characteristics of men prior to treatment and the technical characteristics of PB. Patients were classified into three prognostic groups according to T stage, pretreatment prostate specific antigen (PSA) level, and Gleason score. A weighted sample size of 13,293 patients (36%; unweighted sample size, 162 patients) was treated with PB. Compared with a weighted sample size of 23,203 patients (64%; unweighted sample size, 392 patients) was treated with external beam radiotherapy (EB), patients who received PB were significantly younger (mean age: PB group, 67.7 years; EB group, 70.8 years; P = 0.0006). The mean pretreatment PSA level for the PB group was lower compared with the EB group (9.9 ng/mL vs. 13.33 ng/mL; P = 0.0015). The prognostic groupings were more favorable for patients in the PB group compared with patients in EB group (P = 0.0365). The utilization of androgen deprivation therapy (ADT) in the PB group was similar to the utilization of ADT in the EB group (40.4% vs. 51.3%; P = 0.2282). The vast majority of men who were treated with PB received low-dose-rate, permanent sources (89%). Fifty-four percent of men received PB monotherapy (PBM), and the remaining 46% were treated with EB in addition to PB (EBPB). The prognostic groupings were more favorable for patients in the PBM group compared with patients in the EBPB group (P = 0.0037). Of the men who were treated with low-dose-rate PB, 59% were treated with iodine-125 (I-125), and 41% were treated with palladium-103 (Pd-103). I-125 was used more frequently in men who were treated with PBM, and Pd-103 was used more frequently in men who were treated with EBPB. Postimplantation dosimetry was documented in 61.0% of men who were treated with low-dose-rate PB. Computed tomography imaging was used for 46.5% of men. PB was used in 36% of men who were treated with radiotherapy nationally. The mean age of men who were treated with PB was younger than the population of men who were treated with EB alone. Nearly 50% of men who received PB also received EB. EB was used more frequently in men with higher-risk disease. ADT was used in 40% of patients in the PB group. Techniques and prescription doses were consistent with published guidelines.

Age and PSA predict likelihood of organ-confined disease in men presenting with PSA less than 10 ng/mL: implications for screening

Objectives To examine age and pretreatment prostate-specific antigen (PSA) level as predictors of organ-confined disease in a large multinational database of men with pretreatment PSA levels less than 10 ng/mL who were treated with radical prostatectomy. The optimal PSA and age cutoffs for triggering prostate biopsy are controversial. Although a PSA level greater than 4.0 ng/mL is generally accepted, recent observations suggest that PSA values between 2.5 and 4.0 ng/mL are associated with a 20% detection rate. Furthermore, age has been shown to represent an independent predictor of outcome after radical prostatectomy. Methods We analyzed a cohort of 3198 patients from five institutions, who underwent radical prostatectomy between 1985 and 2001 for clinically localized prostate cancer. All presented with a pretreatment PSA level of less than 10 ng/mL. Multivariate analyses addressed age, preoperative PSA, year of treatment, biopsy Gleason sum, and clinical stage as independent predictors of non-organ-confined disease (NOCD). Results Twenty-nine percent of patients had NOCD. All tested variables were independent, multivariate predictors of NOCD (age, P = 0.004; year of treatment, P <0.0001; PSA, P <0.0001; Gleason sum, P <0.0001; clinical stage, P <0.0001). A linear relationship between age and the risk of NOCD was noted. The likelihood of NOCD remained constant for PSA levels between 0.1 and 4.0 ng/mL and rose substantially for PSA levels greater than 4.0 ng/mL. Conclusions After controlling for other covariates, the rate of NOCD increased in proportion to age and pretreatment PSA level in men initially diagnosed with a serum PSA level less than 10 ng/mL. These observations suggest that younger men with a lower PSA are more likely to have organ-confined and curable disease at diagnosis. This information has important implications for counseling and screening.

Using the percentage of biopsy cores positive for cancer, pretreatment PSA, and highest biopsy Gleason sum to predict pathologic stage after radical prostatectomy: the center for prostate disease research nomograms

Objectives To develop probability nomograms to predict pathologic outcome at the time of radical prostatectomy (RP) on the basis of established prognostic factors and prostate biopsy quantitative histology. Methods Using information from the database of the Center for Prostate Disease Research (CPDR), univariate and multivariate analyses were performed on 1510 men who had undergone transrectal ultrasound and biopsy for diagnosis and had radical prostatectomy as primary therapy, with variables of age, race, clinical stage, pretreatment prostate-specific antigen (PSA), biopsy Gleason sum, and percentage of biopsy cores positive for cancer (total number of cores positive for cancer divided by the total number of cores obtained). The percentages of biopsy cores positive were grouped as less than 30%, 30% to 59%, and greater than or equal to 60%. The three most significant variables were used to develop probability nomograms for pathologic stage. Results PSA, biopsy Gleason sum, and percentage of cores positive were the three most significant independent predictors of pathologic stage. The assigned percentage of biopsy core-positive subgroups along with pretreatment PSA and highest Gleason sum were used to develop probability nomograms for pathologic stage. Conclusions Pretreatment PSA, highest biopsy Gleason sum, and the percentage of cores positive for cancer are the most significant predictors for pathologic stage after radical prostatectomy. On the basis of these findings, CPDR probability nomograms were developed to predict pathologic outcome at the time of RP.