Median Posttreatment Prostate-specific Antigen Research Articles

Posttreatment Prostate-Specific Antigen 6 Months After Radiation With Androgen Deprivation Therapy Predicts for Distant Metastasis–Free Survival and Prostate Cancer–Specific Mortality

To determine whether a 6-month posttreatment prostate-specific antigen (PSA) value in patients with prostate cancer (PCa) treated with concurrent androgen deprivation therapy (ADT) and external beam radiation therapy (EBRT) serves as an early predictor for biochemical relapse free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM). A retrospective review of intermediate-risk and high-risk PCa patients treated with EBRT and concurrent ADT at a single institution between 1996 and 2012. All patients received high-dose radiation with either 78Gy in 39 fractions or 70Gy in 28 fractions. Kaplan-Meier analysis was used to estimate bRFS and DMFS, and cumulative incidence was used to estimate PCSM. 532 patients were identified. The median follow-up time was 7.5years (range, 1-16.25years). The median initial PSA (iPSA) was 13.0ng/mL (range, 0.37-255ng/mL), and the median duration of ADT was 6months (range, 1-78months). The median PSA 6months after EBRT was 0.1ng/mL (range, 0-19ng/mL), and 310 patients (58.3%) had a 6-month PSA ≤0.1ng/mL. Multivariable analysis (MVA) demonstrated that a 6-month post-EBRT PSA of >0.1ng/mL was an independent predictor of worse bRFS (hazard ratio [HR]=2.518; P<.0001), DMFS (HR=3.743; P<.0001), and PCSM (HR=5.435; P<.0001). On MVA, a Gleason score of 8 to 10 also correlated with worse DMFS and PCSM (P<.05). The duration of ADT (1-6 vs >6months) was not predictive of any clinical endpoint. A 6-month posttreatment PSA >0.1ng/mL in intermediate-risk and high-risk PCa patients treated with concurrent high-dose EBRT and ADT is associated with worse bRFS, DMFS, and PCSM. The duration of ADT was not predictive of any clinical endpoint. A 6-month PSA after definitive EBRT and ADT helps identify patients at higher risk of disease progression and may serve as a predictive tool to select patients for early salvage therapy on future clinical trials.

High-Risk Prostate Cancer With Gleason Score 8–10 and PSA Level ≤15 ng/ mL Treated With Permanent Interstitial Brachytherapy

With widespread prostate-specific antigen (PSA) screening, there has been an increase in men diagnosed with high-risk prostate cancer defined by a Gleason score (GS) ≥8 coupled with a relatively low PSA level. The optimal management of these patients has not been defined. Cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) were evaluated in brachytherapy patients with a GS ≥8 and a PSA level ≤15 ng/mL with or without androgen-deprivation therapy (ADT). From April 1995 to October 2005, 174 patients with GS ≥8 and a PSA level ≤15 ng/mL underwent permanent interstitial brachytherapy. Of the patients, 159 (91%) received supplemental external beam radiation, and 113 (64.9%) received ADT. The median follow-up was 6.6 years. The median postimplant Day 0 minimum percentage of the dose covering 90% of the target volume was 121.1% of prescription dose. Biochemical control was defined as a PSA level ≤0.40 ng/mL after nadir. Multiple parameters were evaluated for impact on survival. Ten-year outcomes for patients without and with ADT were 95.2% and 92.5%, respectively, for CSS (p = 0.562); 86.5% and 92.6%, respectively, for bPFS (p = 0.204); and 75.2% and 66.0%, respectively, for OS (p = 0.179). The median post-treatment PSA level for biochemically controlled patients was <0.02 ng/mL. Multivariate analysis failed to identify any predictors for CSS, whereas bPFS and OS were most closely related to patient age. Patients with GS ≥8 and PSA level ≤15 ng/mL have excellent bPFS and CSS after brachytherapy with supplemental external beam radiotherapy. The use of ADT did not significantly impact bPFS, CSS, or OS.

Long-Term Outcome for Clinically Localized Prostate Cancer Treated With Permanent Interstitial Brachytherapy

To present the largest series of prostate cancer brachytherapy patients treated with modern brachytherapy techniques and postimplant day 0 dosimetric evaluation. Between April 1995 and July 2006, 1,656 consecutive patients were treated with permanent interstitial brachytherapy. Risk group stratification was carried out according to the Mt. Sinai guidelines. Median follow-up was 7.0 years. The median day 0 minimum dose covering at least 90% of the target volume was 118.8% of the prescription dose. Cause of death was determined for each deceased patient. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on the evaluated survival parameters. At 12 years, biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) for the entire cohort was 95.6%, 98.2%, and 72.6%, respectively. For low-, intermediate-, and high-risk patients, bPFS was 98.6%, 96.5%, and 90.5%; CSS was 99.8%, 99.3%, and 95.2%; and OS was 77.5%, 71.1%, and 69.2%, respectively. For biochemically controlled patients, the median posttreatment prostate-specific antigen (PSA) concentration was 0.02 ng/ml. bPFS was most closely related to percent positive biopsy specimens and risk group, while Gleason score was the strongest predictor of CSS. OS was best predicted by patient age, hypertension, diabetes, and tobacco use. At 12 years, biochemical failure and cause-specific mortality were 1.8% and 0.2%, 5.1% and 2.1%, and 10.4% and 7.1% for Gleason scores 5 to 6 and 7 and ≥8, respectively. Excellent long-term outcomes are achievable with high-quality brachytherapy for low-, intermediate-, and high-risk patients. These results compare favorably to alternative treatment modalities including radical prostatectomy.

Brachytherapy or Conformal External Radiotherapy for Prostate Cancer: A Single-Institution Matched-Pair Analysis

In the absence of randomized study data, institutional case series have shown brachytherapy (BT) to produce excellent biochemical control (bNED) in patients with localized prostate cancer compared with alternative curative treatments. This study was designed to overcome some of the limitations of case series studies by using a matched-pair design in patients treated contemporaneously with BT and external beam radiation therapy (EBRT) at a single institution. Six hundred one eligible patients treated between 1998 and 2001 were prospectively followed up in our institutional databases and matched on a 1:1 basis for the following known prognostic variables: prostate-specific antigen (PSA) level, Gleason score, T stage, the use and duration of neoadjuvant androgen deprivation therapy, and the percentage of positive tissue core samples. Two hundred seventy-eight perfect matches of patients (139 in each group) with low- and intermediate-risk cancer were further analyzed. bNED (Phoenix definition) was the primary endpoint. Other endpoints were toxicity, PSA kinetics, and the secondary use of androgen deprivation therapy. The 5-year bNED rates were 95% (BT) and 85% (EBRT) (p < 0.001). After 7 years, the BT bNED result was unchanged, but the rate in EBRT patients had fallen to 75%. The median posttreatment PSA nadirs were 0.04 ng/mL (BT) and 0.62 ng/mL (EBRT, p < 0.001), which predicted a higher ongoing treatment failure rate in association with EBRT use than with BT use. Late urinary toxicity and rectal/bowel toxicity were worse in patients treated with BT and EBRT, respectively. BT for both low-risk and selected intermediate-risk cancers achieves exceptional cure rates. Even with dose escalation, it will be difficult for EBRT to match the proven track record of BT seen over the past decade.

Determining Dosing Intervals for Luteinizing Hormone Releasing Hormone Agonists Based on Serum Testosterone Levels: A Prospective Study

Long acting luteinizing hormone releasing hormone agonists are the predominant form of androgen suppression in the treatment of prostate cancer with the goal of maintaining castrate levels of testosterone. Current dosing of luteinizing hormone releasing hormone agonists does not include monitoring the end organ response of serum testosterone. Recent evidence suggests standard dosing regimens fail to achieve castrate levels of testosterone in some patients while in other patients testosterone can remain at castrate levels longer than the manufacturer recommended dosing interval. We prospectively evaluated patients with prostate cancer receiving luteinizing hormone releasing hormone agonist hormonal therapy to determine the length of time that serum testosterone remains at or below castrate levels. A 3-month dose of 22.5 mg leuprolide was administered to all patients as a first dose followed by a second dose 3 months later. Serum testosterone and prostate specific antigen were measured prospectively before starting hormonal therapy, after the first dose (12 weeks) and again following the second dose (24 weeks) to assess if castrate levels of testosterone (50 ng/dl or less) had been reached. At 24 weeks if patient serum testosterone was 50 ng/dl or less, then 22.5 mg leuprolide were not administered, and serum testosterone and prostate specific antigen were checked monthly. When serum testosterone was greater than 50 ng/dl a subsequent dose of 22.5 mg leuprolide was given. Serum testosterone and prostate specific antigen were then checked 3 months later and monthly thereafter until testosterone was greater than 50 ng/dl. Thus, the time that testosterone remained at castrate levels could be accurately established. From February 2003 to August 2005, 42 patients were treated in this manner with a median followup of 18 months (range 10 to 30). Average patient age was 77 years. Median Gleason grade was 7 (range 6 to 9). Median pretreatment prostate specific antigen was 15.1 ng/ml (range 0.6 to 433) and median posttreatment prostate specific antigen was 0.74 (less than 0.1 to 120). The median dosing interval was 6 months (range 5 to 12). Three patients had an increase in prostate specific antigen while receiving treatment despite castrate levels of testosterone. No patient required more frequent dosing than every 5 months. Testosterone based luteinizing hormone releasing hormone agonist therapy makes empirical sense. It represents continuous androgen ablation based on the patient physiological end point, namely testosterone. Early data suggest that using serum testosterone to guide luteinizing hormone releasing hormone dosing is safe, efficacious and cost-effective. By following end organ response, patients receive individualized care and more accurate androgen suppression therapy.

Prognostic significance of perineural invasion on biochemical progression-free survival after prostate brachytherapy

Objectives To evaluate the influence of perineural invasion (PNI) in the biopsy specimen on biochemical progression-free survival in hormone-naive patients with prostate cancer undergoing brachytherapy. Methods A total of 512 consecutive hormone-naive patients (173 low risk, 212 intermediate risk, and 127 high risk) underwent brachytherapy for clinical Stage T1b-T2cNxM0 (2002 American Joint Committee on Cancer staging system) prostate cancer. No patient underwent seminal vesicle or pathologic lymph node staging. All patients had undergone brachytherapy at least 3 years before analysis. The median follow-up was 5.3 years. Biochemical progression-free survival was defined by a prostate-specific antigen (PSA) cutpoint of 0.4 ng/mL or less after nadir and by the American Society for Therapeutic Radiology and Oncology consensus definition. PNI was defined as carcinoma tracking along, or around, a nerve within the perineural space. Results PNI was documented in 133 patients (26.0%). For both biochemical progression-free definitions, 94.0% and 94.9% of patients with and without PNI, respectively, remained free of biochemical progression. The median time to failure in patients with and without PNI was 17.2 and 17.9 months, respectively. For the biochemically disease-free cohort, the median posttreatment PSA level was less than 0.1 ng/mL. On univariate Cox regression analysis, the pretreatment PSA level, percentage of positive biopsies, prostate volume, and Gleason score predicted for biochemical outcome. PNI did not approach statistical significance ( P = 0.671). On multivariate analysis, only pretreatment PSA ( P <0.001) and the percentage of positive biopsies ( P <0.001) maintained statistical significance. Conclusions In hormone-naive brachytherapy patients implanted with generous periprostatic treatment margins, the presence of PNI in the biopsy specimen did not adversely affect 8-year biochemical progression-free survival.

The Impact of Primary Gleason Grade on Biochemical Outcome Following Brachytherapy for Hormone-Naive Gleason Score 7 Prostate Cancer

Although the perception exists that biochemical outcome in patients with a Gleason score of 7 with dominant pattern 4 histology is inferior to that of patients with a Gleason score of 7 with a primary Gleason grade of 3, conflicting conclusions have been reported for radical prostatectomy and brachytherapy. In this study, we evaluate the effect of the dominant histologic pattern in Gleason score 7 prostate cancer on biochemical progression-free survival after brachytherapy. Between April 1995 and October 2001, 273 consecutive patients underwent permanent interstitial brachytherapy without androgen deprivation therapy for clinical T1c-T3a NxM0 (2002 American Joint Committee on Cancer) prostate cancer. No patient underwent seminal vesicle biopsy or pathological lymph node staging. All patients underwent brachytherapy more than 3 years before analysis. Biochemical progression-free survival was defined by a prostate specific antigen (PSA) cut point < or = 0.4 ng/mL after nadir or by the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus definition. The median follow-up was 4.7 years. Clinical, treatment, and dosimetric parameters evaluated for biochemical progression-free survival included primary Gleason grade; clinical T stage; pretreatment PSA level; risk group; percent positive biopsy results; perineural invasion; patient age; isotope; supplemental external-beam radiation therapy; prostate volume; brachytherapy planning volume; percent of the target volume receiving 100%, 150%, and 200% of the prescribed dose (V100/150/200); minimum percent of the prescribed dose covering 90% of the target volume (D90); tobacco consumption; hypertension; and diabetes. For the entire cohort, the actuarial 8-year biochemical progression-free survival rate was 94.5% and 94.8% using a PSA cut point < or = 0.4 ng/mL after nadir and the ASTRO consensus definition, respectively. For biochemically disease free patients, the median posttreatment PSA level was < 0.1 ng/mL. When the group was stratified by the dominant histologic pattern, no statistical difference in outcome was noted for any of the evaluated parameters. In forward conditional Cox regression analysis, pretreatment PSA level and percent positive biopsy results were statistically significant predictors of biochemical outcome. In hormone-naive patients with a Gleason score of 7, prostate brachytherapy results in a high probability of 8-year biochemical progression-free survival and is independent of Gleason 3 + 4 versus 4 + 3 histology.

Influence of body mass index on biochemical outcome after permanent prostate brachytherapy

To evaluate the impact of body mass index (BMI) on the 8-year biochemical outcome after permanent prostate brachytherapy with or without the addition of supplemental external beam radiotherapy and/or androgen deprivation therapy (ADT). From April 1995 through February 2001, 686 consecutive patients underwent brachytherapy using either palladium-103 or iodine-125 for clinical Stage T1b-T3aNxM0 (2002 American Joint Committee on Cancer) prostate cancer. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. The median follow-up was 59.5 months. The evaluated BMI subgroups were less than 25, 25.0 to 29.9, 30.0 to 34.9, and 35 or more kg/m2. Biochemical progression-free survival was defined by a prostate-specific antigen (PSA) level of 0.4 ng/mL or less after a nadir. The clinical, treatment, and dosimetric parameters evaluated for biochemical progression-free survival included BMI, patient age, clinical T stage, Gleason score, preimplant PSA level, risk group, percentage of positive biopsies, isotope, use of supplemental external beam radiotherapy, use of ADT, prostate volume, planning volume, percentage of target volume receiving 100%, 150%, and 200% of the prescribed dose, minimal percentage of dose covering 90% of the target volume, tobacco use, and the presence of hypertension and diabetes. For the entire group, the actuarial 8-year biochemical progression-free survival rate was 95.8%, 95.6%, 94.1%, and 100% for patients in BMI categories less than 25, 25.0 to 29.9, 30.0 to 34.9, and 35 or more kg/m2, respectively. In hormone-naive and hormone-manipulated patients free of biochemical progression, the median post-treatment PSA level was less than 0.1 ng/mL. When integrated across risk groups and ADT use, BMI had no statistically significant impact on biochemical progression-free survival. At last follow-up, 5 patients (0.7%) had died of metastatic prostate cancer. In multivariate Cox regression analysis, pretreatment PSA level, Gleason score, clinical stage, percentage of positive biopsies, ADT use, and tobacco status, but not BMI, were statistically significant predictors of 8-year biochemical progression-free survival. Prostate brachytherapy results in a high probability of 8-year biochemical progression-free survival for low, intermediate, and high-risk patients. When integrated across risk groups and hormonal status, BMI had no statistically significant influence on biochemical progression-free survival.

Permanent interstitial brachytherapy in younger patients with clinically organ-confined prostate cancer

Objectives To evaluate biochemical progression-free survival in hormone-naive men 62 years of age or younger with clinically organ-confined prostate cancer who underwent brachytherapy with or without supplemental external beam radiotherapy. Methods From April 1995 through December 2000, 119 hormone-naive patients 62 years of age or younger underwent permanent interstitial brachytherapy for clinical T1b-T2cNxM0 (2002 American Joint Committee on Cancer) prostate cancer. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. The median follow-up was 5.4 years. Biochemical progression-free survival was defined by either a prostate-specific antigen (PSA) level of 0.4 ng/mL or less after a nadir or by the American Society for Therapeutic Radiology and Oncology consensus definition. No patient was lost to follow-up. The clinical, treatment, and dosimetric parameters evaluated for biochemical progression-free survival included age, clinical T stage, Gleason score, pretreatment PSA level, risk group, percentage of positive biopsies, isotope, supplemental external beam radiotherapy, prostate volume, brachytherapy planning volume, percentage of the target volume receiving 100%, 150%, and 200% of the prescribed dose, minimal percentage of the prescribed dose covering 90% of the target volume, and tobacco status. Results For the entire group, the actuarial 7-year biochemical progression-free survival rate was 96.1% and 98.3% for a PSA cutpoint of 0.4 ng/mL or less and for the American Society for Therapeutic Radiology and Oncology consensus definition, respectively. Using a PSA biochemical control definition of 0.4 ng/mL or less, 93.1%, 100%, and 95.2% of the low-risk, intermediate-risk, and high-risk hormone-naive patients were free of biochemical progression. The median post-treatment PSA level for the biochemically disease-free group was less than 0.1 ng/mL. In multivariate analysis, only the pretreatment PSA level predicted the biochemical outcome. Conclusions Hormone-naive patients 62 years of age or younger have a high probability of 7-year biochemical progression-free survival after permanent interstitial brachytherapy with or without supplemental external beam radiotherapy.

Biochemical disease-free survival and toxicity associated with permanent prostate brachytherapy for men &lt; 60 years of age

4718 Background: To evaluate the biochemical disease-free survival (bDFS) and GI/GU toxicity for men 60 years of age or less who underwent transperineal ultrasound-guided I-125 permanent prostate brachytherapy (PPB). Methods: A total of 71 patients, age ≤ 60 underwent transperineal ultrasound guided PPB using I-125 for clinical stage T1c –T2a, Nx, M0 (2002 AJCC), Gleason score 6, adenocarcinoma of the prostate from November 1995 to December 2002. No patients received external beam radiation therapy. 18 patients (25%) received neoadjuvant hormonal manipulation with a median duration of 5 months (range, 2–10). The median patient age was 57 years (range, 42–60). 77% (55/71) reported erectile function sufficient for vaginal penetration prior to therapy. Patients were followed for PSA response/relapse, and GI/GU morbidity. Median follow-up was 34 months (range, 7 –81). Results: The actuarial bDFS rate was 93.0 % at 5 years. The median post-treatment prostate-specific antigen (PSA) nadir was 0.5 ng/mL. A total of 7% (5/71) developed acute urinary retention, and 3% (2/71) reported rectal bleeding in follow-up. One patient required a TURP as a complication for obstruction, and developed chronic incontinence thereafter. Chronic incontinence was not reported by any other patients. Of the patients potent prior to treatment, 65% (36/55) reported potency without the aid of medications, and 20% (11/55) with the assistance of medication, at the date of last follow-up. The remainder 15% (8/55) reported impotence, or no interest regaining erectile function. Conclusions: Early stage, good prognosis, prostate cancer patients ≤ 60 years of age have a high probability of bDFS following I-125 PPB. Risk of incontinence and rectal injury is low. Although potency is affected by therapy, the overall risk of erectile dysfunction is low (15%) when medical therapy is initiated. No significant financial relationships to disclose.

Biochemical outcome for hormone-naı̈ve intermediate-risk prostate cancer managed with permanent interstitial brachytherapy and supplemental external beam radiation

Purpose: To report the 6-year biochemical disease-free outcome for hormone-naı̈ve patients with intermediate-risk disease (Gleason score ≥7, prostate-specific antigen (PSA) ≥10 ng/ml, or clinical stage ≥T2b [1997 American Joint Committee on Cancer]) undergoing brachytherapy with supplemental external beam radiation (XRT). Methods and Materials: Seventy-seven consecutive hormone-naı̈ve intermediate-risk prostate cancer patients received supplemental XRT followed by a brachytherapy boost. No patient underwent pathologic lymph node staging. The median patient age was 69 years and the median follow-up was 52 months. Biochemical disease-free survival was defined by the American Society of Therapeutic Radiology and Oncology consensus definition. Clinical and treatment parameters evaluated included patient age, clinical stage, Gleason score, pretreatment PSA, and isotope. Results: The 6-year actuarial biochemical no-evidence-of-disease survival rate was 97.4%. None of the evaluated clinical or treatment parameters, except for a Gleason score ≥8, predicted for failure. The mean and median posttreatment PSA was 0.08 ± 0.19 ng/ml and <0.1 ng/ml, respectively. When stratified by isotope, the mean posttreatment PSA was not significantly different (0.07 ± 0.11 ng/ml for 103Pd vs. 0.14 ± 0.32 ng/ml for 125I; p = 0.397). Conclusions: Hormone-naı̈ve intermediate-risk prostate cancer patients undergoing brachytherapy with supplemental XRT have a high probability of 6-year biochemical disease-free survival. None of the evaluated clinical or treatment parameters, except Gleason score ≥8, predicted for treatment failure.

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

Purpose: To evaluate 5-year biochemical disease-free outcome for hormone naı̈ve 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 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. 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 naı̈ve 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.