Prostate-specific Antigen Failure Rates Research Articles

High-dose-rate brachytherapy as monotherapy for low- and intermediate-risk prostate cancer: long-term experience of Swedish single-center.

PurposeUntil now, most long-term results for brachytherapy only has been published for low-dose-rate (LDR) seeds. Due to radiobiology reasons, high-dose-rate (HDR) mono-brachytherapy is of growing interest. The aim of the study was to report long-term biochemical control rate and toxicities with HDR monotherapy.Material and methodsThis was a retrospective single-institution experience, including 229 men, clinically staged T1c-T2b, Gleason 3 + 3 (prostate specific antigen (PSA) ≤ 15), or Gleason 3 + 4 (PSA ≤ 10), consecutively treated between 2004 and 2012 with HDR brachytherapy alone, using three different fractionation schedules of 92-95 Gy (EQD(2), α/β = 3). Group 4F (n = 19) had a single implant of 9.5 Gy in four fractions over 2 days. Group 3F (n = 107) had three separate implants of 11 Gy over 4 weeks. Group 2F (n = 103) had two implants of 14 Gy over 2 weeks. No adjuvant hormonal therapy was allowed.ResultsFor 4F, 3F, and 2F study groups, median follow-up was 10.2, 7.1, and 6.1 years, respectively, and biochemical failure rate was 10.5%, 4.7%, and 14.6%, respectively. Early and late side effects were followed with common terminology criteria version 2.0 and patient-reported questionnaires. There were a temporary acute urethral toxicity increase, 1-2 grades over baseline lower urinary tract symptoms (LUTS), which usually recovered. About 1/3 of the patients had a remaining one grade over baseline LUTS. Severe grade 3-4 toxicity were only found in 3.5% of patients. No rectal toxicity was observed. Erectile dysfunction (ED) was depending on age and erectile function before treatment. In patients without ED before the treatment, we found a complete ED in 21% of men at the last follow-up.ConclusionsIn the present study, HDR mono-brachytherapy was found to be an effective treatment, with mild long-term side effects difficult to differentiate from aging effects. There were no significant differences in PSA regression, PSA failure rate, and toxicity between the different fraction schedules.

Effect of Long-Term Hormonal Therapy (vs Short-Term Hormonal Therapy): A Secondary Analysis of Intermediate-Risk Prostate Cancer Patients Treated on NRG Oncology RTOG 9202

NRG Oncology RTOG 9202 was a randomized trial testing long-term adjuvant androgen deprivation (LTAD) versus initial androgen deprivation only (STAD) with external beam radiation therapy (RT) in mostly high-risk and some intermediate-risk prostate cancer patients. RTOG 9408 found an overall survival (OS) advantage in patients with cT1b-T2b disease and prostate-specific antigen (PSA) <20ng/mL, with benefit observed mostly among intermediate-risk patients. It was still unknown whether intermediate-risk patients would experience an additional survival benefit with LTAD; thus, we performed a secondary analysis to explore whether LTAD had any incremental benefit beyond STAD among the intermediate-risk subset of RTOG 9202. The study endpoints were OS, disease-specific survival (DSS), and PSA failure (PSAF). An analysis was performed for all patients enrolled in RTOG 9202 defined as intermediate-risk (cT2 disease, PSA<10ng/mL, and Gleason score=7 or cT2 disease, PSA 10-20ng/mL, and Gleason score <7). This review yielded 133 patients: 74 (STAD) and 59 (LTAD). The Kaplan-Meier method was used to estimate OS; the cumulative incidence approach was used to estimate DSS and PSAF. A 2-sided test was used, with significance level defined to be .05. With over 11years of median follow-up, 39 STAD patients were alive and 33 LTAD patients were alive. There was no difference in OS (10-year estimates, 61% STAD vs 65% LTAD; P=.53), DSS (10-year DSS, 96% vs 97%; P=.72), or PSAF (10-year PSAF, 53% vs 55%; P=.99) between groups. LTAD did not confer a benefit in terms of OS, DSS, or PSAF rates in the intermediate-risk subset in this study. Whereas the subset was relatively small, treatment assignment was randomly applied, and a trend in favor of LTAD would have been of interest. Given the small number of disease-specific deaths observed and lack of benefit with respect to our endpoints, this secondary analysis does not suggest that exploration of longer hormonal therapy is worth testing in the intermediate-risk prostate cancer subset.

Gleason Score ≤ 6 Prostate Cancer at Radical Prostatectomy: Does a High-Risk Setting Truly Exist? A Recursive Partitioning Analysis

BackgroundThe purpose of this study was to determine whether a “high-risk” subpopulation of low-grade (Gleason score ≤6) prostate cancer defined by lower prostate-specific antigen (PSA) relapse-free survival (bRFS) might be identified within a large population of men who underwent radical prostatectomy (RP) alone, with mature follow-up. Patients and MethodsPatients were retrospectively identified for inclusion by cT1-2 prostate cancer managed with RP alone. Exclusion criteria were: Gleason score ≥7 at RP, any pre- or post-RP radiotherapy or hormone therapy, or PSA follow-up <12 months. The Kaplan–Meier method was used for survival estimates; recursive partitioning by conditional inference analysis was applied to identify variables associated with bRFS. ResultsFrom 2002 through 2010, 284 eligible patients were identified. Median age was 60 years (range, 44-76 years), 233 (82%) were cT1c, and median PSA was 5.3 ng/dL (92% ≤10). The median biopsy to RP interval was 50 days (range, 11-410, with 97% <180 days). Eighty patients (28%) had positive margin (M+). At a median follow-up of 92.6 months (range, 16.9-160.9, with 45% followed ≥ 8 years), 32 patients (11%) had PSA failure, with an estimated 8-year bRFS rate of 89%. In univariate analysis, M+, extraprostatic extension, detectable initial post-RP PSA, and longer biopsy to RP interval were significantly associated with lower bRFS. M+ and longer biopsy to RP interval remained significant in multivariable analysis. Recursive partitioning analysis identified M+ as the only stratification factor, with 8-year bRFS estimates of 74% versus 95% for M+ versus margin-negative. ConclusionGleason score ≤6 prostate cancer managed using RP alone is associated with high rates of bRFS; however, margin positivity predicts early PSA failure rates in >20% of patients.

Long-term follow-up of a large active surveillance cohort of patients with prostate cancer.

Active surveillance is increasingly accepted as a treatment option for favorable-risk prostate cancer. Long-term follow-up has been lacking. In this study, we report the long-term outcome of a large active surveillance protocol in men with favorable-risk prostate cancer. In a prospective single-arm cohort study carried out at a single academic health sciences center, 993 men with favorable- or intermediate-risk prostate cancer were managed with an initial expectant approach. Intervention was offered for a prostate-specific antigen (PSA) doubling time of less than 3 years, Gleason score progression, or unequivocal clinical progression. Main outcome measures were overall and disease-specific survival, rate of treatment, and PSA failure rate in the treated patients. Among the 819 survivors, the median follow-up time from the first biopsy is 6.4 years (range, 0.2 to 19.8 years). One hundred forty-nine (15%) of 993 patients died, and 844 patients are alive (censored rate, 85.0%). There were 15 deaths (1.5%) from prostate cancer. The 10- and 15-year actuarial cause-specific survival rates were 98.1% and 94.3%, respectively. An additional 13 patients (1.3%) developed metastatic disease and are alive with confirmed metastases (n = 9) or have died of other causes (n = 4). At 5, 10, and 15 years, 75.7%, 63.5%, and 55.0% of patients remained untreated and on surveillance. The cumulative hazard ratio for nonprostate-to-prostate cancer mortality was 9.2:1. Active surveillance for favorable-risk prostate cancer is feasible and seems safe in the 15-year time frame. In our cohort, 2.8% of patients have developed metastatic disease, and 1.5% have died of prostate cancer. This mortality rate is consistent with expected mortality in favorable-risk patients managed with initial definitive intervention.

Active Surveillance: The Canadian Experience With an "Inclusive Approach"

Active surveillance has evolved to become a standard of care for favorable-risk prostate cancer. This is a summary of the rationale, method, and results of active surveillance beginning in 1995 with the first prospective trial of this approach. This was a prospective, single-arm cohort study. Patients were managed with an initial expectant approach. Definitive intervention was offered to those patients with a prostate-specific antigen (PSA) doubling time of less than 3 years, Gleason score progression (to 4+3 or greater), or unequivocal clinical progression. Survival analysis and Cox proportional hazard model were applied to the data. Since November 1995, 450 patients have been managed with active surveillance. The cohort included men under 70 with favorable-risk disease and men of age more than 70 with favorable- or intermediate-risk cancer (Gleason score 3+4 or PSA 10-15). Median follow-up is 6.8 years (range 1-16 years). Overall survival is 78.6%. Ten-year prostate cancer actuarial survival is 97.2%. Five of 450 patients (1.1%) have died of prostate cancer. Thirty percent of patients have been reclassified as higher-risk patients and offered definitive therapy. The commonest indication for treatment was a PSA doubling time less than 3 years (48%) or Gleason upgrading (26%). Of 117 patients treated radically, the PSA failure rate was 50%. This represents 13% of the total cohort. Most PSA failures occurred early; at 2 years, 44% of the treated patients had PSA failure. The hazard ratio for non-prostate cancer mortality to prostate cancer mortality was 18.6 at 10 years. In conclusion, we observed a very low rate of prostate cancer mortality in an intermediate time frame. Among the one-third of patients who were reclassified as higher risk and retreated, PSA failure was relatively common. However, other-cause mortality accounted for almost all of the deaths. Further studies are warranted to improve the identification of patients who harbor more aggressive disease in spite of favorable clinical parameters at diagnosis [reproduced from Klotz (1) with permission from Wolters Kluwer Health].

Active surveillance

Active surveillance has evolved to become a standard of care for favorable-risk prostate cancer. This article is a summary of the rationale, method, and results of active surveillance beginning in 1995 with the first prospective trial of this approach. This was a prospective, single arm cohort study. Patients were managed with an initial expectant approach. Definitive intervention was offered to those patients with a prostate specific antigen (PSA) doubling time of less than 3 years, Gleason score progression (to 4 + 3 or greater), or unequivocal clinical progression. Since November 1995, 450 patients have been managed with active surveillance. Median follow-up is 6.8 years (range 1-16 years). Overall survival is 78.6%. Ten-year prostate cancer actuarial survival is 97.2%. Five of 450 patients (1.1%) have died of prostate cancer. Thirty percent of patients have been reclassified as higher risk and offered definitive therapy. The commonest indication for treatment was a PSA doubling time less than 3 years (48%) or Gleason upgrading (26%). Of 117 patients treated radically, the PSA failure rate was 50%. This represents 13% of the total cohort. Most PSA failures occurred early; at 2 years, 44% of the treated patients had PSA failure. The hazard ratio for nonprostate cancer to prostate cancer mortality was 18.6 at 10 years. We observed a very low rate of prostate cancer mortality in an intermediate time frame. Among the one-third of patients who were reclassified as higher risk and retreated, PSA failure was relatively common. However, other cause mortality accounted for almost all of the deaths. Further studies are warranted to improve the identification of patients who harbor more aggressive disease in spite of favorable clinical parameters at diagnosis.

Does the outcome of prostate cancer patients with large prostates differ from small prostate size in permanent seed, low dose-rate brachytherapy?

Brachytherapy has good results in the treatment of early prostate cancer (PC). The procedure is challenging in large prostates, and the optimal prostate volume for brachytherapy was previously defined as ≤40 ml. This study analysed the outcome of PC patients with small (group A) and large (group B) prostate volume in prospective data. The material consisted of 535 consecutive patients treated with brachytherapy in Kuopio University Hospital. The mean follow-up time was nearly 6 years. Prostate-specific antigen (PSA) failure was defined as PSA rising ≥2.0 μg/l above nadir. A PSA bounce was defined as a rise in PSA of ≥0.2 μg/l. The causes of death were recorded. A bounce was recorded more frequently in group A (30%) than in group B (18%) (p = 0.006). A bounce correlated with young age predicted a favourable outcome in both groups. PSA failure rate was similar in both groups: 13% and 12% in groups A and B, respectively. Post-treatment PSA ≤0.5 μg/l was the only independent prognostic factor associated with PSA failure in both groups (p < 0.0001, both groups). PC survival was 98.4% in both groups. Overall survival was 91% and 94% in groups A and B, respectively (p = not significant). There were no differences between the PC patients with small and large prostate volumes treated with brachytherapy with respect to PSA failure rate, PC survival or overall survival. All patients, independent of prostate size, are potential candidates for brachytherapy.

Robotic Radical Prostatectomy at a Teaching Community Hospital: Outcomes and Safety

This study describes the early experience of robotic prostatectomy exclusively at a teaching community hospital. This is a retrospective report of 153 consecutive patients on whom 4 physicians were the operating surgeon. The average hospital stay was 1.5 days, the mean operative time was 175 minutes, and the estimated operative blood loss was <300mL. The perioperative complication rate was 7.8% (12/153). The prostate-specific antigen failure rate was 2% (2/114). Urinary continence was maintained in 98% of patients 9 months after surgery. Postoperative Gleason scores differed significantly from preoperative biopsy results (P<0.001). Pathological records reported positive margins in 35% (54/153) of specimens. T3 tumors had positive margins more than twice as often as T2 tumors (P<0.002). Surgeon experience correlated with shorter operative times (P=0.001), but not with positive margins. Increasing body mass index was associated with increased operating time (P<0.001). Robotic prostatectomy appears to be a safe and successful option for prostate cancer treatment in a teaching community hospital.

Analysis of Initial Baseline Clinical Parameters and Treatment Strategy Associated with Medication Failure in the Treatment of Benign Prostatic Hyperplasia in Korea

PurposeTo analyze the baseline clinical factors and medication treatment strategy used in cases with medication treatment failure of benign prostatic hyperplasia (BPH).MethodsFrom January 2006 to December 2009, 677 BPH patients with at least 3 months of treatment with medication were enrolled. We analyzed clinical factors by medication failure (n=161) versus maintenance (n=516), by prostate size (less than 30 g, n=231; 30 to 50 g, n=244; greater than 50 g, n=202), and by prostate-specific antigen (PSA) levels (less than 1.4 ng/mL, n=324; more than 1.4 ng/mL, n=353).ResultsAge, combination medication rate, PSA, and prostate volume were statistically different between the medication treatment failure and maintenance groups. By prostate size, the PSA and medication failure rates were relatively higher and the medication period was shorter in patients with a prostate size of more than 30 g. The combination medication rate was higher in patients with a prostate size of more than 50 g. The medication failure rate and prostate volume were higher in patients with a PSA level of more than 1.4 ng/mL. However, the combination treatment rate was not significantly different in patients with a PSA level lower than 1.4 ng/mL. Suggestive cutoffs for combination medication are a prostate volume of 34 g and PSA level of 1.9 ng/mL.ConclusionsThe clinical factors associated with medication failure were age, treatment type, and prostate volume. Combination therapy should be considered more in Korea in patients with a PSA level higher than 1.4 ng/mL and a prostate volume of between 30 and 50 g to prevent medication failure.

Long-term prostate-specific antigen (PSA) control in prostate cancer (PCa) patients switched from leuprolide to degarelix or receiving continuous degarelix treatment.

4673 Background: Gonadotropin releasing-hormone (GnRH) blockers are a new type of fast-acting hormonal therapy for prostate cancer, which are devoid of agonist-associated surge/microsurges. Degarelix (approved dose 240/80 mg), a new GnRH blocker, was recently compared with leuprolide over 1-year of prostate cancer treatment in the CS21 trial. Here we report long-term PSA and musculoskeletal adverse event (AE) data from the extension study (CS21A). Methods: Patients with histologically confirmed prostate cancer were randomized to degarelix [starting dose 240 mg, and monthly maintenance doses of 80 mg (n=207) or 160 mg (n=202)], or leuprolide 7.5 mg/month (n=201). After 1 year, patients receiving leuprolide were re-randomised to degarelix 240/80 mg or 240/160 mg treatment. PSA progression-free survival (PFS) was defined as time to first of PSA failure (i.e. two consecutive increases in PSA of 50% and ≥5 ng/mL compared with nadir) or death. Data were also assessed by baseline PSA level. Results: After 1 year of treatment, the PSA failure rate decreased in patients switched from leuprolide to degarelix and the Kaplan-Meier curves for PSA PFS became superimposed. An additional analysis (October 2009) indicated a significant PSA PFS hazard change from 0.20 events/year in the first year to 0.09 events/year following the switch for leuprolide patients (p=0.0059); the corresponding hazards for degarelix at these time points were 0.11 and 0.14 (p=0.45). The same pattern occurred in patients with baseline PSA levels >20 ng/mL (leuprolide year 1: 0.38 vs 0.20 post switch [p=0.0367]; degarelix: 0.23 vs 0.23 [p=0.94]). Up to 1 year, musculoskeletal and connective tissue AEs occurred in 17% (degarelix) vs 26% (leuprolide; p<0.05) of patients. Beyond 1 year, these AEs were similar in the two groups (16% vs 18% [p=0.75]). Conclusions: These data suggest that patients with hormone-sensitive PCa receiving leuprolide experience improved PSA control after switching to degarelix. Patients receiving continuous degarelix have fewer musculoskeletal AEs. Further studies are required to confirm these findings. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ferring Pharmaceuticals Ferring Pharmaceuticals Ferring Pharmaceuticals Ferring Pharmaceuticals

Clinical Results of Long-Term Follow-Up of a Large, Active Surveillance Cohort With Localized Prostate Cancer

PURPOSE We assessed the outcome of a watchful-waiting protocol with selective delayed intervention by using clinical prostate-specific antigen (PSA), or histologic progression as treatment indications for clinically localized prostate cancer. PATIENTS AND METHODS This was a prospective, single-arm, cohort study. Patients were managed with an initial expectant approach. Definitive intervention was offered to those patients with a PSA doubling time of less than 3 years, Gleason score progression (to 4 + 3 or greater), or unequivocal clinical progression. Survival analysis and Cox proportional hazard model were applied to the data. Results A total of 450 patients have been observed with active surveillance. Median follow-up was 6.8 years (range, 1 to 13 years). Overall survival was 78.6%. The 10-year prostate cancer actuarial survival was 97.2%. Overall, 30% of patients have been reclassified as higher risk and have been offered definitive therapy. Of 117 patients treated radically, the PSA failure rate was 50%, which was 13% of the total cohort. PSA doubling time of 3 years or less was associated with an 8.5-times higher risk of biochemical failure after definitive treatment compared with a doubling time of more than 3 years (P < .0001). The hazard ratio for nonprostate cancer to prostate cancer mortality was 18.6 at 10 years. CONCLUSION We observed a low rate of prostate cancer mortality. Among the patients who were reclassified as higher risk and who were treated, PSA failure was relatively common. Other-cause mortality accounted for almost all of the deaths. Additional studies are warranted to improve the identification of patients who harbor more aggressive disease despite favorable clinical parameters at diagnosis.

Prognostic Significance of 5-Year PSA Value for Predicting Prostate Cancer Recurrence After Brachytherapy Alone and Combined With Hormonal Therapy and/or External Beam Radiotherapy

To analyze the prognosis and outcomes of patients who remain free of biochemical failure during the first 5 years after treatment. Between 1991 and 2002, 742 patients with prostate cancer were treated with brachytherapy alone (n = 306), brachytherapy and hormonal therapy (n = 212), or combined implantation and external beam radiotherapy (with or without hormonal therapy; n = 224). These patients were free of biochemical failure (American Society for Therapeutic Radiology and Oncology [ASTRO] definition) during the first 5 post-treatment years and had a documented 5-year prostate-specific antigen (PSA) value. The median follow-up was 6.93 years. The actuarial 10-year freedom from PSA failure rate was 97% using the ASTRO definition and 95% using the Phoenix definition. The median 5-year PSA level was 0.03 ng/mL (range, 0-3.6). The 5-year PSA value was <or=0.01 in 47.7%, >0.01-0.10 in 31.1%, >0.10-0.2 in 10.2%, >0.2-0.5 in 7.82%, and >0.5 in 3.10%. The 5-year PSA value had prognostic significance, with a PSA value of <or=0.2 ng/mL (n = 661) corresponding to a 10-year freedom from PSA failure rate of 99% with the ASTRO definition and 98% with the Phoenix definition vs. 86% (ASTRO definition) and 81% (Phoenix definition) for a PSA value >or=0.2 ng/mL (n = 81; p < .0001). The treatment regimen had no effect on biochemical failure. None of the 742 patients in this study developed metastatic disease or died of prostate cancer. The results of this study have shown that the prognosis for patients treated with brachytherapy and who remain biochemically free of disease for >or=5 years is excellent and none developed metastatic disease during the first 10 years after treatment. The 5-year PSA value is prognostic, and patients with a PSA value <0.2 ng/mL are unlikely to develop subsequent biochemical relapse.

Body mass index and prostate-specific antigen failure following brachytherapy for localized prostate cancer: Efstathiou JA, Skowronski RY, Coen JJ, Grocela JA, Hirsch AE, Zietman AL, Mark A. Ritter, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA.

Purpose Increasing body mass index (BMI) is associated with prostate-specific antigen (PSA) failure after radical prostatectomy and external beam radiation therapy (EBRT). We investigated whether BMI is associated with PSA failure in men treated with brachytherapy for clinically localized prostate cancer. Patients and Methods Retrospective analyses were conducted on 374 patients undergoing brachytherapy for stage T1c-T2cNXM0 prostate cancer from 1996 to 2001. Forty-nine patients (13%) received supplemental EBRT and 131 (35%) received androgen deprivation therapy (ADT). Height and weight data were available for 353 (94%). Cox regression analyses were performed to evaluate the relationship between BMI and PSA failure (nadir + 2 ng/ml definition). Covariates included age, race, preimplantation PSA, Gleason score, T category, percent of prescription dose to 90% of the prostate, use of supplemental EBRT, and ADT. Results Median age, PSA, and BMI were 66 years (range, 42–80 years), 5.7 ng/mL (range, 0.4–22.6 ng/mL), and 27.1 kg/m 2 (range, 18.2–53.6 kg/m 2 , respectively. After a median follow-up of 6.0 years (range, 3.0–10.2 years), there were 76 PSA recurrences. The BMI was not associated with PSA failure. Six-year PSA failure rates were 30.2% for men with BMI less than 25 kg/m 2 , 19.5% for BMI of 25 or greater to less than 30 kg/m 2 , and 14.4% for BMI of 30 kg/m 2 or greater ( P = 0.19). Results were similar when BMI was analyzed as a continuous variable, using alternative definitions of PSA failure, and excluding patients treated with EBRT and/or ADT. In multivariate analyses, only baseline PSA was significantly associated with shorter time to PSA failure (adjusted hazard ratio, 1.12; 95% confidence interval, 1.05–1.20; P = 0.0006). Conclusions Unlike after surgery or EBRT, BMI is not associated with PSA failure in men treated with brachytherapy for prostate cancer. This raises the possibility that brachytherapy may be a preferred treatment strategy in obese patients.

Body Mass Index and Prostate-Specific Antigen Failure Following Brachytherapy for Localized Prostate Cancer

Increasing body mass index (BMI) is associated with prostate-specific antigen (PSA) failure after radical prostatectomy and external beam radiation therapy (EBRT). We investigated whether BMI is associated with PSA failure in men treated with brachytherapy for clinically localized prostate cancer. Retrospective analyses were conducted on 374 patients undergoing brachytherapy for stage T1c-T2cNXM0 prostate cancer from 1996-2001. Forty-nine patients (13%) received supplemental EBRT and 131 (35%) received androgen deprivation therapy (ADT). Height and weight data were available for 353 (94%). Cox regression analyses were performed to evaluate the relationship between BMI and PSA failure (nadir + 2 ng/ml definition). Covariates included age, race, preimplantation PSA, Gleason score, T category, percent of prescription dose to 90% of the prostate, use of supplemental EBRT, and ADT. Median age, PSA, and BMI were 66 years (range, 42-80 years), 5.7 ng/ml (range, 0.4-22.6 ng/ml), and 27.1 kg/m(2) (range, 18.2-53.6 kg/m(2)), respectively. After a median follow-up of 6.0 years (range, 3.0-10.2 years), there were 76 PSA recurrences. The BMI was not associated with PSA failure. Six-year PSA failure rates were 30.2% for men with BMI less than 25 kg/m(2), 19.5% for BMI of 25 or greater to less than 30 kg/m(2), and 14.4% for BMI of 30 kg/m(2) or greater (p = 0.19). Results were similar when BMI was analyzed as a continuous variable, using alternative definitions of PSA failure, and excluding patients treated with EBRT and/or ADT. In multivariate analyses, only baseline PSA was significantly associated with shorter time to PSA failure (adjusted hazard ratio, 1.12; 95% confidence interval, 1.05-1.20; p = 0.0006). Unlike after surgery or EBRT, BMI is not associated with PSA failure in men treated with brachytherapy for prostate cancer. This raises the possibility that brachytherapy may be a preferred treatment strategy in obese patients.

Body Mass Index and PSA Failure Following Brachytherapy for Localized Prostate Cancer

Greater body mass index (BMI) is associated with shorter time to prostate-specific antigen (PSA) failure following radical prostatectomy and external beam radiation therapy (EBRT) with or without androgen deprivation therapy (ADT). We investigated whether BMI is associated with time to PSA failure in a cohort of men treated with permanent prostate brachytherapy for clinically localized prostate cancer. A retrospective analysis was conducted on 374 consecutive patients who underwent brachytherapy with or without supplemental EBRT and/or ADT for clinical stage T1c-T2c NX M0 prostate cancer between August 1996 and December 2001 and who had a minimum follow-up of 3 years. Forty-nine (13%) of these patients received supplemental EBRT and 131 (35%) received ADT, while 207 (55.4%) were treated with brachytherapy only. Height and weight data were available at baseline for 353 (94%) of the men. Cox regression analyses were performed to evaluate the relationship between BMI and time to PSA failure (nadir + 2 ng/ml definition). Covariates included age, race, pre-implant PSA level, Gleason score, T-category, use of supplemental EBRT, and use of ADT. Median age, PSA, and BMI at baseline were 66 (range 42–80) years, 5.7 (range 0.4–22.6) ng/ml, and 27.1 (range 18.2–53.6) kg/m2, respectively. After a median follow-up of 6.0 (range 3.0–10.2) years, there were a total of 76 PSA failures. BMI was not associated with PSA failure. At 6-years, the PSA failure rate was 30.2% for men with BMI < 25 kg/m2, 19.5% for men with BMI ≥25–<30, and 14.4% for men with BMI ≥30 (p = 0.19). Results were similar when BMI was analyzed as a continuous variable, when using alternative definitions of PSA failure, and when excluding patients treated with EBRT and/or ADT. In multivariate analyses, only baseline PSA was significantly associated with shorter time to PSA failure [adjusted HR 1.12, 95% CI 1.05–1.20, p = 0.0006] (Table). Unlike following surgery or EBRT, a greater baseline BMI is not associated with higher PSA failure rates in men treated with brachytherapy for clinically localized prostate cancer. This raises the possibility that brachytherapy may be a preferred treatment strategy for obese patients.TableMultivariate Analysis of PSA Failure using Nadir +2 Definition (n = 350)CovariateAdjusted HR [95% CI]p-valueBMI (kg/m2) <25—— ≥25–<300.76 [0.45–1.29]0.31 ≥300.56 [0.29–1.10]0.091Baseline PSA (ng/ml), continuous1.12 [1.05–1.20]0.0006Gleason score ≤6—— 71.64 [0.91–2.96]0.099 8–100.94 [0.22–4.00]0.93Tumor category T1—— T20.81 [0.45–1.43]0.46EBRT No—— Yes1.12 [0.56–2.23]0.75ADT No—— Yes1.11 [0.68–1.83]0.68Race Black—— Other0.49 [0.22–1.07]0.073 Open table in a new tab

Prostate Cancers Scored as Gleason 6 on Prostate Biopsy are Frequently Gleason 7 Tumors at Radical Prostatectomy: Implication on Outcome

Differentiation between Gleason score 6 and 7 in prostate biopsy is important for treatment decision making. Nevertheless, under grading errors compared with the actual pathological grade at radical prostatectomy are common. We compared the characteristics and outcomes of tumors that were scored 6 on prostate biopsy but were 7 on subsequent radical prostatectomy pathological evaluation to those in tumors with a consistent rating of Gleason score 6 or 7 at biopsy and surgery. We performed a retrospective database analysis from our referral center (1989 to 2004). We compared pre-prostatectomy characteristics, radical prostatectomy pathological features and the post-radical prostatectomy prostate specific antigen failure rate, defined as any 2 consecutive detectable prostate specific antigen measurements, in 3 subgroups of patients, including 156 with matched Gleason score 6 in the prostate biopsy and radical prostatectomy, 205 with upgraded Gleason score 6/7, that is prostate biopsy Gleason score 6 and radical prostatectomy Gleason score 7, and 412 with matched Gleason score 7 in the prostate biopsy and radical prostatectomy. Radical prostatectomy Gleason score matched the prostate biopsy score in 38.2% of biopsy Gleason score 6 and 81.4% of biopsy Gleason score 7 cases. Higher prostate specific antigen was associated and an increased percent of cancer in the prostate biopsy was predictive of discordance between the prostate biopsy and radical prostatectomy Gleason scores (p <0.001). Margin (p = 0.0075) or seminal vesicle involvement (p = 0.0002), cancer volume (p <0.001) and the prostate specific antigen failures rate (p = 0.014) were significantly higher in under graded Gleason score 7 cancer compared to those in matched Gleason score 6 cases. However, they were comparable to those with a matched Gleason score 7 tumor grade (p = 0.66). Almost half of tumors graded Gleason score 6 at biopsy are Gleason score 7 at surgery. Upgraded Gleason score 6 to 7 tumors have outcomes similar to those of genuine Gleason score 7 cancer. For prostate biopsy Gleason score 6 tumors clinicians should consider the overall likelihood of tumor upgrading as well as specific patient characteristics, such as prostate specific antigen and the percent of tumor in the prostate biopsy, when contemplating treatments that are optimized for low grade tumors, including watchful waiting or brachytherapy.

The Effect of Age on Prostate Implantation Results

The current study was undertaken to determine the effect of young age (60 years or younger) on the 5-year biochemical disease-free survival rate following ultrasound-guided transperineal prostate implantation. The radiation therapy charts of 330 patients who underwent ultrasound-guided transperineal prostate implantation who were treated from 1992 through 2004 were retrospectively reviewed. Follow-up ranged from 12 to 120 months, with a mean of 48 months. A total of 63 patients were 60 years of age or younger, and 267 patients were over 60 years of age. Prostate-specific antigen (PSA) recurrence was defined as three successive increases following ultrasound-guided transperineal prostate implantation. Biochemical disease-free survival was determined using the life-table method. There were no statistically significant differences in the 5-year biochemical disease-free survival rates for the younger versus the older group. On univariate analysis, age was not a statistically significant factor in predicting PSA failure. Univariate analysis revealed that Gleason score, PSA at diagnosis, and clinical T stage were significant in predicting for PSA failure. Patients with Gleason score<7, PSA<10, and clinical stage T1c disease had statistically significant lower PSA failure rates than patients with Gleason score>or=7, PSA>or=10, and clinical stage T2 disease, respectively. Patients who are 60 years of age or younger who are treated with ultrasound-guided transperineal prostate implantation can expect 5-year biochemical disease-free survival rates similar to those of older patients treated with ultrasound-guided transperineal prostate implantation therapy.

Combined modality treatment in the management of high-risk prostate cancer

Purpose The efficacy of a multimodality protocol using neoadjuvant and concomitant hormonal therapy, brachytherapy, and three-dimensional conformal external beam radiotherapy (RT) in high-risk prostate cancer was evaluated using biochemical outcomes and posttreatment biopsy results. Methods and materials Between February 1994 and November 1999, 132 high-risk patients were treated with combined hormonal therapy (9 months), permanent radioactive seed brachytherapy, and external beam RT, with follow-up ranging from 36 to 88 months (median, 50 months). The eligibility criteria were any of the following: Gleason score 8–10, initial prostate-specific antigen (PSA) level >20 ng/mL, clinical Stage T2c-T3, or positive seminal vesicle biopsy, or two or more of the following: Gleason score 7, PSA level >10–20 ng/mL, or Stage T2b. Twenty percent of patients had a positive seminal vesicle biopsy before therapy. Negative laparoscopic pelvic lymph node dissections were performed in 44% of patients. Results The actuarial overall freedom from PSA failure rate was 86% at 5 years. The freedom from PSA failure rate at 5 years was 97% for those with a Gleason score of ≤6 (35 of 36), 85% for a Gleason score of 7 (50 of 59), and 76% for a Gleason score of 8–10 (28 of 37; p = 0.03). A trend was noted toward worse outcomes in seminal vesicle biopsy-positive patients, with a 5-year freedom from PSA failure rate of 74% vs. 89% for all other patients ( p = 0.06). Posttreatment prostate biopsies were performed in 47 patients and were negative in 96% at the first biopsy and 100% at the last biopsy. Conclusion Trimodality therapy with androgen suppression, brachytherapy, and external beam RT for high-risk prostate cancer results in excellent biochemical and pathologically confirmed local control.

Invasion of seminal vesicles by adenocarcinoma of the prostate: PSA outcome determined by preoperative and postoperative factors

Objectives To determine which preoperative and postoperative factors were predictive of the time to prostate-specific antigen (PSA) failure after radical retropubic prostatectomy (RRP) for patients with seminal vesicle invasion (SVI). SVI by prostate cancer is associated with high PSA failure rates after RRP and subsequent distant metastases. Methods Between 1988 and 2002, 1697 patients with prostate cancer underwent RRP at Brigham and Women's Hospital, of whom 103 (6%) had SVI. Cox regression multivariable analysis was used to determine whether the preoperative PSA level, prostatectomy Gleason score, margin status, or presence of extraprostatic extension was predictive of the time to postoperative PSA failure. Estimates of PSA outcome were made using the actuarial method of Kaplan and Meier for patients who had none, all, or at least one of the factors that predicted for the time to postoperative PSA failure. Results The statistically significant categorical predictors of the time to PSA failure after RRP in patients with SVI included prostatectomy Gleason score of 4+3 or greater ( P = 0.009), preoperative PSA level greater than 20 ng/dL when evaluated as a categorical or as a continuous variable ( P = 0.002 and P = 0.001, respectively), and margin positivity ( P = 0.075) which was of borderline significance. The 3-year estimate of PSA control was 52% to 100%, 28%, and 0% for patients with negative margins, preoperative PSA less than 20 ng/dL, and prostatectomy Gleason score of 3+4 or less versus having one to two or all three predictors of the time to postoperative PSA failure. Conclusions The PSA outcome after RRP for patients with SVI varies depending on the preoperative PSA level, prostatectomy Gleason score, and margin status.

Should a Positive Surgical Margin Following Radical Prostatectomy be Pathological Stage T2 or T3? Results From the SEARCH Database

The finding of a positive surgical margin associated with extracapsular extension at radical prostatectomy is a poor prognostic factor. However, whether a positive surgical margin with no documented extracapsular extension portends a similarly poor prognosis is unclear. We examined the significance of the pathological features of positive surgical margin and extracapsular extension for predicting biochemical failure following radical prostatectomy. We examined data on 1,621 men from the SEARCH Database of patients treated with radical prostatectomy without lymph node metastasis. Patients were separated into 5 groups based on the pathological findings of positive surgical margin, extracapsular extension, and/or seminal vesicle invasion. Preoperative clinical variables were compared across the groups and the groups were compared for time to biochemical recurrence using Cox proportional hazards analysis. Men with seminal vesicle invasion had the highest prostate specific antigen (PSA) recurrence rates, while men with a negative surgical margin and no extracapsular extension had the lowest PSA recurrence rates. There were no differences in PSA failure rates between men with a positive surgical margin and no extracapsular extension versus men with a negative surgical margin and extracapsular extension versus men with extracapsular extension and a positive surgical margin. In this subset of patients with a positive surgical margin and/or extracapsular extension but no seminal vesicle invasion only serum PSA was a significant independent predictor of biochemical recurrence. Men with a positive surgical margin but no extracapsular extension had PSA recurrence rates similar to those in men with extracapsular extension with or without positive margins. Men with extracapsular extension had similar biochemical recurrence rates whether the surgical margin was positive or negative. If confirmed at other institutions, consideration should be given to modifying the current TNM staging system to reflect these findings.