Association of percent positive prostate biopsies and perineural invasion with biochemical outcome after external beam radiotherapy for localized prostate cancer

PURPOSE: Few studies have evaluated the significance of the percentage of positive biopsies (PPB) and perineural invasion (PNI) for patients treated with external beam radiotherapy (EBRT) for localized prostate cancer. Our goal was to investigate the value of these factors in predicting biochemical control (bNED) after EBRT. METHODS AND MATERIALS: The study cohort consisted of 331 patients who received EBRT between 1993 and 1999 for clinically localized prostate cancer. The median follow-up was 4.4 years (range, 3 months to 9.6 years). The distribution by clinical T stage was as follows: T1 in 55 (17%), T2a in 94 (28%), T2b in 76 (23%), T2c in 74 (22%), T3a in 27 (8%), and T3b in 5 (2%). The pretreatment prostate-specific antigen (iPSA) level was < or =10 ng/mL in 224 patients, 10.1-20 ng/mL in 72 patients, and >20 ng/mL in 35 patients. The biopsy Gleason score was < or =6 in 216 patients and > or =7 in 115 patients. On the basis of the pathology report, the PPB was calculated for 239 patients and was < or =33% in 109, 34-66% in 72, and > or =67% in 58 patients. PNI was present in 30 patients. The median dose of EBRT was 68.4 Gy (range, 64-71 Gy). Patients were categorized into three risk groups: 142 patients were low risk (T1-T2, iPSA < or =10 ng/mL, and Gleason score < or =6), 137 were intermediate risk (increase in the value of one of the risk factors); and 52 patients were high risk (increase in value of two or more of the risk factors). Biochemical failure was defined as three consecutive rises in the PSA level. RESULTS: The 5-year bNED rate for the entire cohort was 62%. The 5-year bNED rate for the low-, intermediate, and high-risk group was 79%, 51%, and 47%, respectively (p <0.0001). On univariate analysis (log-rank test), clinical stage (p = 0.0073), grade (p <0.0001), iPSA (p = 0.0043), risk group (p <0.0001), PPB (p = 0.0193), and presence of PNI (p = 0.0137) correlated with bNED. For T1-T2a, T2b-T2c, and T3 patients, the 5-year bNED rate was 71%, 59%, and 40%, respectively. The 5-year bNED rate was 68% for those with an iPSA level of < or =10 ng/mL and 49% for those with an iPSA level of >10 ng/mL. For patients with PPB < or =33%, 34-66%, and > or =67%, the 5-year bNED rate was 75%, 67%, and 51%, respectively. Within the intermediate-risk group, the PPB was significantly associated with the bNED rate: 67%, 52%, and 30% for those with PPB < or =33%, 34-66%, and > or =67%, respectively (p = 0.0046). This association was not seen in the low- or high-risk group. The 5-year bNED rate was 64% for patients without PNI and 48% for those with PNI. On multivariate analysis (Cox proportional hazards model), the statistically significant predictive factors for bNED were risk group (p = 0.0032) and PPB (p = 0.044). Using the chi-square test, statistically significant associations between T stage, PSA level, Gleason score, and risk group with PPB were found; PNI was significantly associated with T stage and PSA level only. CONCLUSION: Our results showed that PPB and PNI have a statistically significant impact on the bNED rate in patients treated with conventional dose of EBRT (< or =71 Gy). Within the intermediate-risk group, the PPB was predictive of bNED, suggesting that patients with < or =33% PPB had a statistically significant better treatment outcome compared with those with a greater PPB. PNI was not significant for bNED in multivariate analysis. The effects of these two prognostic factors in patients who have been treated with higher doses of RT (> or =75.6 Gy) should be studied.     

The clinical utility of the percent of positive prostate biopsies in predicting biochemical outcome following external-beam radiation therapy for patients with clinically localized prostate cancer

PURPOSE: An investigation was performed of the clinical utility of the percent of positive prostate biopsies in predicting prostate-specific antigen (PSA) outcome following external-beam radiation therapy (RT) for men with PSA-detected or clinically palpable prostate cancer. METHODS AND MATERIALS: A Cox regression multivariable analysis was used to determine whether the percent of positive prostate biopsies provided clinically relevant information about PSA outcome following external beam RT in 473 men while accounting for the previously established risk groups based on the pretreatment PSA level, biopsy Gleason score, and the 1992 American Joint Commission on Cancer (AJCC) clinical T stage. RESULTS: Controlling for the known prognostic factors, the percent of positive prostate biopsies added clinically significant information (p = 0.02) regarding time to PSA failure following RT. Specifically, 76% of the patients in the intermediate risk group (1992 AJCC T(2b) or biopsy Gleason 7 or PSA > 10 ng/mL and < or = 20 ng/mL) could be classified into either an 30% or 85% 5-year PSA control cohort using the preoperative prostate biopsy data. CONCLUSION: The previously validated stratification of PSA outcome following radical prostatectomy (RP) using the percent of positive prostate biopsies in intermediate-risk patients is also clinically significant for men treated with external beam RT. The percent positive prostate biopsies should be considered in conjunction with the PSA level, biopsy Gleason score, and 1992 AJCC clinical T stage when counseling patients with newly diagnosed and clinically localized prostate cancer about PSA outcome following RP or external beam RT.     

Effect of cigarette smoking on biochemical outcome after permanent prostate brachytherapy

PURPOSE: Recent studies have suggested that cigarette smoking may be associated with an increased risk of death from prostate cancer. In this study, we evaluated the effect of cigarette smoking on the presentation and biochemical outcome after permanent prostate brachytherapy for prostate cancer. METHODS AND MATERIALS: A total of 582 patients underwent brachytherapy with generous periprostatic margins using either (103)Pd or (125)I with or without supplemental external beam radiotherapy between April 1995 and September 2000. Of the 582 patients, 178 (30.6%) had never smoked, 306 (52.6%) were former smokers, and 98 (16.8%) were current smokers. The median patient age was 67.9 years, and the median follow-up was 54.5 months. No patient was lost to follow-up. No patient underwent routine seminal vesicle biopsy or pathologic lymph node staging. The clinical, treatment, and dosimetric parameters evaluated included tobacco status, age, clinical stage, Gleason score, pretreatment prostate-specific antigen level, risk group, percentage of positive biopsies, ultrasound volume, isotope used, planning volume, hormonal status, use of external beam radiotherapy, and postimplant dosimetry (percentage of target volume receiving 100%, 150%, and 200% of the prescribed dose and percentage of prescribed dose covering 90% of the target volume). Biochemical outcome was determined using the American Society for Therapeutic Radiology and Oncology consensus definition. RESULTS: No differences in the clinical, treatment, or dosimetric parameters were identified, except that current smokers were statistically younger than those who had never smoked or former smokers (65.9 vs. 67.8 vs. 68.3 years, respectively, p = 0.016). Specifically, no relationship was discerned between tobacco history and risk group, supplemental external beam radiotherapy, choice of isotope, or use of hormonal therapy. The overall biochemical freedom from progression survival rate at 7 years was 96.2%, 95.6%, and 91.6% for patients who had never smoked, former smokers, and current smokers, respectively (p = 0.126). When stratified by risk group and hormonal status, tobacco consumption did not predict outcome, although a trend for poorer biochemical progression-free survival was noted in current smokers. The median prostate-specific antigen level for hormone-naive and hormonally manipulated disease-free patients was <0.1 ng/mL. In multivariate Cox regression analysis, Gleason score, pretreatment prostate-specific antigen level, risk group, and hormonal status were predictors of biochemical outcome. CONCLUSION: In this prostate brachytherapy cohort, tobacco consumption did not predict for risk group stratification or treatment approach. Although no statistically significant difference was found in biochemical progression-free survival, a trend for poorer biochemical outcome was demonstrated in current smokers.     

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

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

Clinical utility of the percentage of positive prostate biopsies in defining biochemical outcome after radical prostatectomy for patients with clinically localized prostate cancer.

PURPOSE: To determine the clinical utility of the percentage of positive prostate biopsies in predicting prostate-specific antigen (PSA) outcome after radical prostatectomy (RP) for men with PSA-detected or clinically palpable prostate cancer. METHODS: A Cox regression multivariable analysis was used to determine whether the percentage of positive prostate biopsies provided clinically relevant information about PSA outcome after RP in 960 men while accounting for the previously established risk groups that are defined according to pretreatment PSA level, biopsy Gleason score, and the 1992 American Joint Committee on Cancer (AJCC) clinical T stage. The findings were then tested using an independent surgical database that included data for 823 men. RESULTS: Controlling for the known prognostic factors, the percentage of positive prostate biopsies added clinically significant information (P <.0001) regarding time to PSA failure after RP. Specifically, 80% of the patients in the intermediate-risk group (1992 AJCC T2b, or biopsy Gleason 7 or PSA > 10 ng/mL and 相似文献   

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

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

Utility of the percentage of positive prostate biopsies in predicting PSA outcome after radiotherapy for patients with clinically localized prostate cancer

PURPOSE: To determine the utility of the percentage of positive prostate biopsies (PPPB) in predicting prostate-specific antigen (PSA) outcome after external beam radiotherapy alone. METHODS AND MATERIALS: The records of 750 clinical Stage T1 and T2 patients treated by external beam radiotherapy alone with a median follow-up of 80 months were reviewed. Of the 750 patients, 345 were eligible for analysis; 255 (74%) had undergone sextant biopsies, 28 (8%) <6 biopsies, and 62 (18%) >6 biopsies. The pretreatment PSA level (<10, 10-20, >20 ng/mL), biopsy Gleason score (2-6, 7, 8-10), and clinical stage (T1-T2a, T2b, T2c), uni- or bilateral positive biopsy, radiation dose, and PPPB were analyzed as potential predictors of PSA outcome. The PPPB data were analyzed as a continuous and as a categorical variable. RESULTS: PPPB was a significant predictor of the time to PSA failure on univariate analysis as a continuous (p = 0.0053) and as a categorical (<50% vs. >or=50%, p = 0.0077) variable. In multivariate analysis, a trend was noted for worse 5-year PSA failure-free survival based on PPPB >or=50% vs. <50% (p = 0.082). Sixty-four patients experienced biochemical failure according to the American Society for Therapeutic Radiology Oncology definition. The 5-year PSA failure-free survival rate was 79% vs. 69% (p = 0.02) and the clinical disease-free survival rate was 97% vs. 86% (p = 0.0004) for patients with <50% vs. >or=50% PPPB. PPPB was not a significant predictor for the time to PSA failure within the traditional risk groups (low, intermediate, and high) on multivariate analysis. CONCLUSION: PPPB was a predictor of post-external beam radiotherapy PSA outcome in clinically localized prostate cancer; but in this cohort it did not provide additional information beyond the traditional risk stratification schema.     

Comparison of biochemical failure definitions for permanent prostate brachytherapy

PURPOSE: To assess prostate-specific antigen (PSA) failure definitions for patients with Stage T1-T2 prostate cancer treated by permanent prostate brachytherapy. METHODS AND MATERIALS: A total of 2,693 patients treated with radioisotopic implant as solitary treatment for T1-T2 prostatic adenocarcinoma were studied. All patients had a pretreatment PSA, were treated at least 5 years before analysis, 1988 to 1998, and did not receive hormonal therapy before recurrence. Multiple PSA failure definitions were tested for their ability to predict clinical failure. RESULTS: Definitions which determined failure by a certain increment of PSA rise above the lowest PSA level to date (nadir + x ng/mL) were more sensitive and specific than failure definitions based on PSA doubling time or a certain number of PSA rises. The sensitivity and specificity for the nadir + 2 definition were 72% and 83%, vs. 51% and 81% for 3 PSA rises. The surgical type definitions (PSA exceeding an absolute value) could match this sensitivity and specificity but only when failure was defined as exceeding a PSA level in the 1-3 ng/mL range and only when patients were allowed adequate time to nadir. When failure definitions were compared by time varying covariate regression analysis, nadir + 2 ng/mL retained the best fit. CONCLUSIONS: For patients treated by permanent radioisotopic implant for prostate cancer, the definition nadir + 2 ng/mL provides the best surrogate for failure throughout the entire follow-up period, similar to patients treated by external beam radiotherapy. Therefore, the same PSA failure definition could be used for both modalities. For brachytherapy patients with long-term follow-up, at least 6 years, defining failure as exceeding an absolute PSA level in the 0.5 ng/mL range may be reasonable.     

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

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

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

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

A preliminary analysis of health-related quality of life in the first year after permanent source interstitial brachytherapy (PIB) for clinically localized prostate cancer

PURPOSE: To prospectively assess the health-related quality of life (HRQOL) and changes in HRQOL during the first year after permanent source interstitial brachytherapy (PIB). METHODS AND MATERIALS: Thirty-one men treated with PIB between September 1997 and March 1998 completed a quality of life (functional assessment of cancer therapy-prostate: FACT-P) and a urinary symptom questionnaire (international prostate symptom score: IPSS) prior to treatment (T0), 1 month (T1), 3 months (T3), 6 months (T6), and 12 months (T12) following PIB. All participants were treated with 125I alone. Repeated measures analyses of variance (ANOVA) were conducted on all quality of life and urinary outcome measures for all 31 patients at all time points. RESULTS: The median age of the study population was 66 (range 51-80). All men had clinical T1c-T2b prostate cancer. The Gleason score was < or =6 in 27/31 (87%). Median pretreatment PSA was 7.8 ng/ml (range 1.1-20.6). The mean score (and standard deviation) at T0, T1, T3, T6, and T12 for the FACT-P questionnaire are as follows: 140.5 (13.5), 132.7 (15.3), 137.2 (17.4), 140.1 (16.0), and 142.4 (15.3). For the global test across time, statistically significant differences were observed for the cumulative scores of FACT-P (p<0.0012). The decrease in HRQOL was most marked 1 month following PIB. Examination of the subscales within the FACT-P instrument demonstrated statistically significant changes over time for the following: physical well-being (PWB), functional well-being (FWB), and prostate cancer (PCS). By 3 months, all HRQOL measures had returned to near baseline. The mean score (and standard deviation) at T0, T1, T3, T6, and T12 for the IPSS questionnaire are as follows: 8.3 (5.5), 18.4 (8.0), 15.7 (7.4), 13.7 (7.4), and 10.2 (5.7). For the global test across time, statistically significant differences were observed for the IPSS scores (p<0.0001). The maximum increase in IPSS occurred 1 month following PIB. CONCLUSION: The results of this preliminary analysis suggest that clinically meaningful decreases in HRQOL, as measured by the FACT-P instrument, are evident within weeks after PIB. By 3 months, however, FACT-P scores return to near baseline levels. A validated instrument designed to measure urinary symptoms (IPSS) demonstrates that moderate to severe urinary symptoms persist for at least 3-6 months following PIB. One year following PIB, the scores on the FACT-P and IPSS questionnaires had returned to baseline.     

Prediction of PSA bounce after permanent prostate brachytherapy for localized prostate cancer

Background  

We aimed to calculate the frequency and features of the development of a prostate-specific antigen (PSA) bounce after prostate brachytherapy alone, to correlate the bounce with clinical and dosimetric factors and to identify factors that predict PSA bounce.     

Primary Gleason pattern does not impact survival after permanent interstitial brachytherapy for Gleason score 7 prostate cancer

BACKGROUND: The impact of primary Gleason pattern was determined on cause-specific (CSS), biochemical progression-free (bPFS), and overall survival (OS) after brachytherapy for Gleason score 7 prostate cancer. METHODS: From April 1995 to October 2003, 530 patients underwent brachytherapy for Gleason score 3+4 (n = 300) or Gleason 4+3 (n = 230) prostate cancer. All patients underwent brachytherapy more than 3 years before analysis. The median follow-up was 5.7 years. Of the 530 patients, 412 (77.7%) received supplemental external beam radiation therapy (XRT) and 177 (33.4%) received androgen deprivation therapy. bPFS was defined by a prostate-specific antigen (PSA) 相似文献