Biochemical outcome following external beam radiation therapy with or without androgen suppression therapy for patients with clinically localized prostate cancer (original) (raw)
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International Journal of Radiation Oncology*Biology*Physics, 2002
Purpose: To determine the efficacy of external beam radiotherapy (RT) as salvage treatment for prostate-specific antigen (PSA) failure or local recurrence after radical prostatectomy. Methods and Materials: Between 1991 and 1997, 98 patients underwent salvage RT to the prostatic bed at the Toronto Sunnybrook Regional Cancer Centre for PSA failure or local recurrence after radical prostatectomy. Thirty-six patients were treated for persistently detectable postoperative PSA levels (Group A), 26 for a delayed PSA rise (Group B), and 36 for palpable and/or biopsy-proven local recurrence (Group C). None had clinically apparent distant metastasis at the time of salvage RT. Freedom from PSA failure was defined as the maintenance of PSA <0.2 ng/mL. Cox regression analyses were performed to identify factors predictive of relapse. Results: The median follow-up from radical prostatectomy and RT was 5.11 and 4.21 years for Group A, 5.31 and 3.32 years for Group B, and 7.85 and 3.95 years for Group C, respectively. The initial PSA response rate was encouraging at a range of 86 -94%. The complete PSA response rate (PSA <0.2 ng/mL) was lower, however and ranged from 53% to 62%. The actuarial relapse-free rate, including freedom from PSA failure, at 4 years was 26%, 39%, and 14% for Groups A, B, and C, respectively. At the time of the last follow-up, 49, 20, and 1 patient had PSA failure alone, distant metastasis, and local progression, respectively. The actuarial survival rate at 4 years was 89%, 95%, and 94% for Groups A, B, and C, respectively. On Cox regression analysis, the significant predictors for relapse were PSA level before salvage RT and Gleason score for Group A, none for Group B, and margin status for Group C. Conclusion: The efficacy of salvage RT for PSA failure or local recurrence after RT was limited, reflected by very low relapse-free rates. Salvage RT appeared more efficacious for patients with a delayed PSA rise than for those with either persistently detectable postoperative PSA levels or clinically palpable local recurrence. Other strategies such as a combination of salvage RT and hormonal therapy need to be explored.
Cancer, 2004
BACKGROUNDThe goal of the current study was to analyze the prognostic value of early prostate-specific antigen (PSA) kinetics, with PSA assessed as reaching or failing to reach discrete threshold values at fixed time points during follow-up after external-beam radiotherapy (EBRT) for prostate carcinoma.The goal of the current study was to analyze the prognostic value of early prostate-specific antigen (PSA) kinetics, with PSA assessed as reaching or failing to reach discrete threshold values at fixed time points during follow-up after external-beam radiotherapy (EBRT) for prostate carcinoma.METHODSThe authors conducted a retrospective review of PSA follow-up for 839 patients treated between May 1987 and December 2000 at the Cleveland Clinic Foundation (Cleveland, OH). They also assessed the impact on bRFS of PSA levels lower than defined threshold values at given time points during follow-up.The authors conducted a retrospective review of PSA follow-up for 839 patients treated between May 1987 and December 2000 at the Cleveland Clinic Foundation (Cleveland, OH). They also assessed the impact on bRFS of PSA levels lower than defined threshold values at given time points during follow-up.RESULTSDuring a median follow-up of 74 months (range, 24–189 months), 540 patients (64.4%) maintained bRFS, whereas 299 patients (35.6%) did not maintain bRFS. The median nadir among patients with sustained bRFS was 0.4 ng/mL, with a median time to nadir of 28.9 months. Patients who did not maintain bRFS reached a median nadir of 1.3 ng/mL at a median of 15 months (P < 0.0001 for both nadir level and time to nadir). Reaching PSA thresholds of 3.0, 2.0, 1.0, 0.5, and 0.2 ng/mL at any time during follow-up was correlated with improved bRFS (P < 0.0001, each threshold). Patients whose PSA levels crossed the appropriate thresholds within 3 and 6 months of follow-up, irrespective of the time or level of eventual nadir, exhibited significantly improved bRFS when compared with patients whose PSA levels reached those thresholds at any time during follow-up and patients whose PSA levels never reached those thresholds (all thresholds: P < 0.0001).During a median follow-up of 74 months (range, 24–189 months), 540 patients (64.4%) maintained bRFS, whereas 299 patients (35.6%) did not maintain bRFS. The median nadir among patients with sustained bRFS was 0.4 ng/mL, with a median time to nadir of 28.9 months. Patients who did not maintain bRFS reached a median nadir of 1.3 ng/mL at a median of 15 months (P < 0.0001 for both nadir level and time to nadir). Reaching PSA thresholds of 3.0, 2.0, 1.0, 0.5, and 0.2 ng/mL at any time during follow-up was correlated with improved bRFS (P < 0.0001, each threshold). Patients whose PSA levels crossed the appropriate thresholds within 3 and 6 months of follow-up, irrespective of the time or level of eventual nadir, exhibited significantly improved bRFS when compared with patients whose PSA levels reached those thresholds at any time during follow-up and patients whose PSA levels never reached those thresholds (all thresholds: P < 0.0001).CONCLUSIONSDespite previous conclusions that early PSA assessment may lack prognostic value, the data obtained in the current study suggest that the kinetics of early PSA decline is predictive of long-term bRFS when assessed using a time-and–PSA threshold model. After EBRT for prostate carcinoma, PSA levels below various discrete PSA thresholds were indicative of statistically meaningful long-term outcome differences between experimental arms as early as 90 days after radiotherapy. If the time-and–PSA threshold model is shown to be predictive of prostate carcinoma mortality as well, then it may allow the scientific community to evaluate promising treatment concepts and technologies at a highly accelerated pace. Cancer 2004. © 2004 American Cancer Society.Despite previous conclusions that early PSA assessment may lack prognostic value, the data obtained in the current study suggest that the kinetics of early PSA decline is predictive of long-term bRFS when assessed using a time-and–PSA threshold model. After EBRT for prostate carcinoma, PSA levels below various discrete PSA thresholds were indicative of statistically meaningful long-term outcome differences between experimental arms as early as 90 days after radiotherapy. If the time-and–PSA threshold model is shown to be predictive of prostate carcinoma mortality as well, then it may allow the scientific community to evaluate promising treatment concepts and technologies at a highly accelerated pace. Cancer 2004. © 2004 American Cancer Society.
Radiotherapy and Oncology, 2014
Background and purpose: We investigated whether earlier PSA failure following prostate brachytherapy is associated with increased rates of distant metastases (DM), prostate cancer-specific mortality (PCSM), and overall mortality. Materials and methodsMaterials and methods: We retrospectively analyzed 2818 patients who underwent brachytherapy ± external beam radiation therapy (EBRT) ± androgen deprivation therapy (ADT). With median follow-up of 5.52 years, 264 patients experienced PSA failure at a median time of 3.25 years. Patients were stratified to early vs. late PSA failures at cutoffs of 1.5 years, 3 years, or 5 years, and tested in univariate/multivariate analyses for freedom from DM, cause-specific survival (CSS), and overall survival (OS). Results: Among patients with PSA failures, 69 (26%) patients experienced DM, 47 (18%) PCSM, and 56 (21%) deaths from other causes. Patients with rapid PSA failures demonstrated increased rates of DM, PCSM, and overall mortality, despite higher total BED and longer ADT. In multivariate analysis with a PSA failure interval <3 years, the hazard ratio (HR) for DM was 3.92 (95% CI: 2.34-6.55; p = 0.000); HR for PCSM was 2.79 (95% CI: 1.45-5.38; p = 0.002); and HR for overall mortality was 2.28 (95% CI: 1.50-3.48; p = 0.000). Conclusion: Early PSA failure following radiation is a poor prognostic factor, as it is associated with increased DM, PCSM, and overall mortality.
Strahlentherapie und Onkologie, 2011
The optimal dose for salvage radiotherapy (SRT) after radical prostatectomy (RP) is still not defined. It should be at least 66 Gy. In the present study, the suitability of PSA regression as a selection criterion for an SRT dose escalation to 70.2 Gy was examined. Patients and Methods: Between 1997 and 2007, 301 prostate cancer patients received SRT after RP at the Charité -University Medicine Berlin, Campus Benjamin Franklin. None of the patients had antihormone therapy prior to SRT. A total of 234 patients received 66.6 Gy. From 2002 on, 67 patients with a PSA decrease during SRT were irradiated with 70.2 Gy. The influence of this selection and dose escalation on freedom from biochemical progression (bNED) was analyzed. Results: The median follow-up of the whole group was 30 months, the median pre-SRT PSA was 0.28 ng/ml. Of the patients, 27% (82/301) developed biochemical progression, 31% from the 66.6 Gy cohort (73/292) and 13% from the 70.2 Gy cohort (9/67) (p = 0.01). The calculated 2-years bNED was 74% for the whole group, 88% vs. 71% after 70.2 Gy and 66.6 Gy, respectively (p = 0.01). In a multivariate analysis, the total dose (p = 0.017), the re-achievement of an undetectable PSA after SRT (p = 0.005), and the infiltration of the seminal vesicles (p = 0.049) were independent parameters of bNED. Conclusion: Our analysis suggests that patient selection during SRT for a dose escalation to 70.2 Gy can improve the freedom from biochemical progression in patients with SRT after RP.
Early salvage radiotherapy for patients with PSA relapse after radical prostatectomy
Journal of Cancer Research and Clinical Oncology, 2009
Purpose To assess the eVectiveness of early salvage radiotherapy (RT) for patients with prostate-speciWc antigen (PSA) relapse after radical prostatectomy (RP) retrospectively. Methods Fifty-one patients underwent salvage RT for biochemical relapse of prostate cancer initially treated with RP. All patients had persistent or rising PSA >0.20 ng/ml at some point after surgery, or three successive PSA elevations after a postoperative nadir if PSA was •0.20 ng/ml. Most (96%) of pre-RT PSA were less or equal to 0.50 ng/ ml, and median value was 0.25 ng/ml (range, 0.05-0.90 ng/ ml). Median RT dose was 60 Gy (range, 50-66 Gy). Multivariate Cox regression analysis was performed for PSA before RP and salvage RT, margin status, seminal vesicle involvement, extracapsular invasion, Gleason score, PSA doubling time (PSADT), and RT dose to identify signiWcant predictors of biochemical outcome. Results Median follow-up was 36 months. The 3-year biochemical no evidence of disease rate (bNED) was 55.1%. On multivariate analysis only the following factors were signiWcantly associated with improved bNED: PSADT >3.0 months (P = 0.008), Gleason score •7 (P = 0.01), and RT dose ¸60 Gy (P = 0.028). Conclusions Although a total dose of 60 Gy was eVective at a low pre-RT PSA levels with short follow-up, an RT dose ¸60 Gy resulted in superior biochemical outcomes even in patients with a pre-RT PSA •0.50 ng/ml.
International Journal of Radiation Oncology*Biology*Physics, 2004
Methods and Materials: Nine participating institutions submitted data on 4839 patients treated between 1986 and 1995 for Stage T1b-T2cN0-NxM0 prostate cancer. All patients were treated definitively with RT alone to doses >60 Gy, without neoadjuvant or planned adjuvant androgen suppression. A total of 4833 patients with a median follow-up of 6.3 years met the criteria for analysis. Two endpoints were considered: (1) PSA-DFS, defined as freedom from PSA failure (American Society for Therapeutic Radiology and Oncology definition), initiation of androgen suppression after completion of RT, or documented local or distant failure; and (2) DMFS, defined as freedom from clinically apparent distant failure. In patients with failure, nPSA was defined as the lowest PSA measurement before any failure. In patients without failure, nPSA was the lowest PSA measurement during the entire follow-up period. T nPSA was calculated from the completion of RT to the nPSA date. Results: A greater nPSA level and shorter T nPSA were associated with decreased PSA-DFS and DMFS in all patients and in all risk categories (low [Stage T1b, T1c, or T2a, Gleason score <6, and PSA level <10 ng/mL], intermediate [Stage T1b, T1c, or T2a, Gleason score <6, and PSA level >10 but <20 ng/mL, or Stage T2b or T2c, Gleason score <6, and PSA level <20 ng/mL, or Gleason score 7 and PSA level <20 ng/mL], and high [Gleason score 8 -10 or PSA level >20 ng/mL]), regardless of RT dose. The 8-year PSA-DFS and DMFS rate for patients with nPSA <0.5 ng/mL was 75% and 97%; nPSA >0.5 but <1.0 ng/mL, 52% and 96%; nPSA >1.0 but <2.0 ng/mL, 40% and 91%; and nPSA >2.0 ng/mL, 17% and 73%, respectively. The 8-year PSA-DFS and DMFS rate for patients with T nPSA <6 months was 27% and 66%; T nPSA >6 but <12 months, 31% and 85%; T nPSA >12 but <24 months, 42% and 94%; and T nPSA >24 months, 75% and 99%, respectively. A shorter T nPSA was associated with decreased PSA-DFS and DMFS, regardless of the nPSA. Both nPSA and T nPSA were significant predictors of PSA-DFS and DMFS in multivariate models incorporating clinical stage, Gleason score, initial PSA level, and RT dose. The significance of nPSA and T nPSA was supported by landmark analysis, as well as by analysis of nPSA and T nPSA as time-dependent covariates. A dose >70 Gy was associated with a lower nPSA level and longer T nPSA in all risk categories, and a greater dose was significantly associated with greater PSA-DFS and DMFS in multivariate analysis. Regression analysis confirmed that higher clinical stage, Gleason score, and initial PSA were associated with a greater nPSA level.
International Journal of Radiation Oncology*Biology*Physics, 2003
. Methods: Nine institutions combined data on 4839 patients with stage T1 and T2 adenocarcinoma of the prostate who received >60 Gy external beam radiation therapy (RT) as sole treatment. No patient received neoadjuvant androgen deprivation or planned adjuvant androgen deprivation. Of the 4839 patients, 1325 were treated in 1994 and 1995; 1061 were treated with <72 Gy and 264 with >72 Gy. The median RT doses for the <72 Gy and the >72 Gy groups were 68.4 Gy and 75.6 Gy, respectively. The median follow-up for the <72 Gy and the >72 Gy groups were 5.8 and 5.7 years, respectively. Risk groups, defined on the basis of T stage, pretherapy PSA level, and biopsy Gleason score (GS), were as follows: low risk-T1b, T1c, T2a, GS <6 and PSA <10 ng/mL; intermediate risk-T1b, T1c, T2a, GS <6 and PSA >10 ng/mL but <20 ng/mL or T2b, GS <6 and PSA <20 ng/mL or GS 7 and PSA <20 ng/mL; high risk-GS 8 -10 or PSA >20 ng/mL. The endpoint for outcome analysis was PSA-DFS at 5 years after therapy using the American Society for Therapeutic Radiology and Oncology failure definition. Results: Patients receiving >72 Gy had significantly more advanced cancers. The proportion of stage T2b/T2c cancers in the >72 Gy group was 42% compared with 32% in the <72 Gy group (p ؍ 0.027). The mean pretherapy PSA was 11.4 ng/mL in the >72 Gy group compared with 10.7 ng/mL in the <72 Gy group (p ؍ 0.001). The proportion of GS >8 cancers in the >72 Gy group was 9% compared with 7% in the <72 Gy group (p ؍ 0.309). Overall, 15% of patients receiving <72 Gy had high-risk disease, compared with 22% of patients receiving >72 Gy (p ؍ 0.034). The >72 Gy group had a greater number of follow-up PSA levels (mean 10.6/patient) compared with the <72 Gy group (mean 9.6/patient) (p ؍ 0.007). For all 1325 patients, the 5-and 8-year PSA-DFS estimates were 64% and 62%, respectively. The 5-year PSA-DFS estimates for <72 Gy vs. >72 Gy were 63% vs. 69%, respectively (p ؍ 0.046). Multivariate analysis for factors affecting PSA-DFS was performed for all cases using the following variables: pretherapy PSA (continuous), biopsy GS (continuous), stage (T1 vs. T2), radiation dose (continuous), and radiation technique (three-dimensional conformal vs. conventional). Pretreatment PSA (p < 0.001, chi-square 112.2), GS (p < 0.001, chi-square 12.8), radiation dose (p < 0.001, chi-square 13.5), and stage (p ؍ 0.007, chi-square 7.2) were independent predictors of outcome. Radiotherapy technique was not (p ؍ 0.50). Conclusion: Differences in PSA-DFS estimates observed in multiple retrospective series have been attributed to differences in follow-up duration between patients treated to conventional doses (longer follow-up intervals) and those treated to higher doses (shorter follow-up intervals). In this report, the median follow-up duration in the >72 Gy group was essentially identical to the <72 Gy group, because the study included a large number of patients treated consecutively during a narrow time range (1994 -1995). With similar follow-up duration, higher than conventional radiotherapy doses were associated with improved PSA-DFS when controlled for the influence of pretreatment PSA levels, biopsy GS, and clinical T stage.
Clinical Oncology, 1997
There has been substantial interest in the effect of radiation therapy upon serum prostate specific antigen (PSA) levels in patients managed by radiation therapy and their ability to predict the eventual outcome. At our institute, an observational prospective longitudinal study was begun in 1989 to identify prognostic factors for biochemical relapse from among several variables, including PSA levels measured prior to treatment, during treatment, and post-treatment, and to summarize what happens to PSA levels over the course of treatment with radical radiation therapy. A total of 142 patients with adenocarcinoma of the prostate (T1-4, No, Mo) were radically irradiated (6-7 weeks) between February 1989 and January 1991. Serum PSA levels were recorded weekly during radiation therapy in 117 patients. Of these 117, weekly PSA measurements ranged in completeness from 95 to 113 cases. A number of statistical tests were performed on the data with investigative/ exploratory intent. There were 60 biochemical relapses documented in the whole group of 142 patients, with a maximum follow-up of 4.6 years and median follow-up of 3.3 years. Of the candidate prognostic variables tested by univariate analysis, the following emerged as statistically significant (i.e. P<0.05): each of the four pretreatment factors (absolute PSA value, dichotomous PSA (normal versus above normal), T category and Gleason score); the treatment variables namely, the end-of-treatment PSA, the slope of PSA, and the absolute change in PSA from pretreatment to the end of treatment; and, among post-treatment variables, the first follow-up PSA, the absolute change in PSA from pretreatment to first follow-up, and the return to normal of an above-normal pretreatment PSA by first follow-up. The majority of these factors were then subjected to multivariate Cox proportional hazards (PH) regression analyses. The end-of-treatment PSA and T category were consistently identified as independently statistically significant factors associated with biochemical relapse. The Gleason score was selected less consistently, and never when