Identifying Differences Between Biochemical Failure and Cure: Incidence Rates and Predictors
ABSTRACT Patients treated with radiation therapy (RT) for prostate cancer were evaluated to estimate the length of time required to document biochemical cure (BC) after treatment and the variables associated with long-term treatment efficacy.
2,100 patients received RT alone for localized prostate carcinoma (external-beam RT, n = 1,504; brachytherapy alone, n = 241; or brachytherapy + pelvic radiation, n = 355). The median external-beam dose was 68.4 Gy, and the median follow-up time was 8.6 years. Biochemical failure (BF) was defined according to the Phoenix definition.
Biochemical failure was experienced by 685 patients (32.6%). The median times to BF for low-, intermediate-, and high-risk groups were 6.0, 5.6, and 4.5 years respectively (p < 0.001). The average annual incidence rates of BF for years 1-5, 5-10,11-15, and 16-20 in low-risk patients were 2.0%, 2.0%, 0.3%, and 0.06% (p < 0.001); for intermediate-risk patients, 4%, 3%, 0.3%, and 0% (p < 0.001); and for high-risk patients, 10.0%, 5.0%, 0.3%, and 0.3% (p < 0.001). After 5 years of treatment, 36.9% of all patients experienced BF. The percentage of total failures occurring during years 1-5, 5-10, 11-15, and 16-20 were 48.7%, 43.5%, 6.5%, and 1.3% for low-risk patients; 64.0%, 32.2%, 3.8%, and 0% for intermediate-risk patients; and 71.9%, 25.9%, 1.1%, and 1.1% for high-risk patients, respectively. Increasing time to nadir was associated with increased time to BF. On multivariate analysis, factors significantly associated with 10-year BC included prostate-specific antigen nadir and time to nadir.
The incidence rates for BF did not plateau until later than 10 years after treatment, suggesting that extended follow-up time is required to monitor patients after treatment. Prostate-specific antigen nadir and time to nadir have the strongest association with long-term BC.
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ABSTRACT: A lack of consensus and few data support testosterone replacement therapy (TRT) in hypogonadal men who have been treated for prostate cancer (CaP), particularly those who have received radiation therapy. We performed retrospective review of 13 hypogonadal men with CaP, treated with brachytherapy or external beam radiotherapy who were subsequently treated with testosterone (T) between 2006 and 2011. Serum T, free T (FT), estrogen (E), sex hormone-binding globulin (SHBG), prostate-specific antigen (PSA), hemoglobin (Hgb) and hematocrit (Hct) values were evaluated approximately every 3 months after TRT initiation up to 67 months of follow-up. Prostate biopsies demonstrated four men with Gleason (Gl) 6, 7 with Gl 7 and 2 with Gl 8 disease. Median (interquartile range) age at TRT initiation was 68.0 (62.0-77.0) years, initial T 178.0 (88.0-263.5) ng dl(-1), FT 10.1 (5.7-15.0) pg ml(-1) and PSA 0.30 (0.06-0.95) ng ml(-1). Median follow-up after TRT initiation was 29.7 months (range 2.3-67.3 months). At median follow-up, a significant increase in mean T (368.0 (281.3-591.0) ng dl(-1), P=0.012) and SHBG were observed, with no significant increases in Hgb, Hct, E, FT, or PSA (0.66 (0.16-1.35) ng ml(-1), P=0.345). No significant increases in PSA or CaP recurrences were observed at any follow-up interval. TRT in the setting of CaP after treatment with radiation therapy results in a rise in serum T levels and improvement in hypogonadal symptoms without evidence of CaP recurrence or progression.International Journal of Impotence Research advance online publication, 13 September 2012; doi:10.1038/ijir.2012.29.International journal of impotence research 09/2012; 25(1). DOI:10.1038/ijir.2012.29 · 1.37 Impact Factor
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ABSTRACT: Routine use of I-125 interstitial brachytherapy (BT) alone in intermediate risk (IR) prostate cancer is controversial. It is often combined with external beam radiotherapy (EBRT). The biochemical outcome of a large cohort of only IR disease treated with BT monotherapy is reported. Between 2003 and 2007, 615 patients with Memorial Sloan-Kettering Cancer Centre (MSKCC) defined IR disease (one risk factor only-T2b, or Gleason score (GS) 7, or raised initial PSA (iPSA) 10.1-20ng/ml) were treated with BT monotherapy. ASTRO (3 consecutive rises) and Phoenix (nadir plus 2) criteria defined biochemical failure. Potential prognostic factors (pre- and post-implant dosimetric indices, GS 3+4 versus 4+3, androgen deprivation therapy (ADT)) were analysed. Median follow-up was 5.0years. Forty-three patients had stage T2b, 180 had raised iPSA, 392 had GS 7 disease. ADT was received by 108 patients. The 5-year biochemical no evidence of disease (bNED) rates are 87.3% (by ASTRO), 88.6% (by Phoenix). Stratification by risk factor (T2b, GS7, raised iPSA) demonstrated raised iPSA to have poorer outcome only by Phoenix criteria (p=0.0002). Other potential prognostic variables were non-significant. Good rates of biochemical control can be achieved in the medium term with BT monotherapy in IR disease. Raised iPSA correlated with a poorer outcome.Radiotherapy and Oncology 07/2013; 109(2). DOI:10.1016/j.radonc.2013.05.030 · 4.86 Impact Factor
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ABSTRACT: 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. We retrospectively analyzed 2818 patients who underwent brachytherapy±external beam radiation therapy (EBRT)±androgen deprivation therapy (ADT). With median follow-up of 5.52years, 264 patients experienced PSA failure at a median time of 3.25years. Patients were stratified to early vs. late PSA failures at cutoffs of 1.5years, 3years, or 5years, and tested in univariate/multivariate analyses for freedom from DM, cause-specific survival (CSS), and overall survival (OS). 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 <3years, 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). Early PSA failure following radiation is a poor prognostic factor, as it is associated with increased DM, PCSM, and overall mortality.Radiotherapy and Oncology 11/2013; 110(2). DOI:10.1016/j.radonc.2013.11.003 · 4.86 Impact Factor