Impact of biochemical recurrence in prostate cancer among US veterans
ABSTRACT Among men treated for prostate cancer, increasing prostate-specific antigen (PSA) is known as biochemical failure or biochemical recurrence (BCR). The impact of BCR on subsequent mortality is uncertain, however, especially given competing causes of death.
To describe patterns of BCR and subsequent mortality, we conducted an observational study in a community-based, "high-comorbidity" setting of 623 US veterans diagnosed as having prostate cancer from 1991 to 1995 and receiving radical prostatectomy or radiation therapy. The main outcome measures were BCR, defined as a PSA level of 0.4 ng/mL or higher (treated with surgery) or "PSA nadir+2 ng/mL" (treated with radiation therapy), and prostate cancer mortality, determined through 2006.
With 5-, 10-, and 15-year follow-up periods, respectively (for all results shown herein), the cumulative incidence of BCR after prostatectomy (n=225) was 34%, 37%, and 37%; prostate cancer mortality among men who failed treatment (n=81) was 3%, 11%, and 21%. Among men receiving radiation therapy (n=398), the cumulative incidence of BCR was 35%, 46%, and 48%; prostate cancer mortality among those who failed treatment (n=161) was 11%, 20%, and 42%. Overall, BCR was associated with an increased risk of death from prostate cancer in the study population, but the individual probability of this outcome was relatively low.
Biochemical recurrence is associated with increased prostate cancer mortality, yet when BCR occurs only a minority of men subsequently die of their disease. The phrase "most men die with prostate cancer, not of it" applies to elderly veterans, even after failure of primary treatment. New strategies for defining and managing treatment failure in prostate cancer are needed.
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ABSTRACT: The electronic ground state of singly-charged cations of the cumulene family (H2CCnCH2, n=0,1,…) is doubly degenerate at the D2d geometry and is subject to an E⊗b or E⊗(b1⊕b2) Jahn–Teller effect. One of the Jahn–Teller active modes is the torsion, i.e., the disrotatory motion of the two terminal CH2 entities. The 2π periodicity of the torsional motion and the presence of maxima in the potential energy path along the torsional coordinate at planar geometries poses problems in the usual treatment of the Jahn–Teller effect of these cations, which relies on a Taylor expansion of the potential energy surfaces at the point of electronic degeneracy (D2d). A vibronic Hamiltonian has been derived to treat the E⊗b and E⊗(b1⊕b2) Jahn–Teller effects in molecules in which one of the Jahn–Teller active modes is the torsion or an internal rotation. The potential energy surfaces are expressed using Fourier series instead of Taylor series which enables a joint treatment of the Jahn–Teller effect and of hindered internal rotations. The resulting Hamiltonian has been used to predict the vibronic energy level structure of C2H4+ and C3H4+ and intensity distributions in the photoelectron spectra of C2H4 and C3H4. In particular, splittings arise from tunneling through the potential energy barrier at the D2h geometry. The predictions are compared with available spectroscopic data.Chemical Physics 11/2010; 377(1-3):66-77. DOI:10.1016/j.chemphys.2010.08.017 · 2.03 Impact Factor
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ABSTRACT: Until recently, patients with castration-resistant prostate cancer (CRPC) had limited therapeutic options once they became refractory to docetaxel chemotherapy, and no treatments improved survival. This changed in June 2010 when the Food and Drug Administration (FDA) approved cabazitaxel as a new option for patients with CRPC whose disease progresses during or after docetaxel treatment. For most of these patients, cabazitaxel will now replace mitoxantrone (a drug that was FDA-approved because of its palliative effects) as the treatment of choice for docetaxel-refractory disease. The approval of cabazitaxel was based primarily on the TROPIC trial, a large (n = 755) randomized Phase III study showing an overall median survival benefit of 2.4 months for men with docetaxel-pretreated metastatic CRPC receiving cabazitaxel (with prednisone) compared to mitoxantrone (with prednisone). Cabazitaxel is a novel tubulin-binding taxane that differs from docetaxel because of its poor affinity for P-glycoprotein (P-gp), an ATP-dependent drug efflux pump. Cancer cells that express P-gp become resistant to taxanes, and the effectiveness of docetaxel can be limited by its high substrate affinity for P-gp. Preclinical and early clinical studies show that cabazitaxel retains activity in docetaxel-resistant tumors, and this was confirmed by the TROPIC study. Common adverse events with cabazitaxel include neutropenia (including febrile neutropenia) and diarrhea, while neuropathy was rarely observed. Thus, the combination of cabazitaxel and prednisone is an important new treatment option for men with docetaxel-refractory metastatic CRPC, but this agent should be administered cautiously and with appropriate monitoring (especially in men at high risk of neutropenic complications).Drug Design, Development and Therapy 03/2011; 5(5):117-24. DOI:10.2147/DDDT.S13029 · 3.03 Impact Factor
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ABSTRACT: Localized prostate cancer is a slow growing tumor for many years for the majority of affected men. Low-dose rate brachytherapy (LDR-BT) is short-distance radiotherapy using low-energy radioactive sources. LDR-BT has been recommended for men with low risk localized prostate cancer. To assess the benefit and harm of LDR-BT compared to radical prostatectomy (RP), external beam radiotherapy (EBRT), and no primary therapy (NPT) in men with localized prostatic cancer. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1950), and EMBASE (from 1980) were searched in June 2010 as well as online trials registers and reference lists of reviews. Randomized, controlled trials comparing LDR-BT versus RP, EBRT, and NPT in men with clinically localized prostate cancer. Data on study methods, participants, treatment regimens, observation period and outcomes were recorded by two reviewers independently. We identified only one RCT (N = 200; mean follow up 68 months). This trial compared LDR-BT and RP. The risk of bias was deemed high. Primary outcomes (overall survival, cause-specific mortality, or metastatic-free survival) were not reported. Biochemical recurrence-free survival at 5 years follow up was not significantly different between LDR-BT (78/85 (91.8%)) and RP (81/89 (91.0%)); P = 0.875; relative risk 0.92 (95% CI: 0.35 to 2.42).For severe adverse events reported at 6 months follow up, results favored LDR-BT for urinary incontinence (LDR-BT 0/85 (0.0%) versus RP 16/89 (18.0%); P < 0.001; relative risk 0) and favored RP for urinary irritation (LDR-BT 68/85 (80.0%) versus RP 4/89 (4.5%); P < 0.001; relative risk 17.80, 95% CI 6.79 to 46.66). The occurrence of urinary stricture did not significantly differ between the treatment groups (LDR-BT 2/85 (2.4%) versus RP 6/89 (6.7%); P = 0.221; relative risk 0.35, 95% CI: 0.07 to 1.68). Long-term information was not available.We did not identify significant differences of mean scores between treatment groups for patient-reported outcomes function and bother as well as generic health-related quality of life. Low-dose rate brachytherapy did not reduce biochemical recurrence-free survival versus radical prostatectomy at 5 years. For short-term severe adverse events, low-dose rate brachytherapy was significantly more favorable for urinary incontinence, but radical prostatectomy was significantly more favorable for urinary irritation. Evidence is based on one RCT with high risk of bias.Cochrane database of systematic reviews (Online) 01/2011; DOI:10.1002/14651858.CD008871.pub2 · 5.94 Impact Factor