Adjuvant compared with early salvage radiation therapy (sRT) following radical prostatectomy (RP) has not been shown to reduce progression-free survival in randomized controlled trials. However, ...these trials might have missed a benefit in men with adverse pathology at RP given that these men were under-represented and immortal time bias might have been present; herein, we investigate this possibility.
We evaluated the impact of adjuvant versus early sRT on all-cause mortality (ACM) risk in men with adverse pathology defined as positive pelvic lymph nodes (pN1) or pGleason score 8-10 prostate cancer (PC) and disease extending beyond the prostate (pT3/4). We used a treatment propensity score to minimize potential treatment selection bias when estimating the causal effect of adjuvant versus early sRT on ACM risk and a sensitivity analysis to assess the impact that varying definitions of adverse pathology had on ACM risk adjusting for age at RP, PC prognostic factors, site, and the time-dependent use of post-RP androgen deprivation therapy.
After a median follow-up (interquartile range) of 8.16 (6.00-12.10) years, of the 26,118 men in the study cohort, 2,104 (8.06%) died, of which 539 (25.62%) were from PC. After excluding men with a persistent prostate-specific antigen, adjuvant compared with early sRT was associated with a significantly lower ACM risk among men with adverse pathology at RP when men with pN1 PC were excluded (0.33 0.13-0.85;
= .02) or included (0.66 0.44-0.99;
= .04).
Adjuvant radiation therapy should be considered in men with pN1 or pGleason score 8 to 10 and pT3/4 PC given the possibility that a significant reduction in ACM risk exists.
We evaluated whether men at risk for death from prostate cancer after radical prostatectomy can be identified using information available at diagnosis.
We studied 1095 men with localized prostate ...cancer to assess whether the rate of rise in the prostate-specific antigen (PSA) level--the PSA velocity--during the year before diagnosis, the PSA level at diagnosis, the Gleason score, and the clinical tumor stage could predict the time to death from prostate cancer and death from any cause after radical prostatectomy.
As compared with an annual PSA velocity of 2.0 ng per milliliter or less, an annual PSA velocity of more than 2.0 ng per milliliter was associated with a significantly shorter time to death from prostate cancer (P<0.001) and death from any cause (P=0.01). An increasing PSA level at diagnosis (P=0.01), a Gleason score of 8, 9, or 10 (P=0.02), and a clinical tumor stage of T2 (P<0.001) also predicted the time to death from prostate cancer. For men with an annual PSA velocity of more than 2.0 ng per milliliter, estimates of the risk of death from prostate cancer and death from any cause seven years after radical prostatectomy were also influenced by the PSA level, tumor stage, and Gleason score at diagnosis.
Men whose PSA level increases by more than 2.0 ng per milliliter during the year before the diagnosis of prostate cancer may have a relatively high risk of death from prostate cancer despite undergoing radical prostatectomy.
An update on androgen-deprivation therapy in prostate cancer and cardiovascular risk based on medical research brought by the American Heart Association, American Cancer Society, and American ...Urological Association, is presented.
This study aims at developing new macroseismic intensity attenuation models valid for Italy by exploiting the most updated macroseismic dataset and earthquakes catalogue, as well as the information ...obtained from a critical analysis of the most recent models in the literature. Several different attenuation models have been calibrated as a function of the moment magnitude (
Mw
) and epicentral distance from 16,260 intensity data points, that are related to 119 earthquakes occurred after 1900. According to trends and residuals analysis, the preferred calibrated intensity attenuation function is a Log-Linear model for epicentral distance (
R
epi
in km) and a linear model for
Mw
as:
I
MCS
=
1.81
-
2.61
L
o
g
R
-
0.0039
R
+
1.42
M
w
with pseudo hypocentral distance
R
=
R
epi
2
+
9.87
2
; the estimated standard deviation is
σ
= 0.75. Also noteworthy is another model for macroseismic intensity attenuation that proved to be as good as the best model and shows higher sensitivity to physical parameters, such as focal depth and magnitude, especially in the epicentral area. Performance of all calibrated models was also checked on an independent set of 15 post-1900 Italian earthquakes. One of the results of the present work is the opportunity to define earthquake scenarios (e.g. probabilistic seismic hazard maps) in terms of Macroseismic Intensity and its related standard deviation, avoiding the uncertainties due to the conversion of various ground shaking parameters into intensity values.
Interstitial radiation (implant) therapy is used to treat clinically localized adenocarcinoma of the prostate, but how it compares with other treatments is not known.
To estimate control of ...prostate-specific antigen (PSA) after radical prostatectomy (RP), external beam radiation (RT), or implant with or without neoadjuvant androgen deprivation therapy in patients with clinically localized prostate cancer.
Retrospective cohort study of outcome data compared using Cox regression multivariable analyses.
A total of 1872 men treated between January 1989 and October 1997 with an RP (n = 888) or implant with or without neoadjuvant androgen deprivation therapy (n = 218) at the Hospital of the University of Pennsylvania, Philadelphia, or RT (n = 766) at the Joint Center for Radiation Therapy, Boston, Mass, were enrolled.
Actuarial freedom from PSA failure (defined as PSA outcome).
The relative risk (RR) of PSA failure in low-risk patients (stage T1c, T2a and PSA level < or =10 ng/mL and Gleason score < or =6) treated using RT, implant plus androgen deprivation therapy, or implant therapy was 1.1 (95% confidence interval CI, 0.5-2.7), 0.5 (95% CI, 0.1-1.9), and 1.1 (95% CI, 0.3-3.6), respectively, compared with those patients treated with RP. The RRs of PSA failure in the intermediate-risk patients (stage T2b or Gleason score of 7 or PSA level >10 and < or =20 ng/mL) and high-risk patients (stage T2c or PSA level >20 ng/mL or Gleason score > or =8) treated with implant compared with RP were 3.1 (95% CI, 1.5-6.1) and 3.0 (95% CI, 1.8-5.0), respectively. The addition of androgen deprivation to implant therapy did not improve PSA outcome in high-risk patients but resulted in a PSA outcome that was not statistically different compared with the results obtained using RP or RT in intermediate-risk patients. These results were unchanged when patients were stratified using the traditional rankings of biopsy Gleason scores of 2 through 4 vs 5 through 6 vs 7 vs 8 through 10.
Low-risk patients had estimates of 5-year PSA outcome after treatment with RP, RT, or implant with or without neoadjuvant androgen deprivation that were not statistically different, whereas intermediate- and high-risk patients treated with RP or RT did better then those treated by implant. Prospective randomized trials are needed to verify these findings.
Accumulating reports of negative impacts of tourist activities on wildlife emphasize the importance of closely monitoring focal populations. Although some effects are readily noticed, more subtle ...ones such as changes in physiological functions of individuals might go overlooked. Based on evidence of altered physiology associated with ecotourism on Magellanic penguins Spheniscus magellanicus, here we performed an integrated assessment using a diverse physiological toolkit together with more traditional fitness-related measures to better understand mechanisms and potential consequences. Chicks exposed to tourism showed altered immune parameters and elevated flea prevalence, reinforcing previous findings. Tourism-exposed female, but not male, chicks also showed relatively lower hematocrit and plasma protein levels, providing evidence consistent with a sex-specific response to tourist visitation. Physiological alterations detected in tourism-exposed young chicks (week 1–2) were maintained and the effect on flea infestation increased during the study period (week 4–5 of post-hatch). Despite the effects on physiology, these did not seem to translate into immediate fitness costs. No detectable tourism effects were found on brood sex ratios, chick growth and body condition, and survival until week 5–6 post-hatch. We detected no effects on reproductive output and only a marginal effect on nest survival during incubation despite previous reports of tourism-associated alterations in stress indices of adults. This disconnection could result if the physiological changes are not strong enough to impact fitness, if effects balance each other out, or if changes are part of a copying strategy. Alternatively, the physiological alterations might only show impacts later in the brooding cycle or even after chick emancipation from their parents. Our results suggest that integrative monitoring of potential anthropogenic impacts on wildlife should include evaluation of physiological mechanisms and individual-level responses in populations exposed to human activities.
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•Tourism effects were assessed using physiological and more traditional fitness-related indices.•Tourism-exposed chicks showed altered immune parameters and higher flea prevalence.•Tourism-exposed female chicks also showed altered health parameters (sex-specific response).•Tourism effects were not detected on chick growth and survival during the studied period.•Potential explanations for the disconnection between the two types of indices are proposed.
To assess whether the time to prostate-specific antigen (PSA) nadir (TTN) has differential prognostic value in men who reach an undetectable vs detectable PSA nadir.
Two hundred and four men from a ...prospective randomized controlled trial involving radiation therapy with or without 6 months of androgen deprivation therapy in unfavorable risk Prostate cancer (CaP) at academic or community based centers in Massachusetts, enrolled between 1995 and 2001. Adjusted hazard ratios (AHR) of the risk of CaP-specific mortality calculated using Fine and Gray competing risk regression.
After a median follow-up of 18.17years, 160 men died; 30 (18.75%) of CaP. Among men with a PSA nadir ≥ 0.2ng/ml, a TTN < median (12 months) was significantly associated with an increased CaP-specific mortality-risk vs the median or more (AHR 5.07, 95% CI 2.10-12.23, P <.001); whereas this association was not observed among men with a PSA nadir of < 0.2ng/mL, (AHR 9.9, 95% CI 0.23-433.8, P = .23).
Men with both a short TTN and detectable PSA nadir could be considered for entry on randomized controlled trials at a novel entry point prior to PSA failure at the time of PSA nadir to completeplanned conventional androgen deprivation therapy vs that plus agent(s) shown to improve outcomes in men with or at high risk of having castrate-resistant CaP.
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