The long-term risk of prostate cancer-specific mortality (PCSM) after radical prostatectomy is poorly defined for patients treated in the era of widespread prostate-specific antigen (PSA) screening. ...Models that predict the risk of PCSM are needed for patient counseling and clinical trial design.
A multi-institutional cohort of 12,677 patients treated with radical prostatectomy between 1987 and 2005 was analyzed for the risk of PCSM. Patient clinical information and treatment outcome was modeled using Fine and Gray competing risk regression analysis to predict PCSM.
Fifteen-year PCSM and all-cause mortality were 12% and 38%, respectively. The estimated PCSM ranged from 5% to 38% for patients in the lowest and highest quartiles of predicted risk of PSA-defined recurrence, based on a popular nomogram. Biopsy Gleason grade, PSA, and year of surgery were associated with PCSM. A nomogram predicting the 15-year risk of PCSM was developed, and the externally validated concordance index was 0.82. Neither preoperative PSA velocity nor body mass index improved the model's accuracy. Only 4% of contemporary patients had a predicted 15-year PCSM of greater than 5%.
Few patients will die from prostate cancer within 15 years of radical prostatectomy, despite the presence of adverse clinical features. This favorable prognosis may be related to the effectiveness of radical prostatectomy (with or without secondary therapy) or the low lethality of screen-detected cancers. Given the limited ability to identify contemporary patients at substantially elevated risk of PCSM on the basis of clinical features alone, the need for novel markers specifically associated with the biology of lethal prostate cancer is evident.
We present sample transfer instrumentation and integrated protocols for the preparation and atom probe characterization of environmentally-sensitive materials. Ultra-high vacuum cryogenic suitcases ...allow specimen transfer between preparation, processing and several imaging platforms without exposure to atmospheric contamination. For expedient transfers, we installed a fast-docking station equipped with a cryogenic pump upon three systems; two atom probes, a scanning electron microscope / Xe-plasma focused ion beam and a N2-atmosphere glovebox. We also installed a plasma FIB with a solid-state cooling stage to reduce beam damage and contamination, through reducing chemical activity and with the cryogenic components as passive cryogenic traps. We demonstrate the efficacy of the new laboratory protocols by the successful preparation and transfer of two highly contamination- and temperature-sensitive samples-water and ice. Analysing pure magnesium atom probe data, we show that surface oxidation can be effectively suppressed using an entirely cryogenic protocol (during specimen preparation and during transfer). Starting with the cryogenically-cooled plasma FIB, we also prepared and transferred frozen ice samples while avoiding significant melting or sublimation, suggesting that we may be able to measure the nanostructure of other normally-liquid or soft materials. Isolated cryogenic protocols within the N2 glove box demonstrate the absence of ice condensation suggesting that environmental control can commence from fabrication until atom probe analysis.
Objectives
To determine if the presence of adverse pathological features in patients eligible for active surveillance (AS) are prognostic of poor oncological outcomes, independent of pretreatment ...risk.
Patients and Methods
A retrospective analysis was performed on patients who underwent radical prostatectomy (RP) at two institutions (Cleveland Clinic Foundation and Memorial Sloan Kettering Cancer Center) between 1987 and 2008, and who had subsequent follow‐up. Rates of biochemical recurrence, metastasis and death from prostate cancer were compared amongst patients with adverse pathological features (Gleason score ≥7, ≥pT3, or lymph node invasion) based on D'Amico clinical risk (low vs intermediate/high). We also compared survival outcomes between patients with and without pathological upgrading/upstaging amongst D'Amico low‐risk patients. Univariate and multivariable Cox regression models were used to assess the association between clinical risk, pathological reclassification, and oncological outcomes.
Results
We identified 16 341 patients who underwent RP, of whom 6 371 were clinically low‐risk. Adverse outcomes in men with adverse pathological features were significantly lower in those with low clinical risk, with an ~50% and ~70% reduction in the risk of metastasis and death, respectively. Only pathological upgrading/upstaging to Gleason score ≥8, seminal vesicle invasion, and lymph node invasion from clinical low‐risk disease, were associated with adverse outcomes. However, these types of reclassification were rare.
Conclusion
Clinical low‐risk patients with pathological upgrading/upstaging have substantially lower rates of important oncological outcomes compared to those with higher pretreatment risk and not substantially different than low‐risk patients without pathological upgrading/upstaging. These results call into question the use of this endpoint to counsel patients about the merits and risks of AS.
Oxygen is commonly administered to patients with ST-elevation-myocardial infarction despite previous studies suggesting a possible increase in myocardial injury as a result of coronary ...vasoconstriction and heightened oxidative stress.
We conducted a multicenter, prospective, randomized, controlled trial comparing oxygen (8 L/min) with no supplemental oxygen in patients with ST-elevation-myocardial infarction diagnosed on paramedic 12-lead ECG. Of 638 patients randomized, 441 patients had confirmed ST-elevation-myocardial infarction and underwent primary end-point analysis. The primary end point was myocardial infarct size as assessed by cardiac enzymes, troponin I, and creatine kinase. Secondary end points included recurrent myocardial infarction, cardiac arrhythmia, and myocardial infarct size assessed by cardiac magnetic resonance imaging at 6 months. Mean peak troponin was similar in the oxygen and no oxygen groups (57.4 versus 48.0 μg/L; ratio, 1.20; 95% confidence interval, 0.92-1.56; P=0.18). There was a significant increase in mean peak creatine kinase in the oxygen group compared with the no oxygen group (1948 versus 1543 U/L; means ratio, 1.27; 95% confidence interval, 1.04-1.52; P=0.01). There was an increase in the rate of recurrent myocardial infarction in the oxygen group compared with the no oxygen group (5.5% versus 0.9%; P=0.006) and an increase in frequency of cardiac arrhythmia (40.4% versus 31.4%; P=0.05). At 6 months, the oxygen group had an increase in myocardial infarct size on cardiac magnetic resonance (n=139; 20.3 versus 13.1 g; P=0.04).
Supplemental oxygen therapy in patients with ST-elevation-myocardial infarction but without hypoxia may increase early myocardial injury and was associated with larger myocardial infarct size assessed at 6 months.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01272713.
Purpose Long-term prostate cancer specific mortality after radical prostatectomy is poorly defined in the era of widespread screening. An understanding of the treated natural history of screen ...detected cancers and the pathological risk factors for prostate cancer specific mortality are needed for treatment decision making. Materials and Methods Using Fine and Gray competing risk regression analysis we modeled clinical and pathological data, and followup information on 11,521 patients treated with radical prostatectomy at a total of 4 academic centers from 1987 to 2005 to predict prostate cancer specific mortality. The model was validated on 12,389 patients treated at a separate institution during the same period. Median followup in the modeling and validation cohorts was 56 and 96 months, respectively. Results The overall 15-year prostate cancer specific mortality rate was 7%. Primary and secondary Gleason grade 4–5 (each p <0.001), seminal vesicle invasion (p <0.001) and surgery year (p = 0.002) were significant predictors of prostate cancer specific mortality. A nomogram predicting 15-year prostate cancer specific mortality based on standard pathological parameters was accurate and discriminating with an externally validated concordance index of 0.92. When stratified by patient age at diagnosis, the 15-year prostate cancer specific mortality rate for pathological Gleason score 6 or less, 3 + 4, 4 + 3 and 8–10 was 0.2% to 1.2%, 4.2% to 6.5%, 6.6% to 11% and 26% to 37%, respectively. The 15-year prostate cancer specific mortality risk was 0.8% to 1.5%, 2.9% to 10%, 15% to 27% and 22% to 30% for organ confined cancer, extraprostatic extension, seminal vesicle invasion and lymph node metastasis, respectively. Only 3 of 9,557 patients with organ confined, pathological Gleason score 6 or less cancer died of prostate cancer. Conclusions Poorly differentiated cancer and seminal vesicle invasion are the prime determinants of prostate cancer specific mortality after radical prostatectomy. The prostate cancer specific mortality risk can be predicted with remarkable accuracy after the pathological features of prostate cancer are known.
Persistent changes in tree mortality rates can alter forest structure, composition, and ecosystem services such as carbon sequestration. Our analyses of longitudinal data from unmanaged old forests ...in the western United States showed that background (noncatastrophic) mortality rates have increased rapidly in recent decades, with doubling periods ranging from 17 to 29 years among regions. Increases were also pervasive across elevations, tree sizes, dominant genera, and past fire histories. Forest density and basal area declined slightly, which suggests that increasing mortality was not caused by endogenous increases in competition. Because mortality increased in small trees, the overall increase in mortality rates cannot be attributed solely to aging of large trees. Regional warming and consequent increases in water deficits are likely contributors to the increases in tree mortality rates.
A postoperative nomogram for prostate cancer recurrence after radical prostatectomy (RP) has been independently validated as accurate and discriminating. We have updated the nomogram by extending the ...predictions to 10 years after RP and have enabled the nomogram predictions to be adjusted for the disease-free interval that a patient has maintained after RP.
Cox regression analysis was used to model the clinical information for 1,881 patients who underwent RP for clinically-localized prostate cancer by two high-volume surgeons. The model was externally validated separately on two independent cohorts of 1,782 patients and 1,357 patients, respectively. Disease progression was defined as a rising prostate-specific antigen (PSA) level, clinical progression, radiotherapy more than 12 months postoperatively, or initiation of systemic therapy.
The 10-year progression-free probability for the modeling set was 79% (95% CI, 75% to 82%). Significant variables in the multivariable model included PSA (P = .002), primary (P < .0001) and secondary Gleason grade (P = .0006), extracapsular extension (P < .0001), positive surgical margins (P = .028), seminal vesicle invasion (P < .0001), lymph node involvement (P = .030), treatment year (P = .008), and adjuvant radiotherapy (P = .046). The concordance index of the nomogram when applied to the independent validation sets was 0.81 and 0.79.
We have developed and validated as a robust predictive model an enhanced postoperative nomogram for prostate cancer recurrence after RP. Unique to predictive models, the nomogram predictions can be adjusted for the disease-free interval that a patient has achieved after RP.
An existing preoperative nomogram predicts the probability of prostate cancer recurrence, defined by prostate-specific antigen (PSA), at 5 years after radical prostatectomy based on clinical stage, ...serum PSA, and biopsy Gleason grade. In an updated and enhanced nomogram, we have extended the predictions to 10 years, added the prognostic information of systematic biopsy results, and enabled the predictions to be adjusted for the year of surgery. Cox regression analysis was used to model the clinical information for 1978 patients treated by two high-volume surgeons from our institution. The nomogram was externally validated on an independent cohort of 1545 patients with a concordance index of 0.79 and was well calibrated with respect to observed outcome. The inclusion of the number of positive and negative biopsy cores enhanced the predictive accuracy of the model. Thus, a new preoperative nomogram provides robust predictions of prostate cancer recurrence up to 10 years after radical prostatectomy.
To provide recommendations on appropriate uses for serum markers of germ cell tumors (GCTs).
Searches of MEDLINE and EMBASE identified relevant studies published in English. Primary outcomes included ...marker accuracy to predict the impact of decisions on outcomes. Secondary outcomes included proportions of patients with elevated markers and statistical tests of elevations as prognostic factors. An expert panel developed consensus guidelines based on data from 82 reports.
No studies directly compared outcomes of decisions with versus without marker assays. The search identified few prospective studies and no randomized controlled trials; most were retrospective series. Lacking data on primary outcomes, most Panel recommendations are based on secondary outcomes (relapse rates and time to relapse).
The Panel recommended against using markers to screen for GCTs, to decide whether orchiectomy is indicated, or to select treatment for patients with cancer of unknown primary. To stage patients with testicular nonseminomas, the Panel recommended measuring three markers (alpha-fetoprotein AFP, human chorionic gonadotropin hCG, and lactate dehydrogenase LDH) before and after orchiectomy and before chemotherapy for those with extragonadal nonseminomas. They also recommended measuring AFP and hCG shortly before retroperitoneal lymph node dissection and at the start of each chemotherapy cycle for nonseminoma, and periodically to monitor for relapse. The Panel recommended measuring postorchiectomy hCG and LDH for patients with seminoma and preorchiectomy elevations. They recommended against using markers to guide or monitor treatment for seminoma or to detect relapse in those treated for stage I. However, they recommended measuring hCG and AFP to monitor for relapse in patients treated for advanced seminoma.
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