Purpose
Extraprostatic disease will be manifest in one third of men after radical prostatectomy. We present long-term followup of a randomized clinical trial of radiotherapy to reduce risk of subsequent metastatic disease and death.
Materials and Methods
431 men with pT3N0M0 prostate cancer were randomized to 60–64 Gy adjuvant radiotherapy or observation. The primary study endpoint was metastasis-free survival.
Results
Of 425 eligible men, 211 were randomized to observation and 214 to adjuvant radiation. Of those receiving observation, 70 ultimately received radiotherapy. Metastatic-free survival was significantly less with radiotherapy (93 events out of 214 on the RT arm, 114 events out of 211 on observation, Hazard Ratio [HR] 0.71, 95% confidence interval [CI] 0.54, 0.94; p=0.016). Survival was improved significantly with adjuvant radiation (88 deaths out of 214 on the RT arm, 110 deaths out of 211 on observation HR 0.72, 95% CI 0.55,0.96; p=0.023).
Conclusions
Adjuvant radiotherapy after radical prostatectomy for a man with pT3N0M0 prostate cancer significantly reduces the risk of metastasis and increases survival.
In men who had undergone radical prostatectomy for pathologically advanced prostate cancer, adjuvant radiotherapy resulted in significantly reduced risk of PSA relapse and disease recurrence, although the improvements in metastasis-free survival and overall survival were not statistically significant. Trial Registration clinicaltrials.gov Identifier: NCT00394511.
A recently developed matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) method to spatially profile the location and distribution of multiple N-linked glycan species in frozen tissues has been extended and improved for the direct analysis of glycans in clinically derived formalin-fixed paraffin-embedded (FFPE) tissues. Formalin-fixed tissues from normal mouse kidney, human pancreatic and prostate cancers, and a human hepatocellular carcinoma tissue microarray were processed by antigen retrieval followed by on-tissue digestion with peptide N-glycosidase F. The released N-glycans were detected by MALDI-IMS analysis, and the structural composition of a subset of glycans could be verified directly by on-tissue collision-induced fragmentation. Other structural assignments were confirmed by off-tissue permethylation analysis combined with multiple database comparisons. Imaging of mouse kidney tissue sections demonstrates specific tissue distributions of major cellular N-linked glycoforms in the cortex and medulla. Differential tissue distribution of N-linked glycoforms was also observed in the other tissue types. The efficacy of using MALDI-IMS glycan profiling to distinguish tumor from non-tumor tissues in a tumor microarray format is also demonstrated. This MALDI-IMS workflow has the potential to be applied to any FFPE tissue block or tissue microarray to enable higher throughput analysis of the global changes in N-glycosylation associated with cancers.
ABSTRACT. Using the best-fitting multiple logistic regression equation, a 100-point increase in pAkt staining resulted in a 160% increase in the odds of being a PSA failure. There was decreased staining for pERK in PSA failures versus non-failures: a 100-point decrease resulted in an 80% increase in the odds of being a PSA failure. Each of these effects assumed the other biomarker was held constant. The area under the receiver-operating characteristic curve for these two biomarkers predicting PSA failure was 0.84, indicating excellent discrimination between PSA failure and non-failure cases. These data indicate that increased pAkt, alone or together with decreased pERK, is an important predictor of probability of PSA failure. However, pERK alone was not a significant predictor of PSA failure.
BACKGROUNDRecent studies of men with prostate carcinoma suggest that obesity may be associated with more advanced‐stage disease and lower overall survival rates. One possible link between body mass index (BMI) and prostate carcinoma prognosis may be disease ascertainment. Prostate‐specific antigen (PSA) is widely used to screen for prostate carcinoma.METHODSThe authors examined the association between BMI and PSA in a population‐based study of 2779 men without prostate carcinoma. Between 2001 and 2004, these men were enrolled in a study sponsored by the San Antonio Center of Biomarkers of Risk, a clinical and epidemiologic center of the Early Detection Research Network of the National Cancer Institute.RESULTSThe mean PSA value decreased in a linear fashion with an increase in BMI category, from 1.01 ng/mL in normal weight men to 0.69 ng/mL in obese (Class III) men, after adjusting for race/ethnicity and age.CONCLUSIONSLower levels of PSA in obese and overweight men could mask biologically consequential prostate carcinoma. Cancer 2005. Published 2005 by the American Cancer Society.
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