There is little evidence that calculation of PSA velocity or doubling time in untreated patients provides predictive information beyond that provided by absolute PSA level alone. We see no justification for the use of PSA dynamics in clinical decision making before treatment in early-stage prostate cancer.
BackgroundBased on a large, representative unscreened cohort from Malmö, Sweden, we have recently reported that a single prostate-specific antigen (PSA) measurement at or before age 50 is a strong predictor of prostate cancer occurring up to 25 years subsequently. We aimed to determine whether this association holds for advanced cancers, defined as clinical stage T3 or higher, or skeletal metastasis at the time of the cancer diagnosis.MethodsIn 1974–1986 blood samples were obtained from a cohort of 21,277 men aged up to 50. Through 1999, 498 men were diagnosed with prostate cancer, and of these 161 had locally advanced or metastatic prostate cancers. Three controls, matched for age and date of venipuncture, were selected for each case. Conditional logistic regression was used to test associations between molecular markers and advanced cancer.ResultsMedian time from venipuncture to diagnosis was 17 years. Levels of all PSA forms and hK2 were associated with case status. Total PSA was a strong and statistically significant predictor of subsequent advanced cancer (area under the curve 0.791; p < 0.0005). Two-thirds of the advanced cancer cases occurred in men with the top 20% of PSA levels (0.9 ng/ml or higher).ConclusionA single PSA test taken at or before age 50 is a very strong predictor of advanced prostate cancer diagnosed up to 25 years later. This suggests the possibility of using an early PSA test to risk-stratify patients so that men at highest risk are the focus of the most intensive screening efforts.
On univariate analysis, two of 12 PSADT and four of 10 PSAV definitions were univariately associated with both BCR and metastasis (P < .05). One PSADT and one PSAV definition had a higher predictive accuracy for BCR over PSA alone, and four PSAV definitions improved prediction of metastasis. However, the improvements in predictive accuracy were small, associated with wide CIs, and markedly reduced if additional predictors of stage and grade were included alongside PSA. Modeling with random variables suggests that similar results would be expected by chance. CONCLUSION We found no clear evidence that any definition of PSA dynamics substantially enhances the predictive accuracy of a single pretreatment PSA alone.
Although PSA velocity is significantly increased in men with prostate cancer up to two decades before diagnosis, it does not aid long-term prediction of prostate cancer.
Objective
To examine our institutional experience in patients treated with partial nephrectomy (PN) for renal cortical tumours (RCTs) of ≥7 cm, as PN is an accepted surgical approach for appropriate RCTs of <7 cm but there are limited data on the use of PN for larger tumours.
Patients and Methods
After Institutional Review Board approval, we examined our prospectively collected surgical database for patients treated with PN for RCTs of ≥7 cm between 1989 and 2008. Pertinent demographic, clinical, surgical and pathological data were reviewed.
Results
In all, 34 patients (37 renal units) were identified for analysis with a median (interquartile range, IQR) age of 63 (52-71) years, median (IQR) tumour size of 7.5 (7.2-9.0) cm with the largest tumour being 19 cm. In 31 renal units (28 patients, 84%) carcinoma was evident, with 16 renal units (43%) having conventional clear cell carcinoma, followed by papillary in eight renal units (21%). Currently, 20 of these 28 patients (71%) are disease free, three are alive with metastatic disease (two had known preoperative metastatic disease), three died from disease and two died from other causes. The median (IQR) preoperative estimated glomerular filtration rate was 65 (55-73) mL/min/1.73 m2, compared with 55 (47-74) mL/min/1.73 m2 after PN (P = 0.003, paired Student's t-test).
Conclusions
Our findings suggest that PN for RCTs of ≥7 cm can be safely performed and provide effective tumour control for selected patients. PN should be considered for patients with appropriate tumours, solitary kidneys or pre-existing renal insufficiency.
Patients with chronic renal failure show a greater incidence of malignancies. We evaluated whether moderately impaired renal function at baseline influenced risk of all cancers during long-term follow in young persons. Our cohort included 33,346 subjects, aged 26–61 years at baseline, in a representative, population-based study enrolling subjects from 1974 to 1992. Median follow-up time was 28 years. Plasma creatinine was analysed as a single measure at baseline. Incident cases of cancer were identified from the Swedish Cancer Registry. We studied 24,552 subjects from the cohort. To account for the unique sampling design, participants were divided by sex and age at baseline into 1,132 older men (age 60), 14,254 younger men (age 40–52), 7,498 older women (age 47–57) and 1,688 younger women (age 35–43). Glomerular filtration rate (GFR) was estimated using the CKD-EPI formula. Patients were classified as having either normal to mildly impaired kidney function (eGFR≥60 mL/min/1.73m2), or moderate kidney dysfunction (eGFR<60 mL/min/1.73m2). We calculated the risk of all cancers using competing risks regression. Overall, 6,595 participants were diagnosed with cancer, and 854 subjects (3.5%) had moderately impaired renal dysfunction at baseline. There was a significant association between moderately decreased GFR and subsequent risk of kidney cancer in younger men (hazard ratio, 3.38; 95% CI, 1.48 to 7.71; P=0.004). However, we found no association with overall long-term cancer risk. Our confirmation of an association between moderately impaired renal function and risk of kidney cancer in younger men requires further exploration of high-risk groups and biological mechanisms.
Summary
The kallikrein, prostate-specific antigen (PSA), is one of the world’s most frequently used disease biomarkers. After almost two decades of research and clinical experience, we are now starting to comprehend its diagnostic and monitoring limitations. Most physicians are aware of PSA’s low cancer-specificity among older men with benign prostatic conditions, but fewer are aware of recent data showing that a prior negative biopsy or a prior PSA below cut-off may have even stronger negative impact. Furthermore, a subtle PSA rise at early middle age strongly correlates to prostate cancer of unquestionable significance. We thoroughly review current and past reports on prostate kallikreins in relation to pathology and epidemiology.
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