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Alexander Haese

Publications and source records attributed to Alexander Haese.

47 records · Page 3Linked to original sources
PubMed2002

International validation of a preoperative nomogram for prostate cancer recurrence after radical prostatectomy.

PURPOSE: We evaluated the predictive accuracy of a recently published preoperative nomogram for prostate cancer that predicts 5-year freedom from recurrence. We applied this nomogram to patients from seven different institutions spanning three continents. METHODS: Clinical data of 6,754 patients were supplied for validation, and 6,232 complete records were used. Nomogram-predicted probabilities of 60-month freedom from recurrence were compared with actual follow-up in two ways. First, areas under the receiver operating characteristic curves (AUCs) were determined for the entire data set according to several variables, including the institution where treatment was delivered. Second, nomogram classification-based risk quadrants were compared with actual Kaplan-Meier plots. RESULTS: The AUC for all institutions combined was 0.75, with individual institution AUCs ranging from 0.67 to 0.83. Nomogram predictions for each risk quadrant were similar to actual freedom from recurrence rates: predicted probabilities of 87% (low-risk group), 64% (intermediate-low-risk group), 39% (intermediate-high-risk group), and 14% (high-risk group) corresponded to actual rates of 86%, 64%, 42%, and 17%, respectively. The use of neoadjuvant therapy, variation in the prostate-specific antigen recurrence definitions between institutions, and minor differences in the way the Gleason grade was reported did not substantially affect the predictive accuracy of the nomogram. CONCLUSION: The nomogram is accurate when applied at international treatment institutions with similar patient selection and management strategies. Despite the potential for heterogeneity in patient selection and management, most predictions demonstrated high concordance with actual observations. Our results demonstrate that accurate predictions may be expected across different patient populations.

Adult↗
PubMed2002

Analysis of clinical stage T2 prostate cancer: do current subclassifications represent an improvement?

PURPOSE: The purpose of this study was to determine whether the extent of palpable cancer within the prostate predicts outcome after radical prostatectomy. PATIENTS AND METHODS: We combined prospectively collected data on 1,755 consecutive clinical stage T2 patients treated with radical prostatectomy alone at four institutions. According to the 1992 American Joint Committee on Cancer tumor-node-metastasis system, 645 (37%) were T2a, 758 (43%) were T2b, and 352 (20%) were T2c. Kaplan-Meier and proportional hazards regression analyses were performed on the 1992 and 1997 T2 subclassifications. After controlling for the effects of prostate-specific antigen (PSA) and biopsy Gleason sum, the two staging systems were compared for their ability to predict recurrence-free survival (RFS). Adjusted RFS curves were constructed using the corrected group prognosis method. RESULTS: Follow-up ranged from 1 to 166 months (median, 26 months). Cancer recurred in 417 (24%) of the T2 patients. The 1992 (P =.005) but not the 1997 (P =.100) T2 subclassification predicted outcome after controlling for PSA and Gleason sum. After covariate adjustment, RFS was 7% higher at 5 years in the 1992 T2a subcategory relative to the T2b subcategory. CONCLUSION: The 1992 American Joint Committee on Cancer system is superior to the 1997 system, and the former adds prognostic information to a model containing pretreatment PSA and Gleason sum. These results suggest that 1992 T2 subclassification derived from palpable findings improves prognostication over the 1997 subclassification.

Humans↗
PubMed2002

Discrimination of benign from malignant prostatic disease by selective measurements of single chain, intact free prostate specific antigen.

PURPOSE: Free prostate specific antigen (PSA) in serum consists of heterogeneous molecular subforms. Recently we developed an immunoassay for selective measurement of a subfraction of free PSA called intact PSA, which has been shown to be closely associated with prostate cancer. We assessed the ability of serum intact PSA to discriminate between benign and malignant prostatic disease. MATERIALS AND METHODS: In serum of 178 men with benign disease and 255 men with prostate cancer we measured total PSA and free PSA using a commercially available immunoassay. Intact PSA levels were analyzed by a newly developed assay specific for noncleaved, that is single chain forms of free PSA. Internally cleaved "nicked" PSA was calculated by subtracting intact from free PSA. We also calculated ratios of intact PSA-to-free PSA (intact-to-free PSA) and nicked PSA-to-total PSA (nicked-to-total PSA). We compared means, medians and ranges of all analytes and ratios in patients with and without cancer for the entire total PSA range and in a subset with total PSA ranging from 2 to 10 ng./ml. Furthermore, various combinations of PSA forms were tested for their predictive ability. For statistical comparison we used the Mann-Whitney U test and ROC analysis. RESULTS: The ratio intact-to-free PSA was significantly higher in cancer (median 48.5%) compared to noncancer cases (median 41.8%, p <0.0001). Conversely, the ratio nicked-to-total PSA was significantly higher in men without compared to those with prostate cancer (median 11.0% and 6.0%, respectively, p <0.0001). Highest discriminative ability was observed for a combination of intact, total and free PSA (log [intact, free, total], AUC = 0.773) followed by nicked-to-total PSA (AUC 0.755). In the subgroup of patients with total PSA levels from 2 to 10 ng./ml. only the AUC of log intact, free, total (AUC 0.706, p = 0.0017) and nicked-to-total PSA (AUC 0.704,p = 0.0019) were significantly larger compared to the AUC of total PSA (AUC 0.602). CONCLUSIONS: By contrast to measuring crude free PSA concentration, selective determination of specific free PSA subforms, intact PSA and nicked PSA proved to be useful to discriminate men with benign from malignant prostatic disease. These markers may serve to generate specific serum profiles of PSA for improved specificity and early detection of prostate cancer. To translate the encouraging statistical advantage shown in this study into a clinically applicable tool warrants further investigation.

Biomarkers, Tumor↗
PubMed2002

Prediction of tumor heterogeneity in localized prostate cancer.

Clinical T1 and T2 prostatic carcinoma is a heterogeneous tumor with respect to pathologic stage and outcome. In the authors' experience, 60% of patients have a pT2 prostatic carcinoma, and 2% to 4% have tumors less than 0.5 cm3 in volume. The latter group cannot be predicted by the use of preoperative parameters with a sufficient sensitivity and specificity. Quantitative analysis of six systematic biopsies, that is, reporting the number of biopsies with any Gleason grade 4 or 5 cancer or the number of biopsies with more than 50% Gleason grade 4 and 5 cancer, together with preoperative PSA levels can be used to predict the different pathologic stages and risk groups of patients with T1 or T2 prostatic carcinoma. CART analysis that using these preoperative parameters can predict the lymph node stage and the capsular penetration on each side of the prostate with a sufficient positive and negative predictive value and a sufficient specificity to avoid routine lymphadenectomy in approximately 80% of the patients classified as a low-risk group for having lymph nodes positive for disease. CART analysis also allows a solid identification of patients in whom the unilateral or bilateral nerve may be spared during surgery. These algorithms may be improved further by determining the HK-2 level in the blood or by including other molecular biologic markers in the analysis of the biopsies. Clinical T1 or T2 prostatic carcinoma is a heterogeneous but fairly predictable tumor.

Biopsy↗
PubMed2002

Assessment of clinical and pathologic characteristics predisposing to disease recurrence following radical prostatectomy in men with pathologically organ-confined prostate cancer.

OBJECTIVE: To identify risk factors for biochemical failure after radical prostatectomy (RP) in men with pathologically organ-confined (OC) prostate cancer (PCa). METHODS: Clinical and pathological characteristics of 331 consecutive men with pT2N0 PCa treated solely with RP were used in Cox proportional hazard models to identify independent predictors of prostate specific antigen (PSA) failure (PSA > or = 0.1 ng/ml). All pathologic specimens were step sectioned at 3 mm. RESULTS: Twelve patients (3.6%) failed at a median follow-up of 26 months (range 0.2-99.6 months) and 120 men remained at risk 3 years after RP. In univariate Cox models PSA (P < 0.001), percentage of high-grade cancer (P < 0.001) total and high-grade cancer volume (P = 0.001 and P < 0.0001, respectively) and RP Gleason sum (P = 0.003) represented significant predictors of PSA failure. Clinical stage (P = 0.4), surgical margin status (P = 0.3), age (P = 0.2), and pathologic evidence of unilateral versus bilateral PCa (P = 0.6) failed to reveal significance. In receiver operator curve (ROC) analyses, high-grade cancer volume achieved highest outcome predictive accuracy (area under the curve (AUC 0.93)), which was not exceeded by Cox regression-based nomogram combining serum PSA, RP Gleason sum, margin status and pathologic evidence of unilateral versus bilateral PCa (AUC 091). Predictive accuracy of this multivariate nomogram was not enhanced by adding total cancer volume (AUC 0.93), high-grade cancer volume (AUC 0.90), or percentage of high-grade cancer (AUC 0.90). CONCLUSIONS: In pT2N0 PCa high-grade cancer volume appears to represent the most important pathologic factor for prediction of outcome following RP. However, similar predictive accuracy may be achieved by combining routinely available tumor characteristics.

Area Under Curve↗
PubMed2002

Patient-reported sexual function after nerve-sparing radical retropubic prostatectomy.

OBJECTIVE: Improved selection criteria have lead to an increasing number of nerve-sparing radical retropubic prostatectomies (RRP) in patients with clinically localised prostate cancer (PCA). Patient questionnaire based outcome analysis on post-operative erectile function after uni- or bilateral nerve-sparing RRP is described. METHODS: Between January 1992 and March 1999, 366 patients (mean age 62.5 years) underwent uni- or bilateral nerve-sparing RRP at our institution. Indication for nerve-sparing procedure was based on the results of a multivariate classification and regression tree analysis (CART). For evaluation of post-operative patient-reported rates of sexual and erectile function non-validated and validated questionnaires (IIEF 5) were administered after a follow-up of 12 months. Data of five operation periods were analysed. RESULTS: The unilateral procedure resulted in rates of 13-29% of erections sufficient for unassisted intercourse. Some degree of tumescence was reported by 37-73% of the remaining patients. Bilateral nerve-sparing procedures were almost exclusively performed in periods 3-5, only four patients of period 2 received the bilateral procedure. Here, rates of erections sufficient for intercourse were 25% (period 2), 61% (period 3), 50% (period 4), and 52% (period 5), respectively. Patients with grades 4 and 5 erections had IIEF scores of 19.2 and 20.2 and patients without rigidity or tumescence had scores of 5.7 and 7.0 after uni- and bilateral nerve-sparing procedure, respectively. Patients <60 years of age had better erections than those > or =60 (unilateral: 19% versus 13%, bilateral 45% versus 38%). CONCLUSION: Compared to a unilateral nerve-sparing procedure, the bilateral nerve-sparing technique revealed much better results inasmuch as about 50% of the patients reported recovery of erections sufficient for sexual intercourse without use of sexual aids.

Adult↗
PubMed2002

Percent free prostate specific antigen is not an independent predictor of organ confinement or prostate specific antigen recurrence in unscreened patients with localized prostate cancer treated with radical prostatectomy.

PURPOSE: We studied the controversial relationship of percent free prostate specific antigen (PSA) with organ confined prostate cancer and PSA failure after radical prostatectomy. MATERIALS AND METHODS: We tested the characteristics of the percent free PSA monoclonal Immulite DPC Immunoassay (Diagnostic Products Corp., Los Angeles, California) for predicting organ confinement in 698 consecutive unscreened men treated only with radical prostatectomy between 1995 and 2000. In addition, we assessed the ability of percent free PSA to predict post-radical prostatectomy PSA failure, defined as PSA 0.1 ng./ml. or greater, in a subset of 581 men in whom followup was available. All statistical analyses were repeated for stage T1c cancer with PSA between 2 and 10 ng./ml. RESULTS: On univariate analyses percent free PSA achieved significance for predicting organ confined disease at all clinical stages (p <0.001) and for stage T1c cancer with PSA between 2 and 10 ng./ml. (p = 0.012). However, significance dissipated after controlling for total PSA, biopsy Gleason sum and clinical stage (p = 0.135 and 0.851, respectively). In univariate Cox models percent free PSA failed to predict PSA failure across stages (p = 0.341), as well as in stage T1c cancer (p = 0.93). In multivariate analyses controlling for traditional PSA biopsy grade and clinical stage (p <0.001), percent free PSA failed to contribute to predicting PSA failure (p = 0.342). In the stage T1c subset biopsy Gleason sum (p <0.001) and PSA (p = 0.018) remained significant, in contrast to percent free PSA (p = 0.237). CONCLUSIONS: Percent free PSA has no independent, statistically significant association with organ confined status or posttreatment PSA outcome in unscreened patients who undergo radical prostatectomy for localized prostate cancer.

Humans↗
PubMed2002

Percent free prostate specific antigen in the total prostate specific antigen 2 to 4 ng./ml. range does not substantially increase the number of biopsies needed to detect clinically significant prostate cancer compared to the 4 to 10 ng./ml. range.

PURPOSE: Percent free prostate specific antigen (PSA) is useful to select patients for prostate biopsy with total PSA 4 to 10 ng./ml. However, 20% of men with PSA between 2.6 and 4 ng./ml. harbor significant prostate cancer and percent free PSA has been suggested to aid in the decision to biopsy in this total PSA range as well. Concerns exist that the number of biopsies needed to detect 1 cancer in this range may be inappropriately high. In a prospective referral population we evaluated sensitivity and specificity of various percent free PSA cutoffs and determined the biopsy-per-cancer ratio in the PSA 2 to 4 ng./ml. range in men with a benign digital rectal examination, and report on the biological nature of the detected cancers based on Gleason score. Results were compared to those obtained from a reference group of patients (PSA 4 to 10 ng./ml., benign digital rectal examination) from the same prospective referral cohort. MATERIALS AND METHODS: Total PSA and free PSA were measured and percent free PSA was calculated. Of the initial 1,602 men 756 had a benign digital rectal examination and PSA 4 to 10 ng./ml., and 219 had a benign digital rectal examination and PSA 2 to 4 ng./ml. Sensitivity, specificity, the number of true positive (evidence of cancer) and false-positive (no evidence of cancer) biopsies were determined. The ratio of true positive biopsies-to-all biopsies performed was used to determine the biopsy-per-cancer ratio. Gleason score of the detected cancers was evaluated. The procedure was repeated for the PSA 4 to 10 ng./ml. range. RESULTS: In the PSA 4 to 10 ng./ml. range a sensitivity of 63.7% to 92.5% with a specificity of 57.5% to 18.7% was found when percent free PSA was 18% to 25%. On average 3 biopsies were needed to detect 1 cancer. When PSA was 2 to 4 ng./ml. sensitivity was 46.3% to 75.6% and specificity was 73.6% to 37.6% when the same percent free PSA cutoff was examined. Calculation of the biopsy-per-cancer ratio for various percent free PSA cutoffs revealed that 3 to 5 biopsies were needed to find 1 cancer. Of 41 cancers detected in the PSA 2 to 4 ng./ml. range 6 had a Gleason score 5. The majority (28 of 41) of cases had a Gleason score of 6. Gleason score was 7 in 5 patients and 8 in 1. CONCLUSIONS: In the PSA 4 to 10 ng./ml. range high sensitivity for prostate cancer detection is critical and 3 biopsies are needed to detect 1 cancer. In the PSA 2 to 4 ng./ml. range a percent free PSA cutoff of 18% to 20% detected about 50% of cancers while sparing up to 73% of unnecessary biopsies with a biopsy-to-cancer ratio of 3 to 4:1. Percent free PSA can be applied to the PSA 2 to 4 ng./ml. range to detect prostate cancer and only moderately increases the number of biopsies needed to detect 1 significant cancer compared to the greater than 4 to 10 ng./ml. range.

Aged↗
PubMed2001

New serum tests for the diagnosis of prostate cancer.

Prostate-specific antigen (PSA) has had a profound impact on the early diagnosis, treatment and follow-up of prostate cancer, the most common malignancy in men. However, it is not only a marker for prostate cancer but is also often expressed in benign conditions such as benign prostatic hyperplasia, prostatitis and other inflammatory disorders. For early detection of prostate cancer, limitations of the use of PSA become obvious; its widespread use has led to extensive expensive and often unnecessary diagnostic procedures associated with significant morbidity. New serum tests derived from total PSA may play a key role in enhancing the accuracy of prostate cancer diagnosis. The ratio of free to total PSA improves specificity while maintaining a high sensitivity for prostate cancer detection for men with a total PSA of 2.5-10 ng/ml who also have a normal digital rectal examination. Human glandular kallikrein 2 also has the potential to be a valuable tool in combination with both total and free PSA for the early diagnosis of prostate cancer. However, the optimal clinical use of human glandular kallikrein 2 still remains to be clarified. Complex PSA seems to be a reliable tool and equivalent alternative to total PSA to improve specificity at high sensitivity levels in men with suspected prostate cancer, mainly for PSA levels below 4 ng/ml. Several newly discovered isoforms of free PSA (bPSA, [-2]pPSA and inactive intact PSA) may also impact the early detection of prostate cancer, with encouraging preliminary results that warrant further clinical investigation. (c) 2001 Prous Science. All rights reserved.

Journal Article↗
PubMedDate not supplied

A validation of two preoperative nomograms predicting recurrence following radical prostatectomy in a cohort of European men.

Kattan et al. at Baylor College of Medicine and D'Amico et al. at Harvard Medical School have each developed preoperative nomograms for prostate cancer recurrence after radical prostatectomy based on readily available clinical variables. Calibration and validation of those tools was achieved using North American patient cohorts, and their validity has not yet been shown in patients from other continents. We investigated the predictive accuracy of these nomograms when applied to European men with localized prostate cancer. Clinical data from patients who underwent radical prostatectomy at the University-Hospital Hamburg and fitted the respective derivation criteria were used for external validation (n = 1003 for the Kattan-Nomogram, n = 932 men for the D'Amico-Nomogram). Nomogram predictions of the probability for 2-years and 5-years freedom from recurrence predicted by the D'Amico-Nomogram and the Kattan-Nomogram respectively were compared with actual follow-up. The predictive accuracy of the nomograms was tested using areas under the receiver-operating-characteristic curves (AUC). The D'Amico-Nomogram AUC predicting 2-years probability of freedom from PSA recurrence was 0.80 vs. Kattan-Nomogram 5-years prediction with an AUC of 0.83. Using the 932 patients who exactly fit the derivation criteria of both nomograms, the predictive accuracy of the Kattan-Nomogram was 0.81. The superiority in predictive accuracy of the Kattan-Nomogram was statistically significant (p = 0.0274) but of unclear clinical significance. The two nomograms predicted recurrence with similar accuracy when applied to men diagnosed with localized prostate cancer in Germany. The high predictive accuracy of both nomograms demonstrates that these predictive tools derived in the U.S. can be applied to non-U.S. patients.

Cohort Studies↗