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Markus Graefen

Publications and source records attributed to Markus Graefen.

At least 37 records · Page 2Linked to original sources
PubMed2006

Validation of a nomogram for prediction of side specific extracapsular extension at radical prostatectomy.

PURPOSE: We have previously have reported a tree structured regression model for predicting SS-ECE. Others recently reported a logistic regression based SS-ECE nomogram. We developed a nomogram and compared the performance and discriminant properties of the tree regression and the nomogram in a contemporary cohort of European patients treated with radical retropubic prostatectomy. MATERIALS AND METHODS: The cohort consisted of 1,118 patients with pretreatment prostate specific antigen 0.1 to 73.2 ng/ml (median 6.6). Each of the 2,236 prostate lobes was considered separately. Clinical stage, pretreatment PSA, biopsy Gleason sum, percent positive cores and percent cancer in the biopsy specimen were used as predictors in a logistic regression model predicting SS-ECE. Regression coefficients were then used to generate an SS-ECE nomogram. Performance characteristics and discriminant properties of the previously published tree regression were also tested in the same cohort. For internal validation and to decrease overfit bias 200 bootstrap re-samples were applied to accuracy estimates for each method. RESULTS: ECE was present in 303 of 1,118 radical retropubic prostatectomy specimens (27%) and in 385 lobes (17%). In logistic regression models all variables were statistically significant multivariate predictors of SS-ECE except the percent of positive biopsy cores (p = 0.7). Bootstrap corrected predictive accuracy of the SS-ECE nomogram was 0.840 vs 0.700 for the tree regression model. CONCLUSIONS: Logistic regression based nomogram predictions of SS-ECE are highly accurate and represent a valuable aid for assessing the risk of ECE prior to surgery.

Calibration↗
PubMed2006

Prediction of postoperative sexual function after nerve sparing radical retropubic prostatectomy.

PURPOSE: Preservation of sexual function is one of the main objectives in radical prostatectomy. We assessed possible predictive factors for postoperative sexual function including preoperative International Index of Erectile Function score, age and extent of nerve sparing procedures for more precise preoperative counseling of patients undergoing radical prostatectomy. MATERIALS AND METHODS: Between January 2000 and December 2001 a total of 694 patients with clinically organ confined prostate cancer underwent nerve sparing radical prostatectomy. Preoperative erectile function was assessed with the International Index of Erectile Function score. After at least 12 months of followup patients were asked to answer the International Index of Erectile Function and Quality of Life Questionnaire C 30 via mail. RESULTS: A total of 411 patients responded to the questionnaire, 122 of whom underwent unilateral nerve sparing radical prostatectomy and 289 underwent bilateral nerve sparing radical prostatectomy. Data on preoperative and postoperative International Index of Erectile Function scores were available for 389 patients. Data on the International Index of Erectile Function and the postoperative Quality of Life Questionnaire C 30 were available for 382 patients. The median decrease in International Index of Erectile Function score was 7 points. Patients undergoing unilateral nerve sparing radical prostatectomy had a significantly stronger decrease in International Index of Erectile Function score compared to patients undergoing the bilateral nerve sparing procedure (12 vs 6 points). Preoperative International Index of Erectile Function score and extent of nerve sparing (unilateral vs bilateral nerve sparing radical prostatectomy) were significantly associated with better postoperative sexual function whereas age was not. Based on preoperative International Index of Erectile Function score, surgical technique and age, the likelihood of postoperative satisfactory erectile function can be defined preoperatively. CONCLUSIONS: We confirmed the impact of the extent of nerve sparing (unilateral vs bilateral nerve sparing radical prostatectomy) and highlighted the effect of preoperative erectile function as measured by the International Index of Erectile Function and age at surgery on postoperative sexual function. Our data can be used for counseling patients undergoing radical nerve sparing prostatectomy regarding recovery of erectile function.

Coitus↗
PubMed2006

Significant upgrading affects a third of men diagnosed with prostate cancer: predictive nomogram and internal validation.

OBJECTIVE: To explore the rate of significant upgrading from biopsy to radical prostatectomy (RP) specimens in a contemporary cohort, and to develop a prognostic model capable of predicting the probability of significant upgrading, as previous reports indicate that up to 43% of men with low-grade prostate cancer at biopsy will be diagnosed with high-grade cancer at RP. PATIENTS AND METHODS: The study cohort comprised 4789 men (median age 63 years, range 39-82) treated with RP, with available clinical stage, prostate-specific antigen levels, biopsy and RP Gleason sum values. These variables were used as predictors in multivariate logistic regression models (LRMs) addressing the rate of significant Gleason sum upgrading, defined as a Gleason sum increase either from < or = 6 to > or = 7 or from 7 to > or = 8 between the biopsy and RP specimens. Regression coefficients were used to develop and validate (200 bootstrap re-samples) a nomogram predicting significant biopsy Gleason sum upgrading. RESULTS: Significant biopsy Gleason sum upgrading was recorded in 1349 (28.2%) patients. In multivariate LRMs, all predictors were highly significant (all P < 0.001). The bootstrap-corrected accuracy of the nomogram predicting the probability of significant Gleason sum upgrading between biopsy and RP specimens was 75.7%. CONCLUSION: Our nomogram might prove highly useful when the possibility of a more aggressive Gleason variant could change the treatment options.

Adult↗
PubMed2006

Circulating tumour-associated plasma DNA represents an independent and informative predictor of prostate cancer.

OBJECTIVE: To investigate whether preoperative plasma levels of free DNA can discriminate between men with localized prostate cancer and benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: In all, 161 referred patients suspicious for prostate cancer either by an elevated prostate-specific antigen (PSA) level and/or abnormal digital rectal examination (DRE) were included in this prospective study. Peripheral plasma was taken before prostate biopsy and genomic DNA was extracted from the plasma using the a commercial kit and a vacuum chamber. After controlling for age, PSA level, the percentage free/total (f/t) PSA and prostate volume, the median prostate cancer plasma DNA concentration served as diagnostic threshold in uni- and multivariate logistic regression models. Multivariate models were subjected to 200 bootstraps for internal validation and to reduce over-fit bias. RESULTS: Subgroups consisted of 142 men with clinically localized prostate cancer and 19 with BPH. The median plasma concentration of cell-free DNA was 267 ng/mL in men with BPH vs 709 ng/mL in men with prostate cancer. In univariate analyses, plasma DNA concentration was a statistically significant and informative predictor (P = 0.032 and predictive accuracy 0.643). In multivariate analyses, it remained statistically significant after controlling for age, tPSA, f/tPSA and prostate volume, increasing the predictive accuracy by 5.6%. CONCLUSIONS: Our data suggest that plasma DNA level is a highly accurate and informative predictor in uni- and multivariate models for the presence of prostate cancer on needle biopsy. The predictive accuracy was substantially increased by adding plasma DNA level. However, larger-scale studies are needed to further confirm its clinical impact on prostate cancer detection.

Adult↗
PubMed2006

Prostate cancer nomograms are superior to neural networks.

INTRODUCTION: Several nomograms have been developed to predict PCa related outcomes. Neural networks represent an alternative. METHODS: We provide a descriptive and an analytic comparison of nomograms and neural networks, with focus on PCa detection. RESULTS: Our results indicate that nomograms have several advantages that distinguish them from neural networks. These are both quantitative and qualitative. CONCLUSION: In the field of PCa detection, nomograms appear to outweigh the benefits of neural networks. However, the neural network methodology represents a valid alternative, which should not be underestimated.

Forecasting↗
PubMed2005

Development and internal validation of a nomogram predicting the probability of prostate cancer Gleason sum upgrading between biopsy and radical prostatectomy pathology.

OBJECTIVE: Previous reports indicate that as many as 43% of men with low grade PCa at biopsy will be diagnosed with high-grade PCa at RP. We explored the rate of upgrading from biopsy to RP specimen in our contemporary cohort, and developed a model capable of predicting the probability of biopsy Gleason sum upgrading. MATERIALS AND METHODS: The study cohort consisted of 2982 men treated with RP, with available clinical stage, serum prostate specific antigen and biopsy Gleason scores. These clinical data were used as predictors in multivariate logistic regression models (LRM) addressing the rate of Gleason sum upgrading between biopsy and RP pathology. LRM regression coefficients were used to develop a nomogram predicting the probability of Gleason sum upgrading and was subjected to 200 bootstrap resamples for internal validation and to reduce overfit bias. RESULTS: Overall, 875 patients were upgraded (29.3%). In multivariate LRMs, all predictors were highly significant (all p values <0.0001). Bootstrap-corrected predictive accuracy of the nomogram predicting the probability of Gleason sum upgrading between biopsy and RP was 0.804. CONCLUSION: We developed a highly accurate clinical aid for treatment decision-making. It may prove useful when the possibility of a more aggressive Gleason variant may change the treatment options.

Biopsy↗
PubMed2005

Open retropubic nerve-sparing radical prostatectomy.

Retropubic radical prostatectomy is the most commonly used therapeutic option for the treatment of clinically localized prostate cancer. An ongoing stage migration toward organ-confined cancers allows performance of a nerve-sparing procedure in a growing number of patients. Key elements for achieving convincing functional results are a sphincter-preserving ligation of the distal part of the Santorini plexus and the subtle preparation of the neurovascular bundle. This article gives a detailed description of the operative technique, which is demonstrated in the attached DVD. Furthermore, indication, oncologic outcome, and functional results addressing postoperative urinary continence and potency are discussed.

Humans↗
PubMed2005

Association of free-prostate specific antigen subfractions and human glandular kallikrein 2 with volume of benign and malignant prostatic tissue.

BACKGROUND: We investigated the association of different subfractions of prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2), such as total PSA (tPSA), complexed PSA (cPSA), free PSA (fPSA), "single-chain Intact fPSA" (fPSA-I), "multi-chain nicked fPSA" (fPSA-N), and total hK2 with volumes of total prostate gland, transition zone (tz), and prostate cancer (PCa) tissue in patients with benign and malignant prostatic disease. METHODS: Serum samples were collected from men with negative biopsy (n=164) and PCa (n=252). Total and fPSA were measured using a commercially immunoassay. We measured hK2 and fPSA-I by previously reported in-house research assays specific for hK2 and single-chain, non-cleaved fPSA, respectively. Levels of fPSA-N (=fPSA-fPSA-I) and cPSA (=tPSA-fPSA) were calculated. Total prostate and tz volume were measured using transrectal ultrasound (TRUS); PCa volume was calculated using a computer assisted volumetric program. Association with tz and cancer volumes (CaVols) was performed by linear regression analysis. RESULTS: All PSA subfractions and hK2 were associated with tz volume in multivariable linear regression analysis. Only hK2, fPSA, and fPSA-N were significantly associated with CaVol in multivariable analysis, fPSA-I seemed to be cancer related. CONCLUSIONS: The multi-chain fPSA-N subfractions of fPSA may be a valuable predictor of both benign prostate hyperplasia (BPH) and CaVol that is likely to be more useful in predicting tz volumes than CaVols. fPSA-I may provide information on cancer without being influenced by the presence of BPH.

Aged↗
PubMed2005

Reasonable delay of surgical treatment in men with localized prostate cancer--impact on prognosis?

PURPOSE: In many centers patients with clinically localized prostate cancer might be confronted with a delay in therapy due to not immediately available treatment capacity at that specific center. Furthermore, a growing amount of patients want to have a second or third opinion before they finally decide what therapeutic option to choose. We investigated whether a reasonable delay from diagnosis to definitive treatment impact recurrence free survival rates in men undergoing radical prostatectomy (RP) for localized prostate cancer. MATERIAL AND METHODS: Preoperative data of 795 men treated for localized prostate cancer by RP between 1/1992 and 6/2000 were evaluated including pretreatment PSA, clinical stage and biopsy Gleason score. In addition, time from biopsy to the date of RP was obtained and investigated as a potential prognostic factor. The influence of the time gap between biopsy and surgery was statistically evaluated by univariate Cox regression analyses and Kaplan-Meier analyses; a multivariate Cox Modell was performed including all preoperative parameters. Relapse following RP was defined as a postoperative PSA level >0.1 ng/ml. RESULTS: Mean followup of the patients was 33 months (1-116 months). Twenty-five percent of the patients failed during that time period. Mean time gap between diagnosis and treatment was 62 days (median 54 days) ranging from 5 to 518 days. Univariate Cox regression analysis showed no significant correlation (p=0.062) of waiting time with recurrence rate. Multivariate Cox regression documented a highly significant association of PSA (p<0.001), clinical stage (p=0.001) and biopsy Gleason grade (p<0.001) but not not for time to treatment (p=0.841). In patients with high-grade cancer again no significant impact of treatment delay was found. CONCLUSION: Treatment delay in the investigated time span of a few months did not adversely affect recurrence free survival rates. Patients can be reassured that they can evaluate treatment options without compromising efficacy due to a delay in treatment.

Biopsy↗
PubMed2005

Surgical management of prostate cancer: advances based on a rational approach to the data.

The management of localised prostate cancer has undergone important changes in the past two decades, with major improvements in surgical technique, a greater emphasis on structured assessment of quality of life, and a greater attempt to tailor treatment to biological risk. Disease diagnosis is predicated on identification of demographic risk factors, serum levels of prostate-specific antigen and its derivatives, and extended biopsy techniques. Surgical removal of the prostate may be accomplished by open or minimally invasive techniques and in experienced hands results in good functional outcomes a high rate of cure for those with organ confined disease. Radical prostatectomy is also appropriate in selected patients with locally advanced disease and after failed radiation therapy.

Biopsy↗
PubMed2005

Influence of nerve-sparing (NS) procedure during radical prostatectomy (RP) on margin status and biochemical failure.

PURPOSE: To evaluate whether nerve-sparing procedure itself is a risk factor for biochemical recurrence in carefully selected patients. MATERIAL AND METHODS: We compared patients of our historical series who in retrospect were candidates for nerve-sparing (NS) procedure with a contemporary cohort of patients. With respect to stage migration and selection bias between these two groups we performed a multivariate analysis adjusting for all explanatory variables in the model. NS was performed in n = 723 patients (bilateral n = 359, unilateral n = 364) in comparison to n = 620 patients undergoing non-NS RP, comprising n = 756 patients within the favorable pT2 category. We examined the association of clinical and histopathological parameters in relation to PSA recurrence in uni- and multivariate analyses including NS as a variable. Furthermore, for each prostate lobe separately we determined whether surgical procedure (nerve-sparing vs. non-nerve-sparing RP) resulted in a positive margin. RESULTS: In univariate analysis there was no difference in pT2 (log rank p = 0.091), pT3a (log rank p = 0.171) and pT3b (log rank p = 0.110) cancers between patients treated with NS compared to non-NS surgery. The 3- and 5-year recurrence free survival rate for patients with pT2, pT3a and pT3b cancers treated by NS vs. non-NS were 96.3/94.9 vs. 94.9/90.8, 75.0/61.8 vs. 73.4/55.0 and 46/30 vs. 38/23. Multivariate regression analysis showed no association with PSA failure (p = 0.798) for patients who underwent NS. Capsular penetration (p < 0.001), lymph-node status (p < 0.001), seminal vesicle invasion (p < 0.001), surgical margin status (p = 0.0130), Gleason score (p < 0.001) and preoperative PSA (p = 0.005) were significantly associated with risk of failure. The positive margin rate per each prostate lobe in pT2 cancers was 6.5% vs. 5.1% in NS and non-NS cases, 10.3% vs. 17.3% in patients with extracapsular extension and 15.0% vs. 25.1% in cases with seminal vesicle invasion respectively. CONCLUSION: NS RP is an oncologically safe procedure provided that appropriate preoperative selection of patients by means of a validated nomogram is performed. Moreover, evaluation of positive margins in patients undergoing NS and non-NS RP revealed no evidence that adequacy of tumor excision is compromised by NS procedure.

Aged↗
PubMed2005

Prognostic impact of positive surgical margins in surgically treated prostate cancer: multi-institutional assessment of 5831 patients.

OBJECTIVES: To assess the prognostic significance of a positive surgical margin in the radical prostatectomy specimen, and to test for the presence of statistically significant interactions between surgical margin status and select pathologic stage variables. METHODS: We combined prospectively collected data from 7816 consecutive patients treated with radical prostatectomy at eight institutions. The pretreatment serum prostate-specific antigen level, pathologic Gleason sum, surgical margin status (positive versus negative), presence of extracapsular extension, seminal vesicle involvement, and pelvic lymph node status were examined as predictors of the rate of biochemical progression in 5831 patients with complete records. RESULTS: In multivariate Cox regression models, a positive surgical margin was associated with a 3.7-fold greater risk of progression (P = 0.001). Moreover, a statistically significant interaction was found between surgical margin status and Gleason sum 7 to 10 (P = 0.008) and lymph node invasion (P < 0.001). CONCLUSIONS: The presence of a positive surgical margin in the radical prostatectomy specimen has an adverse effect on prognosis. The greatest risk of biochemical recurrence may be expected if a positive surgical margin is present with Gleason sum 7 to 10 disease or lymph node invasion.

Disease-Free Survival↗
PubMed2005

Development and validation of a nomogram predicting the outcome of prostate biopsy based on patient age, digital rectal examination and serum prostate specific antigen.

PURPOSE: We developed and validated a nomogram which predicts presence of prostate cancer (PCa) on needle biopsy. MATERIALS AND METHODS: We used 3 cohorts of men who were evaluated with sextant biopsy of the prostate and whose presenting prostate specific antigen (PSA) was not greater than 50 ng/ml. Data from 4,193 men from Montreal, Canada were used to develop a nomogram based on age, digital rectal examination (DRE) and serum PSA. External validation was performed on 1,762 men from Hamburg, Germany. Data from these men were subsequently used to develop a second nomogram in which percent free PSA (%fPSA) was added as a predictor. External validation was performed using 514 men from Montreal. Both nomograms were based on multivariate logistic regression models. Predictive accuracy was evaluated with areas under the receiver operating characteristic curve and graphically with loess smoothing plots. RESULTS: PCa was detected in 1,477 (35.2%) men from Montreal, 739 (41.9%) men from Hamburg and 189 (36.8%) men from Montreal. In all models all predictors were significant at 0.05. Using age, DRE and PSA external validation AUC was 0.69. Using age, DRE, PSA and %fPSA external validation AUC was 0.77. CONCLUSIONS: A nomogram based on age, DRE, PSA and %fPSA can highly accurately predict the outcome of prostate biopsy in men at risk for PCa.

Adolescent↗
PubMed2005

A multicenter clinical trial on the use of (-5, -7) pro prostate specific antigen.

PURPOSE: The determination of pro prostate specific antigen (proPSA) forms has been suggested to be promising in prostate cancer diagnosis. In this multicenter trial we evaluated the diagnostic usefulness of (-5, -7) proPSA. MATERIALS AND METHODS: A total of 2,055 white men, including 1,046 with and 1,009 without prostate cancer, with total PSA (tPSA) between 0.28 and 81 ng/ml were retrospectively analyzed. Of these men 2,026 and 1,727 had tPSA less than 20 and less than 10 ng/ml, respectively. All subjects were untreated for prostatic disease and underwent multisector needle biopsy of the prostate. An Elecsys 2010 analyzer was used to determine tPSA, free PSA (fPSA) and (-5, -7) proPSA in the 2,055 serum samples. ROC analyses were performed to discriminate men with biopsy positive and negative results in the entire and in select tPSA ranges. RESULTS: In the select tPSA range 2 to 4 ng/ml the area under the ROC curve for proPSA (0.53) and proPSA/fPSA (0.59) was not significantly larger than that for tPSA (0.60) or the fPSA/tPSA (f/tPSA) ratio (0.64). In the tPSA range 4 to 10 ng/ml the area under the curve for the ratio proPSA/fPSA (0.67) was larger than for tPSA (0.53) but not larger than for f/tPSA (0.69). The f/tPSA ratio demonstrated the best discriminatory power in this tPSA range of 4 to 10 ng/ml. CONCLUSIONS: In this multicenter study no improvement in diagnostic accuracy was shown when comparing (-5, -7) proPSA and the corresponding ratios with tPSA or f/tPSA. Further studies using other proPSA forms or tumor associated proteins should be done.

Adult↗
PubMed2005

Extraction and processing of high quality RNA from impalpable and macroscopically invisible prostate cancer for microarray gene expression analysis.

Molecular analyses of early-stage prostate cancers are necessary to assess their potential clinical significance based on established and/or novel biomarkers for tailored clinical management. A prerequisite for the application of RNA-based analyses of such, mostly macroscopically-undetectable, small prostate carcinomas is the recovery and preservation of sufficient RNA quantities and quality. Furthermore, in prostate cancer, heterogeneity is a common phenomenon that includes a juxtaposition of different tissue compositions and variable histological grades within the same tumor focus. To better understand the molecular mechanisms of prostate cancer, it is essential to correlate molecular data with a specific cell type. Here, we present a tissue collecting protocol which is aligned with the preoperative evaluation of tumor localization. In combination with the technique of laser microdissection and pressure catapulting, we are able to preserve RNA of high quality from homogeneous cell populations of macroscopically-undetectable small prostate carcinomas. To obtain the necessary RNA quantities for whole genome cDNA microarrays, the isolated total RNAs were amplified by T7-based RNA-polymerase in vitro transcription. The microarray analyses (Human Unigene Set RZPD3.1) resulted in 216 differentially expressed genes (191 down-regulated, 25 up-regulated). Among these were several known prostate cancer relevant genes, such as AMACR, TARP, LIM, GPR160 (all up-regulated), CAV1, NTN1, MT1X; CLU, TRIM29, SPARCL1 and HSPB8 (all down-regulated).

Down-Regulation↗
PubMed2004

Prostate-specific antigen and related isoforms in the diagnosis and management of prostate cancer.

Despite its unparalleled merits for prostate cancer detection and staging, prostate-specific antigen (PSA) is not a marker for prostate cancer only, but also is expressed in benign conditions. For early detection, limitations of PSA are obvious. Its widespread use has led to an extensive amount of expensive and often unnecessary diagnostic procedures associated with significant morbidity. Total PSA derivatives may enhance 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 to 10 ng/mL. Human glandular kallikrein also has the potential to be a valuable tool in combination with total and free PSA for early diagnosis of prostate cancer. Complex PSA seems to be a reliable tool to improve specificity at high sensitivity levels in men with suspected prostate cancer (mainly in PSA levels below 4 ng/mL). Newly discovered isoforms of free PSA also may impact early detection of prostate cancer with encouraging preliminary results that warrant further clinical investigation.

Humans↗
PubMed2004

Assessment of the enhancement in predictive accuracy provided by systematic biopsy in predicting outcome for clinically localized prostate cancer.

PURPOSE: Current localized prostate cancer treatment outcome nomograms rely on prostate specific antigen (PSA), tumor stage and grade. We investigated whether the addition of prostate biopsy features may enhance the accuracy of a nomogram predicting recurrence after radical prostatectomy (RP). MATERIALS AND METHODS: Clinical data from 1,152 patients who underwent RP were used and included PSA, clinical stage, biopsy Gleason grade and systematic biopsy information that quantified the amount of cancer and high grade cancer. Predictive accuracy for freedom from recurrence after RP was assessed with and without tumor quantification in the biopsy by the area under the receiver operating characteristics curve (AUC). RESULTS: Percentage and number of cores with cancer, and percentage and number of cores with high grade cancer were predictors of outcome when added to models that included PSA, Gleason grade and clinical stage (all p <0.0001). Nomogram accuracy with 3 traditional variables (AUC 0.790) was minimally enhanced with the addition of percentage or number of positive cores (AUC 0.804 and 0.800, respectively), or percentage or number of cores with high grade cancer (AUC 0.802 and 0.800, respectively). Maximum predictive accuracy of 0.811 was achieved after supplementing the traditional 3-variable nomogram with various combinations of additional pathological predictors. CONCLUSIONS: The information provided by systematic biopsies substantially improves the ability to predict outcome following RP. However, some incremental predictive accuracy was achieved by adding systematic biopsy features.

Adult↗