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Markus Graefen

Publications and source records attributed to Markus Graefen.

At least 19 recordsLinked to original sources
PubMed2007

Tumour volume and high grade tumour volume are the best predictors of pathologic stage and biochemical recurrence after radical prostatectomy.

INTRODUCTION: Our goal was to examine to what extent tumour volume (TV) and percentage of high grade tumour volume (%HGTV) affect the rate of positive surgical margins and the rate of biochemical recurrence after radical prostatectomy. MATERIALS AND METHODS: TV and %HGTV were routinely planimetrically quantified in a cohort of 780 consecutive patients. Mean follow-up was 46.7 months. Multivariable regression models addressed two separate endpoints: positive surgical margins and biochemical recurrence. The increase in model predictive accuracy related to the addition of TV and %HGTV to radical prostatectomy stage and grade was assessed, after 200 bootstrap resamples to reduce overfit bias. RESULTS: In multivariable logistic regression models addressing positive surgical margins rate, predictive accuracy increased by 1.9% (p<0.001) when TV was added to other covariates. No further increment was noted when %HGTV was added (p=0.3). In multivariable Cox regression models addressing biochemical recurrence, accuracy increased by 0.6% (p=0.002) when TV was added and an additional increase of 0.7% was recorded when %HGTV (p<0.001) was added. CONCLUSION: Tumour bulk reflected by TV affects local cancer control rate, which is reflected in the rate of positive surgical margins. Conversely, high grade cancer determines the rate of biochemical recurrence. These two variables represent the most powerful predictors of cancer control in men treated for localised prostate cancer. Moreover, they increase the ability of established predictors to predict the outcomes of interest. In consequence, they warrant consideration in future predictive and prognostic tools.

Adult↗
PubMed2007

Development and external validation of an extended repeat biopsy nomogram.

PURPOSE: We hypothesized that the outcome of repeat biopsy could be accurately predicted. We tested this hypothesis in a contemporary cohort from 3 centers. MATERIALS AND METHODS: The principal cohort of 1,082 men from Hamburg, Germany was used for nomogram development as well as for internal 200 bootstrap validation in 721 and external validation in 361. Two additional external validation cohorts, including 87 men from Milan, Italy and 142 from Seattle, Washington, were also used. Predictors of prostate cancer on repeat biopsy were patient age, digital rectal examination, prostate specific antigen, percent free prostate specific antigen, number of previous negative biopsy sessions and sampling density. Multivariate logistic regression models were used to develop the nomograms. RESULTS: The mean number of previous negative biopsies was 1.5 (range 1 to 6) and the mean number of cores at final repeat biopsy was 11.1 (range 10 to 24). Of the men 370 (30.2%) had prostate cancer. On multivariate analyses all predictors were statistically significant (p < or =0.028). After internal validation the nomogram was 76% accurate. External validation showed 74% (Hamburg), 78% (Milan) and 68% (Seattle) accuracy. CONCLUSIONS: Relative to the previous nomograms (10 predictors or 71% accuracy) our tool relies on fewer variables (6) and shows superior accuracy in European men. Accuracy in American men is substantially lower. Racial, clinical and biochemical differences may explain the observed discrepancy in predictive accuracy.

Adult↗
PubMed2006

Prediction of pathological stage is inaccurate in men with PSA values above 20 ng/mL.

INTRODUCTION: We hypothesized that either very low (0-2.5 ng/mL) or very high (>20 ng/mL) PSA values may limit the accuracy of pathological stage predictions. To test this hypothesis, we examined 5193 consecutive patients subjected to radical prostatectomy (RP) for localized prostate cancer (PCa). MATERIAL AND METHODS: Patients were divided into three cohorts according to their pre-treatment PSA value: </=2.5 (n=331), 2.51-20 (n=4545) and >20 ng/mL (n=317). Subsequently in each cohort, the ability of PSA, clinical stage and biopsy Gleason sum was tested in multivariable logistic regression models predicting three separate endpoints: extracapsular extension (ECE), seminal vesicle invasion (SVI) and lymph node invasion (LNI). Predictive accuracy represented the performance benchmark. All models were adjusted for year of surgery and subjected to 200 bootstrap resamples to reduce overfit bias. RESULTS: For PSA </=2.5 ng/mL, predictive accuracy was 76.7%, 72.3% and 82.8% for respectively ECE, SVI and LNI. For PSA 2.51-20 ng/mL, the predictive accuracy for the same endpoints was 67.8%, 77.4% and 81.6%. Finally, for PSA >20 ng/mL, predictive accuracy was 63.6%, 63.7% and 70.6%. CONCLUSIONS: The ability to predict pathological stage in patients with PSA values in excess of 20 ng/mL significantly decreased, compared to patients with lower PSA values. Therefore, accurate staging of these patients may require alternative markers or staging schemes.

Adult↗
PubMed2006

Development and internal validation of preoperative transition zone prostate cancer nomogram.

OBJECTIVES: Up to 20% of men may harbor a transition zone (TZ) prostate cancer (PCa) at radical prostatectomy (RP). TZ PCa may be associated with more favorable RP pathologic findings than peripheral zone (PZ) PCa. To identify these men, we developed a model capable of predicting the probability of TZ PCa at RP. METHODS: The study cohort consisted of 945 consecutive men treated with RP, with clinical stage, prostate-specific antigen (PSA) level, and detailed biopsy and RP pathology data available. The preoperative variables were used as predictors in the multivariate logistic regression models to predict the rate of TZ PCa at RP. PCa was defined as a TZ tumor when more than 50% of the planimetrically measured tumor volume was situated within the TZ. Regression coefficients were used to develop nomograms, which were subjected to 200 bootstrap resamples to reduce overfit bias. RESULTS: TZ PCa at the final pathologic examination was recorded in 110 patients (11.6%). After 200 bootstraps, the most parsimonious and most accurate nomogram was 77.3% accurate in predicting the probability of TZ PCa. CONCLUSIONS: This nomogram is ideally suited to identify patients with markedly elevated, nearly metastatic serum PSA levels who harbor a TZ tumor that is highly treatable by RP.

Adult↗
PubMed2006

Body mass index does not improve the ability to predict biochemical recurrence after radical prostatectomy.

PURPOSE: To test whether body mass index (BMI) improves pre- or post-operative biochemical recurrence (BCR) predictions after radical prostatectomy. MATERIALS AND METHODS: Pre- and post-operative data were available in 2416 and 2499 men, respectively. Cox regression models addressed the association between BMI and the rate of BCR after adjusting for pre- and post-operative predictors. Predictive accuracy was quantified using Harrell's concordance index, with and without BMI and subjected to 200 bootstraps to reduce overfit bias. Differences in predictive accuracy were compared using the Mantel-Haenszel test. RESULTS: After adjusting for either pre- or post-operative variables, increasing BMI was a statistically independent risk factor of BCR in both models (both p0.003). Its addition to pre- and post-operative variables respectively increased predictive accuracy measures from 69.6 to 70.2% (+0.6%, p=0.7) and from 78.1 to 78.4% (+0.3%, p=0.8). CONCLUSION: Our data emphasise that despite its significance, inclusion of BMI into models, to predict BCR, does not improve their accuracy.

Body Mass Index↗
PubMed2006

Surgical volume is related to the rate of positive surgical margins at radical prostatectomy in European patients.

OBJECTIVE: To assess the association between surgical volume (SV) and the rate of positive surgical margins (PSM) after radical prostatectomy (RP) in a large single-institution European cohort of patients. PATIENTS AND METHODS: In all, 2402 men had a RP by a group of 11 surgeons, all of whom were trained by the surgeon with the highest SV; all surgeons used the same surgical technique. Variables assessed before RP were prostate-specific antigen (PSA) level, clinical stage and biopsy Gleason sum; variables assessed after RP were PSA level, extracapsular extension, seminal vesicle invasion, lymph node invasion and pathological Gleason sum. These were used to predict the rate of PSM in models before or after RP. Multivariate models were complemented with SV to test its independent and multivariate statistical significance and to quantify its impact on the model's overall (and 200 bootstrap-corrected) predictive accuracy. RESULTS: The mean (range) SV was 201 (1-1293) RPs; the mean (median, range) rate of PSM was 20.2 (21.4, 0-32.9)%. In multivariate models, SV was a highly statistically significant independent predictor of PSM (P < 0.001) and increased the predictive accuracy in multivariate models both before (2.0%) and after RP (1.5%, both P < 0.001). However, when the surgeon with the highest SV, who contributed to 1293 cases, was removed from the analyses, the multivariate independent prediction and the gains in predictive accuracy related to adding SV, disappeared in the models both before (P = 0.9, accuracy gain 0.1%) and after (P = 0.4, accuracy gain - 0.3%) RP. CONCLUSIONS: These results indicate that patients treated by surgeons with a very high volume can expect to have a significantly lower rate of PSM, after accounting for clinical and pathological case-mix differences. However, SV is not a predictor of PSM when analyses are restricted to intermediate- and low-volume surgeons.

Clinical Competence↗
PubMed2006

Development and external validation of an extended 10-core biopsy nomogram.

OBJECTIVES: To test the accuracy of a previously externally validated sextant biopsy nomogram in referred men exposed to > or =10 or more biopsy cores. Moreover, we explored the hypothesis that a more accurate predictive tool could be developed. METHODS: Previous nomogram predictors (age, digital rectal examination, prostate-specific antigen, and percent free PSA) were used to assess the accuracy of our previous nomogram in a cohort consisting of 2900 men referred for prostatic evaluation. Moreover, these variables were complemented with sampling density (SD) (i.e., ratio of gland volume and the number of planned biopsy cores) within multivariable logistic regression models (LRM) predicting presence of prostate cancer (pCA) on the initial 10 or more core biopsy. The LRMs were used to develop and internally validate (200 bootstrap resamples) a new nomogram in 1162 men from Hamburg, Germany. The LRMs' external validity was tested in three separate cohorts (Hamburg, n=582; Milan, n=961; Seattle, n=195). RESULTS: The contemporary external validation of the previously validated sextant nomogram demonstrated 70% accuracy. Internal validation of the new nomogram demonstrated 77% accuracy, and external cohorts demonstrated 73-76% accuracy. CONCLUSIONS: In the era of extended biopsy schemes, previously developed predictive models are less accurate in predicting the probability of pCA on initial biopsy. We developed a new tool that allows obtaining more accurate predictions. Moreover, before biopsy, it also allows defining the ideal ratio between gland volume and the number of planned biopsy cores that would yield the ideal biopsy rate.

Adult↗
PubMed2006

Prostate cancer nomograms: an update.

OBJECTIVE: Several nomograms have been developed to predict outcomes related to prostate cancer (PCa). METHODS: We provide a descriptive and an analytic comparison of nomograms. Further, we report a set of recent PCa nomograms, in which we recorded predictor variables, number of patients used to develop each nomogram, and nomogram-specific features. Moreover, accuracy estimates and type of validation are considered. RESULTS: Our findings suggest a demand for updated nomograms in selected fields of PCa outcomes. Moreover, an increasing number of nomograms address important end points such as prostate-specific antigen recurrence, distant metastases, or androgen-independent PCa-specific survival. CONCLUSION: Our results suggest that nomograms are available for many PCa-related outcomes. They represent a valid methodologic approach if correct criteria are met.

Biopsy↗
PubMed2006

Initial biopsy outcome prediction--head-to-head comparison of a logistic regression-based nomogram versus artificial neural network.

OBJECTIVES: Nomograms and artificial neural networks (ANNs) represent alternative methodologic approaches to predict the probability of prostate cancer on initial biopsy. We hypothesized that, in a head-to-head comparison, one of the approaches might demonstrate better accuracy and performance characteristics than the other. METHODS: A previously published nomogram, which relies on age, digital rectal examination, serum prostate-specific antigen (PSA), and percent-free PSA, and an ANN, which relies on the same predictors plus prostate volume, were applied to a cohort of 3980 men, who were subjected to multicore systematic prostate biopsy. The accuracy and the performance characteristics were compared between these two approaches. RESULTS: The accuracy of the nomogram was 71% versus 67% for the ANN (p=0.0001). Graphical exploration of the performance characteristics demonstrated virtually perfect predictions for the nomogram. Conversely, the ANN underestimated the observed rate of prostate cancer. CONCLUSIONS: A 4% increase in predictive accuracy implies that the use of the nomogram instead of the ANN will result in 40 additional patients who will be correctly classified between benign and cancer.

Adult↗
PubMed2006

Zonal origin of localized prostate cancer does not affect the rate of biochemical recurrence after radical prostatectomy.

OBJECTIVE: To investigate whether transition zone (TZ) prostate cancers demonstrate different rates of biochemical recurrence after radical prostatectomy compared to peripheral zone (PZ) cancers. METHODS: In 1262 consecutive patients treated with radical prostatectomy, computerized planimetry defined tumour origin as either TZ tumours (>70% TZ location) or PZ. Kaplan-Meier and multivariate Cox regression models tested the association between zonal origin and the rate of biochemical recurrence (prostate-specific antigen >0.1ng/ml and rising). We used the Harrell's concordance index to quantify the accuracy of various Cox regression models. RESULTS: TZ prostate cancers were diagnosed in 115 patients (9.1%). Biochemical recurrence was recorded in 16 TZ and in 201 PZ prostate cancers patients. In multivariate Cox models, the rate of biochemical recurrence was not significantly different between TZ and PZ prostate cancers (p=0.4). Combined multivariate predictive accuracy of biochemical recurrence predictions was 81.2% accurate when zonal origin was included versus 81.0% when zonal origin was omitted. CONCLUSIONS: The zonal origin of prostate cancers does not affect the rate of biochemical recurrence after radical prostatectomy.

Humans↗
PubMed2006

Nerve distribution along the prostatic capsule.

OBJECTIVES: Recent literature describes indications for a more-complex course of fibres of the neurovascular bundle (NVB), despite the widely held assumption that it is gathered at the rectolateral side of the prostate. The objective of this study therefore was to determine the typical pattern of nerve distribution along the prostatic capsule. MATERIALS AND METHODS: Permanent sections of 31 patients, who underwent non-nerve-sparing radical prostectomy (RP) at our institution, were investigated. A total of 186 slides taken from the apex, mid-part, and base of the prostate was analyzed by microscopy. Before microscopy, slides were divided into 12 sectors and numbered clockwise starting from "1" for left ventral sides to "6" for the rectal sides (accordingly, "12"-"7" for right half). Every single nerve and ganglion in the prostatic capsule and the periprostatic tissue was counted in each sector. RESULTS: The majority of nerves found in the sectors corresponded to the typical location of the NVB at the rectolateral sides of the prostate (4/5 or 8/9 o'clock sectors). In these two sectors, a median of 45.9-65.6% of counted nerves per half was found. However, a significant amount of nerves (21.5%-28.5%) was detected above the horizontal line. CONCLUSIONS: We conclude that 1/5-1/4 of nerves can be found along the ventral circumference of the prostatic capsule. To preserve a maximum number of nerves, we therefore recommend a modification of the surgical technique by focusing on a high incision for nerve sparing on the ventral parts of the prostate.

Humans↗
PubMed2006

High incidence of prostate cancer detected by saturation biopsy after previous negative biopsy series.

OBJECTIVES: We explored the yield of saturation biopsy and developed a nomogram predicting the probability of prostate cancer (PCa) on the basis of saturation biopsy. MATERIALS AND METHODS: Between 2001 and 2004, saturation biopsies (average of 24 cores) were performed in 161 men with persistently elevated prostate specific antigen (PSA) level (median, 9 ng/ml). All had at least two previously negative, eight-core biopsy sessions. PCa predictors on saturation biopsy were integrated within multivariate nomograms. RESULTS: PCa detection was 41% (n=66 of 161). PSA density and transition zone volume were the most significant predictors of PCa on saturation biopsy. The accuracy of the nomogram with the best performance characteristics was 72%. CONCLUSIONS: Saturation biopsy may be indicated in men with a persistent suspicion of PCa. High-risk individuals can be identified accurately with our nomogram.

Adult↗
PubMed2006

High radical prostatectomy surgical volume is related to lower radical prostatectomy total hospital charges.

OBJECTIVE: To test the hypothesis that individual surgical volume (SV) is an independent predictor of radical prostatectomy (RP) total charges. METHODS: We used the Florida State Inpatient Data File. ICD-9 codes 60.5 (RP) and 185 (prostate cancer) identified all men treated with RP for prostate cancer between January 1 and December 31, 1998. Among 1,923,085 records, 3167 RPs were selected. SV represented the predictor. Total RP charges represented the outcome. Age, race, and comorbidity represented covariates. Univariate and multivariate linear regression models were used. RESULTS: All 3167 RPs were performed by 81 surgeons. SV ranged from 2 to 162 (mean, 68). Charges were 4755 dollars to 140,201 dollars (mean, 18,200 dollars). In the multivariate model, each SV increment corresponding to one RP reduced hospital charges by 25 dollars (p < or = 0.001). CONCLUSIONS: Redistribution of RPs from low to high SV users could result in significant savings. For example, 4 million dollars could be saved if 1000 RPs were redistributed from surgeons with an SV of 18 to surgeons with an SV of 200.

Adult↗
PubMed2006

Frozen section for the management of intraoperatively detected palpable tumor lesions during nerve-sparing scheduled radical prostatectomy.

OBJECTIVES: The intraoperative finding of palpable tumor lesions has been described as a contraindication for nerve-sparing (NS) radical prostatectomy (RP). However, its evaluation is subjective. Especially in patients with a strong demand to regain postoperative erectile function, a surgeon might be reluctant to sacrifice neurovascular bundles (NVBs) based on this information. We investigated the use of frozen section (FS) analysis to monitor the safety and efficiency of NS during RP in patients with intraoperatively identified subcapsular tumor lesions. METHODS: In 83 of 608 patients, who underwent NS-RP, intraoperative FS was performed because of a lesion palpable close to the capsule. A wedge of 4cm in diameter including the lesion was cut off and stained differently for capsule and intraprostatic margin. In case of presence of carcinoma adherent to the capsule, the NVB was resected; otherwise, the NVB remained in situ. RESULTS: Patients with palpable tumor lesions had pT3 tumors in 36% and 61% had Gleason 4 pattern, compared to 18% and 42% for the control group. Carcinoma was found in 93% of the FS specimens. In 42% of the FS samples, tumor had contact with the capsule and 14% of secondary resected NVB specimens demonstrated a carcinoma invasion. In 52% NVBs could be preserved despite an ipsilateral nodule without negatively affecting the margin status. However, the false-negative rate of the FSs was 6%. Conversely, FSs set the intraoperative decision to remove the NVB in 42% of FS patients, resulting in an additional 36% of negative margins. CONCLUSIONS: In patients with intraoperatively detected tumor lesions during a NS planned RP, FS objectively supports the decision of secondary NVB resection as well as preservation.

Carcinoma↗
PubMed2006

Anatomic radical retropubic prostatectomy-long-term recurrence-free survival rates for localized prostate cancer.

Radical prostatectomy remains the mainstay for the treatment of localized prostate cancer. Long-term follow-up data showed excellent cancer control rates in several prostatectomy series. We report biochemical recurrence (BCR) outcomes after radical retropubic prostatectomy (RRP) in a European single center series of patients treated over a 13-year period. Between 1992 and 06/2005, 4,277 consecutive men underwent a RRP at the University Hospital Hamburg Eppendorf, Germany. Kaplan-Meier probabilities of BCR-free survival were determined for those patients with complete preoperative data, postoperative data, and follow-up information. Uni-and multivariate Cox regression models addressed PSA recurrence, defined as a PSA level > or = 0.1 ng/ml. Overall, BCR-free survival ranged between 84, 70 and 61% for 2, 5, and 8 years, respectively. In univariate and multivariate analyses, except for age and type of nerve-sparing technique, all traditional clinical and pathological variables represented statistically independent predictors of PSA recurrence-free survival (all P < or = 0.001). In organ-confined disease, the 10-year recurrence free survival rate was 80 and 30% in non-organ-confined cancers. Our findings confirm excellent long-term biochemical cancer-control outcomes after RRP. High grade prostate cancer at final pathology and seminal vesicle invasion proved to be the strongest risk factors of BCR after surgery.

Adult↗
PubMed2006

Comparative assessment of the 1992 and 2002 pathologic T3 substages for the prediction of biochemical recurrence after radical prostatectomy.

BACKGROUND: The objective of this study was to compare the ability of the 1992 American Joint Committee on Cancer (AJCC) TNM staging system for nonorgan-confined prostate carcinoma (PCa) (pathologic T3 [pT3a], pT3b,and pT3c) to predict biochemical recurrence (BCR) after radical prostatectomy with its revision from 1997/2002 (pT3a and pT3b). METHODS: The authors analyzed prospectively collected data from 971 consecutive patients with pT3 tumors who underwent radical prostatectomy alone at a single institution. According to the 1992 AJCC substages, 494 patients had pT3a PCa (51%), 85 patients had pT3b PCa (9%), 302 patients had pT3c PCa (31%) and 91 patients had pT3 PCa (9%) with metastatic lymph node invasion (LNI). Kaplan-Meier and Cox proportional hazards regression analyses were employed to assess the BCR rate using the preoperative prostate-specific antigen (PSA) level, surgical margin (SM) status, pathologic Gleason score, and LNI. The predictive accuracy of this "base" model was compared with models that added either the AJCC 1992 or the AJCC 1997/2002 staging definitions. RESULTS: BCR was observed in 345 patients (36%). The actuarial 5-year recurrence-free probability for patients with AJCC 1992 pT3a, pT3b, and pT3c PCa was 69%, 42%, and 33%, respectively, and differed significantly between men with pT3a tumors and men with pT3b tumors (log-rank test; P < 0.0005). In Cox regression analyses, the 1992 substages were associated significantly with BCR after controlling for PSA, SM status, Gleason grade, and LNI (P < 0.0005). The predictive accuracy of the base model (bootstrap-corrected concordance index, 0.739) was improved after addition of the 1992 TNM staging criteria (concordance index, 0.747). However, predictive accuracy was similar for the model that included the 1997/2002 substages (concordance index, 0.746). CONCLUSIONS: Substaging of pT3 tumors according to the less complex 1997/2002 pT3 classification improved the predictive accuracy of the BCR rate virtually to the same extent as the more detailed 1992 classification. Therefore, the current data favor the use of the 1997/2002 pT3 substaging system.

Biomarkers, Tumor↗
PubMed2006

The 2002 AJCC pT2 substages confer no prognostic information on the rate of biochemical recurrence after radical prostatectomy.

INTRODUCTION: We examined the prognostic value of AJCC pT2 substages in prediction of biochemical recurrence (BCR) after radical prostatectomy (RP), in European patients. METHODS: A cohort of 1726 RP patients with pT2N0 prostate cancer (PCa) was studied. Multivariate Cox regression models addressed the association between either the 1997 or 1992/2002 pT2 substages after controlling for total PSA, primary and secondary pathologic Gleason scores and surgical margin status and time to PSA recurrence (PSA >0.1 and rising) after RP. Regression coefficients were then used to test the predictive accuracy of multivariate models in a nomogram setting. RESULTS: PSA recurrence occurred in 80 (4.6%) patients. Mean and median times to recurrence were respectively 28.9 and 24.4 months. In univariate analyses, neither the 1997 (p = 0.48) nor the 1992/2002 pT2 substages (p = 0.054) were predictive of recurrence. In multivariate analyses the lack of significance persisted (1997 p = 0.709; 1992/2002 p = 0.124). When either the 1997 or 1992/2002 pT2 substages were added to a multivariate nomogram without pT2 substage information, its accuracy respectively decreased by 0.8% and 1.1%. CONCLUSION: Our data indicate that pT2 substages offer no incremental value relative to pre-treatment total PSA, surgical margin status and pathologic Gleason scores. Therefore, it might be postulated that it is sufficient to confirm organ confinement according to Partin's pathologic staging.

Analysis of Variance↗