Markus Graefen

University Medical Center Hamburg - Eppendorf, Hamburg, Hamburg, Germany

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Publications (690)3181.81 Total impact

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    ABSTRACT: Sequestosome 1 (p62) is a multifunctional adapter protein accumulating in autophagy-defective cells. To evaluate the clinical impact and relationship with key genomic alterations in prostate cancer, p62 protein levels were analyzed by immunohistochemistry on a tissue microarray containing 12,427 prostate cancers. Data on ERG status and deletions of PTEN, 3p13, 5q21 and 6q15 were available from earlier studies. p62 immunostaining was absent in benign prostatic glands but present in 73% of 7,822 interpretable prostate cancers. Strong cytoplasmic p62 staining was tightly linked to high Gleason grade, advanced pathological tumor stage, positive nodal status, positive resection margin, and early PSA recurrence (p<0.0001 each). Increased levels of p62 were significantly linked to TMPRSS2-ERG fusions, both by FISH and immunohistochemical analysis (p<0.0001 each). For example, moderate or strong p62 immunostaining was seen in 28.5% of cancers with TMPRSS2:ERG fusion detected by FISH and in 23.1% of cancers without such rearrangements (p<0.0001). Strong p62 staining was significantly linked to presence of all tested deletions, including PTEN (p<0.0001), 6q15 (p<0.0001), 5q21 (p=0.0002), and 3p13 (p=0.0088), 6q15 (p<0.0001), suggesting a link between p62 accumulation and loss of genomic stability. The prognostic role of p62 protein accumulation was striking and independent of Gleason grade, pT stage, pN stage, surgical margin status and preoperative PSA, irrespective of whether preoperative or postoperative parameters were used for modeling. Our study identifies cytoplasmic accumulation of p62 as a strong predictor of an adverse prognostic behavior of prostate cancer independently from established clinico-pathological findings. Copyright © 2015, American Association for Cancer Research.
    Clinical Cancer Research 04/2015; DOI:10.1158/1078-0432.CCR-14-0620 · 8.19 Impact Factor
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    ABSTRACT: Given the growing body of literature since first description of HistoScanning™ in 2008, there is an unmet need for a contemporary review. Studies addressing HistoScanning™ in prostate cancer (PCa) were considered to be included in the current review. To identify eligible reports, we relied on a bibliographic search of PubMed database conducted in January 2015. Twelve original articles were available to be included in the current review. The existing evidence was reviewed according to the three following topics: prediction of final pathology at radical prostatectomy, prediction of disease stage and application at prostate biopsy. High sensitivity and specificity for HistoScanning™ to predict cancer foci ≥0.5 ml at final pathology were achieved in the pilot study. These results were questioned, when HistoScanning™ derived tumor volume does not correlate with final pathology results. Additionally, HistoScanning™ was not able to provide reliable staging information according to neither extraprostatic extension, nor seminal vesicle invasion prior to radical prostatectomy. Controversy data also exist according to the use of HistoScanning™ at prostate biopsy. Specifically, most encouraging results were recorded in a small patient cohort. Conversely, HistoScanning™ achieved poor prediction of positive biopsies, when relying on larger studies. Finally, the combination of HistoScanning™ and conventional ultrasound achieved lower detection rates than systematic biopsy. Currently, evidence is at best weak and questions whether HistoScanning™ might improve the detection of PCa.
    World Journal of Urology 04/2015; DOI:10.1007/s00345-015-1555-y · 3.42 Impact Factor
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    ABSTRACT: Brachytherapy (BT) is a widely used treatment modality for elderly patients with localized prostate cancer (PCa). To describe the patterns of BT use in octo- and nonagenarians treated for localized PCa in the USA. We hypothesized that most individuals treated with BT should remain alive for at least 10 years. We also postulated that BT should ideally be administered as monotherapy. Using the Surveillance Epidemiology and End Results (SEER)-Medicare-linked database, 2701 octo- and nonagenarians treated with BT between 1992 and 2009 were identified. Cumulative incidence rates and smoothed cumulative incidence plots were used. In patients with low-risk characteristics, 40 % received BT alone; 27 % received BT combined with ADT; 19 % received BT and EBRT; and 14 % received BT combined with both ADT and EBRT. Of intermediate-to-high-risk patients, 19 % received BT alone; 16 % received BT combined with ADT; 19 % received BT combined with EBRT; and 45 % received BT together with ADT and EBRT. Overall survival rate was 79 and 47 % at 5 and 10 years. Less than half of elderly treated with BT remain alive at 10 years of follow-up. Moreover, the vast majority of those individuals not only receives BT, but is also exposed to two or even three combined therapy modalities. These findings are worrisome.
    World Journal of Urology 04/2015; DOI:10.1007/s00345-015-1553-0 · 3.42 Impact Factor
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    ABSTRACT: In a population-based case-control study (PROtEuS), we examined the association between prostate cancer (PCa) and (1) benign prostatic hypertrophy (BPH) history at any time prior to PCa diagnosis, (2) BPH-history reported at least 1 year prior to interview/diagnosis (index date) and (3) exposure to BPH-medications. Cases were 1933 men with incident prostate cancer diagnosed across Montreal French hospitals between 2005 and 2009. Population controls were 1994 men from the same age distribution and residential area. In-person interviews collected socio-demographic characteristics and medical history, e.g., BPH diagnosis, duration and treatment, as well as on PCa screening. Logistic regression analyses tested overall and grade-specific associations, including subgroup analyses with frequent PSA testing. A BPH-history was associated with an increased risk of PCa (OR 1.37 [95 % CI 1.16-2.61]), more pronounced for low-grade PCa (Gleason ≤6: OR 1.54 [1.26-1.87]; Gleason ≥7: OR 1.05 [0.86-1.27]). The association was not significant when BPH-history diagnosis was more than 1 year prior to index date, except for low-grade PCa (OR 1.29 [1.05-1.60]). Exposure to 5α reductase inhibitors (5α-RI) resulted in a decreased risk of overall PCa (OR 0.62 [0.42-0.92]), particularly for intermediate- to high-grade PCa (Gleason ≤6: OR 0.70 [0.43-1.14]; Gleason ≥7: OR 0.43 [0.26-0.72]). Adjusting for PSA testing frequency or restricting analyses to frequently screened subjects did not affect these results. BPH-history was associated with an increased PCa risk, which disappeared, when BPH-history did not include BPH diagnosis within the previous year. Our results also suggest that 5α-RI exposure exerts a protective effect on intermediate and high-grade PCa.
    World Journal of Urology 04/2015; DOI:10.1007/s00345-015-1546-z · 3.42 Impact Factor
  • Derya Tilki, Hartwig Huland, Markus Graefen
    European Urology 03/2015; DOI:10.1016/j.eururo.2015.03.032 · 12.48 Impact Factor
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    ABSTRACT: As life expectancy increases, functional outcomes in elderly patients after radical prostatectomy (RP) become a more important factor to consider in treatment selection. The aim of this study was to determine age-dependant differences in functional outcomes after RP. A total of 8,295 patients who underwent RP from January 2009 to July 2013 were analyzed. Univariate and multivariate logistic regressions were used to estimate the effect of age and other covariates on 3- and 12-month continence and potency rates. Continence was achieved if no more than one safety pad was used per day. Potency was defined as an international index of erectile function (IIEF)-5 score of 18 or higher. In the entire cohort, 12-month (3-mo) continence and potency rates were 91.0% (76.1%) and 54.6% (40.9%), respectively. The 1-year continence rates for age groups<65,≥65 and<70,≥70 and<75, and≥75 years were 93.2%, 90.8%, 86.0%, and 86.5%, respectively. The corresponding 1-year potency rates were 59.3%, 46.9%, 44.4%, and 31.3%. In both, univariate and multivariate analyses, older age had a significant negative effect on functional outcomes. Moreover, nerve sparing, pT category, and patients' body mass index were significantly associated with continence. Nerve sparing, pT category, patients' body mass index, and use of PDE5 inhibitor or intracavernous injection therapy significantly influenced potency. Older age has a significant adverse effect on recovery of continence and potency. Although functional outcomes in elderly patients and especially in patients aged 75 years or older are still good, they should be educated about the increased risk of incontinence and impotence after RP. Copyright © 2015 Elsevier Inc. All rights reserved.
    Urologic Oncology 03/2015; 12. DOI:10.1016/j.urolonc.2015.01.015 · 3.36 Impact Factor
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    ABSTRACT: HOXB13 is a prostate cancer susceptibility gene which shows a cancer predisposing (G84E) mutation in 0.1-0.6% of males. We analyzed the prognostic impact of HOXB13 expression by immunohistochemistry on a tissue microarray containing more than 12,400 prostate cancers. Results were compared to tumor phenotype, biochemical recurrence, androgen receptor (AR) and prostate specific antigen (PSA) as well as molecular subtypes defined by ERG status and genomic deletions of 3p, 5q, 6q, and PTEN. HOXB13 immunostaining was detectable in 51.7% of 10,216 interpretable cancers and considered strong in 9.6%, moderate in 19.7% and weak in 22.3% of cases. HOXB13 expression was linked to advanced pT stage, high Gleason grade, positive lymph node status (p < 0.0001 each), high pre-operative PSA levels (p = 0.01), TMPRSS2:ERG fusion, PTEN deletions, AR expression, cell proliferation, reduced PSA expression and early PSA recurrence (p < 0.0001 each). The prognostic value of HOXB13 was independent from established parameters including Gleason, stage, nodal stage and PSA. Co-expression analysis identified a subset of tumors with high HOXB13 and AR but low PSA expression that had a particularly poor prognosis. HOXB13 appears to be a promising candidate for clinical routine tests either alone or in combination with other markers, including AR and PSA.
    Oncotarget 03/2015; · 6.63 Impact Factor
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    ABSTRACT: Histone deacetylases (HDACs) play an important role in tumor development and progression by modifying histone and non-histone proteins. In the current study we analyzed prevalence and prognostic impact of HDAC1 in prostate cancer. HDAC1 expression was analyzed by immunohistochemistry on a tissue microarray containing more than 12,400 prostate cancer specimens. Results were compared to tumor phenotype, biochemical recurrence, and molecular subtypes defined by ERG status as well as genomic deletions of 3p, 5q, 6q and PTEN. HDAC1 immunostaining was detectable in 75.4% of 9,744 interpretable cancers and considered strong in 15.4%, moderate in 39.4% and weak in 20.7% of cases. High HDAC1 expression was associated with high Gleason grade (p<0.0001), advanced pathological tumor stage (p<0.0001), positive nodal status (p=0.0010), elevated preoperative PSA-level (p=0.0127), early PSA recurrence (p<0.0001) and increased cell proliferation p<0.0001). Moreover, high-level HDAC1 staining was associated with TMPRSS2:ERG rearrangement and ERG expression in prostate cancers (p<0.0001) and was linked to deletions of PTEN (p<0.0001), 6q (p<0.0001) and 5q (p=0.0028) in ERG-negative cancers. The prognostic impact of HDAC1 was independent of established clinicopathological parameters and was mostly driven by ERG-negative cancers as revealed by subgroup analyses. HDAC1 has strong prognostic impact in prostate cancer and might contribute to the development of a fraction of genetically instable and particularly aggressive prostate cancers. HDAC1 measurement might therefore be of clinical value for risk stratification of prostate cancer and should be further evaluated in this regard. Copyright © 2015. Published by Elsevier Inc.
    Experimental and Molecular Pathology 03/2015; 98(3). DOI:10.1016/j.yexmp.2015.03.024 · 2.88 Impact Factor
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    ABSTRACT: To examine the impact of marital status on prostate cancer characteristics at radical prostatectomy and oncological outcome after surgery at a high-volume center. We relied on the Martini-Clinic Prostate Cancer database and investigated 8088 prostate cancer patients treated with radical prostatectomy between January 2000 and March 2011. We analyzed differences in clinical and pathological characteristics according to marital status (married and partnership vs single). Additionally, we relied on multivariable Cox regression analyses to predict biochemical recurrence, metastases and death after radical prostatectomy. Finally, Kaplan-Meier analyses were used in a propensity score-matched cohort, adjusted for clinical and pathological characteristics, to examine differences in biochemical recurrence-free, metastases-free and overall survival according to marital status. According to marital status, no significant differences were recorded within clinical and pathological characteristics (all P > 0.05). The impact of marital status on biochemical recurrence (hazard ratio 1.0, 95% confidence interval 0.9-1.3, P = 0.7), metastases (hazard ratio 1.3, 95% confidence interval 0.8-2.1, P = 0.3) and death (hazard ratio 0.8, 95% confidence interval 0.4-1.6, P = 0.6) after radical prostatectomy was not significant (median follow up 48 months). Kaplan-Meier analyses recorded no significant differences for biochemical recurrence-free, metastases-free and overall survival (all log-rank P > 0.05) according to marital status. Marital status does not affect the clinical and pathological characteristics of radical prostatectomy patients treated at a high-volume center. Furthermore, marital status does not affect biochemical recurrence-free and metastases-free survival after radical prostatectomy. © 2015 The Japanese Urological Association.
    International Journal of Urology 03/2015; DOI:10.1111/iju.12717 · 1.80 Impact Factor
  • Hartwig Huland, Markus Graefen
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    ABSTRACT: The use of prostate-specific antigen (PSA) for screening or early detection of prostate cancer (PCa) results in significant stage migration toward more favorable stages and a proven decrease in PCa mortality but is accompanied by substantial rates of overdiagnosis and overtreatment. Acknowledgement of these downsides and endeavors to avoid them have led to substantial changes in treatment patterns. Many centers have reported dramatic changes, with increases in active surveillance (AS) of early cancers and local treatment of advanced disease. To estimate the impact of this development on our radical prostatectomy (RP) series, we analyzed changes in cancer and patient selection over the past 15 yr. Despite a trend toward decreased utilization of RP in Germany, the annual caseload at our institution increased due to regionalization, from 382 RPs in 2000 to 2145 in 2011, and has been stable for the past 3 yr (2106 RPs in 2014). The rate of RPs performed in patients with low-risk PCa, AS candidates, or men with a pure Gleason 6 pattern in the RP specimen dropped from 60%, 38.2%, and 56.2%, respectively, in 2004 to 27%, 14.7%, and 10%, respectively, in 2011–2013. Patients undergoing RP with solely Gleason 6 cancer were younger on average (aged 61 yr) than patients in higher risk groups (aged 65 yr). The rate of histologically insignificant PCa was low, ranging from 1% to 8.8% depending on the definition used. Patient selection is the other important tool used to avoid overtreatment. Long-term other-cause mortality (OCM) should be low in adequately selected RP candidates, and after a minimum follow-up of 15 yr, overall OCM was 14.8%. The OCM rate was 10.2% in men aged <65 yr and 24.3% in men aged ≥65 yr. The current analysis documents a clear shift in utilization of RP toward significant PCa in men with long life expectancy. Based on patient and cancer selection as described, the long-standing discussion of overtreatment with RP might become invalid.
  • Oncotarget 02/2015; · 6.63 Impact Factor
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    ABSTRACT: To predict biochemical recurrence respecting the natural course of pT2 prostate cancer with positive surgical margin (R1) and no adjuvant/neoadjuvant therapy. A multicenter data analysis of 956 patients with pT2R1N0/Nx tumors was performed. Patients underwent radical prostatectomy between 1994 and 2009. No patients received neoadjuvant or adjuvant therapy. All prostate specimens were re-evaluated according to a well-defined protocol. The association of pathological and clinical features, in regard to BCR, was calculated using various statistical tests. With a mean follow-up of 48 months, BCR was found in 25.4 %. In univariate analysis, multiple parameters such as tumor volume, PSA, Gleason at positive margin were significantly associated with BCR. However, in multivariate analysis, Gleason score (GS) of the prostatectomy specimen was the only significant parameter for BCR. Median time to recurrence for GS ≤ 6 was not reached; 5-year BCR-free survival was 82 %; and they were 127 months and 72 % for GS 3+4, 56 months and 54 % for GS 4 + 3, and 27 months and 32 % for GS 8-10. The retrospective approach is a limitation of our study. Our study provides data on the BCR in pT2R1-PCa without adjuvant/neoadjuvant therapy and thus a rationale for an individual's risk stratification. The data support patients and physicians in estimating the individual risk and timing of BCR and thus serve to personalize the management in pT2R1-PCa.
    World Journal of Urology 02/2015; DOI:10.1007/s00345-015-1510-y · 3.42 Impact Factor
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    ABSTRACT: No data exist on the patterns of biochemical recurrence (BCR) and their effect on survival in patients with high-risk prostate cancer (PCa) treated with surgery. The aim of our investigation was to evaluate the natural history of PCa in patients treated with radical prostatectomy (RP) alone. Overall, 2,065 patients with high-risk PCa treated with RP at 7 tertiary referral centers between 1991 and 2011 were identified. First, we calculated the probability of experiencing BCR after surgery. Particularly, we relied on conditional survival estimates for BCR after RP. Competing-risks regression analyses were then used to evaluate the effect of time to BCR on the risk of cancer-specific mortality (CSM). Median follow-up was 70 months. Overall, the 5-year BCR-free survival rate was 55.2%. Given the BCR-free survivorship at 1, 2, 3, 4, and 5 years, the BCR-free survival rates improved by+7.6%,+4.1%,+4.8%,+3.2%, and+3.7%, respectively. Overall, the 10-year CSM rate was 14.8%. When patients were stratified according to time to BCR, patients experiencing BCR within 36 months from surgery had higher 10-year CSM rates compared with those experiencing late BCR (19.1% vs. 4.4%; P<0.001). At multivariate analyses, time to BCR represented an independent predictor of CSM (P<0.001). Increasing time from surgery is associated with a reduction of the risk of subsequent BCR. Additionally, time to BCR represents a predictor of CSM in these patients. These results might help provide clinicians with better follow-up strategies and more aggressive treatments for early BCR. Copyright © 2015 Elsevier Inc. All rights reserved.
    Urologic Oncology 02/2015; DOI:10.1016/j.urolonc.2014.11.018 · 3.36 Impact Factor
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    ABSTRACT: Objective To analyze oncological and functional outcomes of salvage radical prostatectomy (SRP) in patients with recurrent prostate cancer (PCa) and to compare outcomes of patients within and outside the EAU guideline criteria (organ-confined PCa ≤ T2b, Gleason score ≤ 7 and preoperative PSA < 10 ng/mL) for SRP.Patients and MethodsA total of 55 patients who underwent SRP from January 2007 to December 2012 were retrospectively analyzed. Kaplan-Meier curves assessed time to biochemical recurrence (BCR), metastasis-free survival (MFS) and cancer specific survival (CSS). Cox regressions addressed factors influencing BCR and MFS. BCR was defined as PSA>0.2 ng/ml and rising, continence as the use of 0-1 safety pad per day and potency as an IIEF-5 score ≥18.ResultsMedian follow-up was 36 months. Following SRP 42.0% of the patients experienced BCR, 15.9% developed metastasis and 5.5% died from PCa. Patients fulfilling EAU guideline criteria were less likely to have positive lymph nodes and had significantly better BCR-free survival (5-year BCR-free survival 73.9% vs. 11.6% (p=0.001), respectively). In multivariate analysis, LDR-brachytherapy as primary treatment (p=0.03) and presence of positive lymph nodes at SRP (p=0.02) were significantly associated with worse BCR-free survival. The presence of positive lymph nodes or Gleason score > 7 at SRP were independently associated with metastasis. Urinary continence-rate 1 year after SRP was 74%. Seven patients (12.7%) experienced complications ≥III (Clavien grade).Conclusion Salvage radical prostatectomy is a safe procedure providing good cancer control and reasonable urinary continence. Oncologic outcomes are significantly better in patients who met EAU guideline recommendations.This article is protected by copyright. All rights reserved.
    BJU International 02/2015; DOI:10.1111/bju.13103 · 3.13 Impact Factor
  • Katharina Boehm, Markus Graefen
    Nature Reviews Urology 01/2015; DOI:10.1038/nrurol.2014.359 · 4.52 Impact Factor
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    ABSTRACT: Objectives To report pre-specified and exploratory results on the effect of different surgical approaches on erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) obtained from the multicenter, randomized, double-blind, double-dummy REACTT trial of tadalafil (once a day [OaD] or on-demand [pro-re-nata, PRN]) versus placebo.Patients and Methods Patients <68yrs with normal preoperative EF who underwent nsRP for localized prostate cancer (Gleason ≤7, PSA <10ng/mL) were randomized post-nsRP 1:1:1 to 9-month double-blind treatment (DBT) with tadalafil 5mg OaD, tadalafil 20mg PRN, or placebo, followed by 6-week drug-free washout, and 3-month open-label OaD treatment (all patients). EF-recovery was defined as an International Index of Erectile Function (IIEF)-EF domain score ≥22, and normal orgasmic function was defined based on IIEF Question 10. Both parameters were analyzed at the end of washout using logistic regression including terms for: treatment, country, visit, visit-by-treatment interaction, age group, nerve-sparing score (perfect =2, non-perfect >2), and surgical approach (open surgery, robot-assisted laparoscopy, conventional laparoscopy, other). Time to EF-recovery was analyzed post-hoc with a Cox proportional-hazards model including terms for: treatment, age-group, country, surgical approach, and surgery-by-treatment interaction.ResultsOf 422 patients treated, 189 underwent open surgery, 115 robot-assisted laparoscopy, 88 conventional laparoscopy, and 30 surgery classified as “other”. The odds of achieving EF-recovery at the end of drug-free washout were approximately twice as high for the robot-assisted laparoscopy group compared with the open surgery group (odds ratio: 2.42; 95%CI 1.24, 4.72; p=0.029). Patients who underwent robot-assisted laparoscopy were significantly more likely to recover during DBT compared with patients who underwent open surgery (hazard ratio: 1.92; 95%CI 1.17, 3.15; p=0.010). A favourable effect of conventional laparoscopy compared with open surgery could not be observed.Conclusion These results may provide further insights into the role of surgery on EF-recovery post-nsRP. However, the trial was not designed for these analyses and further prospective studies are needed.
    BJU International 01/2015; DOI:10.1111/bju.13030 · 3.13 Impact Factor
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    ABSTRACT: BACKGROUND An increased tumor volume threshold (<2.5 ml) is suggested to define insignificant prostate cancer (iPCa). We hypothesize that an increasing tumor volume within iPCa patients increases the risk of biochemical recurrence (BCR) after radical prostatectomy (RP).METHODS We relied on RP patients treated between 1992 and 2008. Multivariable Cox regression analyses predicting BCR within patients harboring favorable pathological characteristics (≤pT2, pN0/Nx, Gleason 3 + 3). Kaplan–Meier analysis was performed for BCR-free survival within iPCa patients (≤pT2, pN0/Nx, Gleason 3 + 3, tumor volume: <0.5 vs. 0.5–2.49 ml).RESULTSFrom 1,829 patients, 141 (7.7%) and 310 (16.9%) harbored iPCa (tumor volume: <0.5 vs. 0.5–2.49 ml), respectively. Of those, 21 (14.9%) versus 31 (10.0%) had PSA >10 ng/ml. Tumor volume achieved independent predictor status for BCR. Specifically, iPCa patients with increasing tumor volume (0.5–2.49 ml) were at higher risk of BCR after RP than those with tumor volume <0.5 ml (HR: 8.8, 95% CI: 1.2–65.9, P = 0.04). Kaplan–Meier analysis recorded superior BCR-free survival in iPCa patients with lower tumor volume (<0.5 ml) (log-rank P = 0.009). The 10-year cancer-specific death rate was 0 versus 0.5%.CONCLUSIONS Contemporary iPCa definition incorporates intermediate and high-risk patients (PSA: 10–20 and >20 ng/ml). Despite most favorable pathological characteristics, iPCa patients are not devoid of BCR after RP. Moreover, iPCa patients were at higher risk of BCR, when increasing tumor volume up to 2.49 ml was at play. Taken together the contemporary concept of iPCa is suboptimal. Especially, an increased tumor volume threshold for defining iPCa cannot be recommended according to our data. Clinicians might take these considerations into account during decision-making process. Prostate © 2014 Wiley Periodicals, Inc.
    The Prostate 01/2015; 75(1). DOI:10.1002/pros.22889 · 3.57 Impact Factor
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    ABSTRACT: The Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score predicts prostate cancer (PCa) recurrence based on pathologic information from radical prostatectomy (RP). CAPRA-S has never been externally validated in a European cohort. We independently validated the CAPRA-S in a European, single-institution database. The study cohort comprised of 14532 patients treated with radical prostatectomy between January 1992 and August 2012. Prediction of biochemical recurrence (BCR), metastasis and cancer-specific mortality (CSM) by CAPRA-S was assessed by Kaplan-Meier analysis and the c-index. Performance of CAPRA-S in predicting BCR was assessed by calibration plot and decision curve analysis. Median follow up was 50.8 months (IQR 25.0 - 96.0). BCR occurred in 20.3% of men at a median time of 21.2 mo (IQR 7.7 - 44.9). When stratifying patients by CAPRA-S risk groups, BCR-free survival estimates at 5 years were 91.4%, 70.4%, and 29.3% for the low, intermediate and high-risk group, respectively. The c-index for CAPRA-S in predicting BCR was 0.80. The c-indices for CAPRA-S in predicting metastasis and CSM were 0.85 and 0.88, respectively. 417 men developed metastasis, and 196 men died from PCa. The postoperative CAPRA-S score was accurate when applied in a European study cohort and predicted biochemical recurrence, metastasis and CSM after RP with c-indices > 0.80. The score can be valuable for decision-making for adjuvant therapy. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
    The Journal of Urology 12/2014; DOI:10.1016/j.juro.2014.12.020 · 3.75 Impact Factor
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    ABSTRACT: The aim of our study was to reexamine the prevalence of baseline cardiovascular (CV) morbidity and the rates of CV mortality in a contemporary cohort of patients with prostate cancer (PCa) exposed to androgen deprivation therapy (ADT). Records of patients aged 65 years and older with metastatic PCa who received ADT were abstracted from the Surveillance, Epidemiology, and End Results-Medicare database between 1991 and 2009. The primary end points comprised 5-year CV mortality rates. Survival rates were stratified according to age and Charlson comorbidity index (CCI). Competing-risks Poisson regression methodologies were performed. Overall, 9596 patients with metastatic PCa treated with ADT were identified. At baseline, 3049 patients (31.8%) had preexisting CV disease. The 5-year CV mortality rates were 9.8% and 14.8% in the overall population and in patients with preexisting CV disease, respectively. The 5-year CV mortality rates increased with advanced age and higher CCI score. In multivariate competing-risks regression analyses, age, year of diagnosis, CV comorbidities, CCI, and marital status represented independent predictors of CV mortality, after accounting for the risk of dying from other causes (all P ≤ .04). Of those, preexisting CV disease contributed to the highest risk of CV mortality. Our study is limited by its retrospective nature. CV mortality represents a common event in patients with metastatic PCa treated with ADT. Preexisting CV disease represented the strongest risk factor. Copyright © 2014 Elsevier Inc. All rights reserved.
    Clinical Genitourinary Cancer 12/2014; DOI:10.1016/j.clgc.2014.12.003 · 1.69 Impact Factor
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    ABSTRACT: The role of additional androgen deprivation therapy (ADT) in prostate cancer (PCa) patients treated with combined HDR brachytherapy (HDR-BT) and external beam radiotherapy (EBRT) is still unknown. Consecutive PCa patients classified as D'Amico intermediate and high-risk who underwent HDR-BT and EBRT treatment ± ADT at our institution between January 1999 and February 2009 were assessed. Multivariable Cox regression models predicting biochemical recurrence (BCR) were performed. BCR-free survival was assessed with Kaplan-Meier analyses. Overall, 392 patients were assessable. Of these, 221 (56.4 %) underwent trimodality (HDR-BT and EBRT and ADT) and 171 (43.6 %) bimodality (HDR-BT and EBRT) treatment. Additional ADT administration reduced the risk of BCR (HR: 0.4, 95 % CI: 0.3-0.7, p < 0.001). D'Amico high-risk patients had superior BCR-free survival when additional ADT was administered (log-rank p < 0.001). No significant difference for BCR-free survival was recorded when additional ADT was administered to D'Amico intermediate-risk patients (log-rank p = 0.2). Additional ADT administration improves biochemical control in D'Amico high-risk patients when HDR-BT and EBRT are combined. Physicians should consider the oncological benefit of ADT administration for these patients during the decision-making process.

Publication Stats

10k Citations
3,181.81 Total Impact Points


  • 1998–2015
    • University Medical Center Hamburg - Eppendorf
      • Department of Urology
      Hamburg, Hamburg, Germany
  • 2006–2014
    • Prostate Cancer Research Institute
      Los Ángeles, California, United States
  • 2013
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
  • 1998–2013
    • University of Hamburg
      • Department of Urology
      Hamburg, Hamburg, Germany
  • 2012
    • Cornell University
      Итак, New York, United States
  • 2007–2012
    • Università Vita-Salute San Raffaele
      Milano, Lombardy, Italy
    • University of Milan
      Milano, Lombardy, Italy
    • University of Texas at Dallas
      Richardson, Texas, United States
  • 2011
    • Institut Paoli Calmettes
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2005–2011
    • Université de Montréal
      • Department of Surgery
      Montréal, Quebec, Canada
  • 2010
    • Krankenhaus Düren gem. GmbH
      Düren, North Rhine-Westphalia, Germany
    • CUNY Graduate Center
      New York City, New York, United States
  • 2009–2010
    • Schön Klinik Hamburg
      Hamburg, Hamburg, Germany
    • University Hospital Essen
      • Klinik für Urologie
      Essen, North Rhine-Westphalia, Germany
    • Centre hospitalier de l'Université de Montréal (CHUM)
      Montréal, Quebec, Canada
  • 2002–2009
    • Memorial Sloan-Kettering Cancer Center
      • Epidemiology & Biostatistics Group
      New York, New York, United States
    • University of Turku
      Turku, Varsinais-Suomi, Finland
  • 2000–2003
    • Lund University
      • • Department of Laboratory Medicine, Lund
      • • Department of Chemistry
      Lund, Skåne, Sweden