Publications by authors named "Herbert Augustin"

35 Publications

Seasonal Variations in the Diagnosis of Testicular Germ Cell Tumors: A National Cancer Registry Study in Austria.

Cancers (Basel) 2021 Oct 27;13(21). Epub 2021 Oct 27.

Department of Urology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.

We conducted a retrospective National Cancer Registry study in Austria to assess a possible seasonal variation in the clinical diagnosis of testicular germ cell tumors (TGCT). In total, 3615 testicular cancer diagnoses were identified during an 11-year period from 2008 to 2018. Rate ratios for the monthly number of TGCT diagnoses, as well as of seasons and half-years, were assessed using a quasi-Poisson model. We identified, for the first time, a statistically significant seasonal trend ( < 0.001) in the frequency of monthly newly diagnosed cases of TGCT. In detail, clear seasonal variations with a reduction in the tumor incidence during the summer months (Apr-Sep) and an increase during the winter months (Oct-Mar) were observed ( < 0.001). Focusing on seasonality, the incidence during the months of Oct-Dec ( = 0.008) and Jan-Mar ( < 0.001) was significantly higher compared to the months of Jul-Sep, respectively. Regarding histopathological features, there is a predominating incidence in the winter months compared to summer months, mainly concerning pure seminomas ( < 0.001), but not the non-seminoma or mixed TGCT groups. In conclusion, the incidence of TGCT diagnoses in Austria has a strong seasonal pattern, with the highest rate during the winter months. These findings may be explained by a delay of self-referral during the summer months. However, the hypothetical influence of vitamin D3 in testicular carcinogenesis underlying seasonal changes in TGCT diagnosis should be the focus of further research.
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http://dx.doi.org/10.3390/cancers13215377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582382PMC
October 2021

Systematic biopsy should not be omitted in the era of combined magnetic resonance imaging/ultrasound fusion-guided biopsies of the prostate.

Int Urol Nephrol 2021 Nov 9;53(11):2251-2259. Epub 2021 Sep 9.

Department of Urology and Andrology, Klinikum Klagenfurt, Feschnigstrasse 11, 9020, Klagenfurt, Austria.

Purpose: To evaluate prostate cancer detection rates with classical trans-rectal ultrasound-guided systematic 10-core biopsies (SB), targeted biopsies (TB) guided by magnetic resonance (MR)/US fusion imaging and their combination in biopsy-naïve and patients with previously negative prostate biopsies. We compared pathology results after radical prostatectomy with biopsy findings.

Methods: Consecutive patients with prostate imaging-reporting and data system lesions grade ≥ 3 submitted to MRI/US-guided TB and subsequent standard 10-core SB between December 2015 and June 2019 were analyzed.

Results: Detection rate (TB- or SB-positive) in 563 included patients (192 naïve, 371 with previous biopsies) was 56.7% (67.7% for the first, 50.9% for repeated biopsies). With TB (disregarding SB), the rates were 41.4%, 52.1% and 35.8%, respectively. With SB (disregarding TB), the rates were 49.1%, 63.0% and 41.8%, respectively. Eventually, 118 patients underwent surgery and clinically significant cancer was found in 111 (94.1%) specimens. Of those, 23 (20.7%) would have been missed had we relied upon a negative TB and 14 (12.6%) would have been missed had we relied upon a negative SB, disregarding a positive finding on the alternative biopsy template.

Conclusion: SB should not be omitted since TB and SB combination have higher detection rate of clinically relevant prostate cancer than either procedure alone.
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http://dx.doi.org/10.1007/s11255-021-02989-2DOI Listing
November 2021

A rare case of cancer-to-cancer metastasis: breast cancer to renal cell cancer : Case report and review of literature.

Wien Med Wochenschr 2019 Oct 30;169(13-14):350-353. Epub 2019 Apr 30.

Department of Obstetrics and Gynecology, Division of Gynecology, Medical University of Graz, Auenbruggerplatz 14, 8036, Graz, Austria.

Background: Cancer-to-cancer metastasis is very rare with less than 50 cases described in literature. This article reports a case of breast cancer with synchronous metastasis to clear cell renal cell cancer.

Case Description: A 79-year-old woman was diagnosed with a bilateral breast carcinoma. Sonographic staging investigation of the abdomen revealed a 6 cm wide expansion of the right kidney. Bilateral mastectomy and nephrectomy of the right kidney was performed. The histology revealed a clear cell renal cell carcinoma and in the center of the tumor a 0.5 cm metastasis of the breast cancer. The patient's comorbidities and performance status precluded chemotherapy und she received palliative radiotherapy, targeted monoclonal antibody therapy and antihormonal treatment.

Conclusions: Even if cancer-to-cancer metastasis is a very rare phenomenon, the simultaneous or consecutive finding of a renal tumor in women with breast cancer should be carefully evaluated.
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http://dx.doi.org/10.1007/s10354-019-0694-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785643PMC
October 2019

Prognostic value of B7-H1, B7-H3 and the stage, size, grade and necrosis (SSIGN) score in metastatic clear cell renal cell carcinoma.

Cent European J Urol 2019 14;72(1):23-31. Epub 2019 Mar 14.

Department of Urology, Medical University of Graz, Graz, Austria.

Introduction: We compared the potential prognostic impact of B7-H1 and B7-H3 glycoprotein expressions with the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score in metastatic clear cell renal cell carcinoma (mccRCC) during a long term follow-up.

Material And Methods: We investigated 44 mccRCC patients, who underwent radical nephrectomy between 1995 and 2006 at a single tertiary academic center and received interferon therapy (IFNT) for at least three months. The SSIGN score was applied as a validated prediction outcome model. Representative tumor sections were immunostained with anti-B7-H3 and anti-B7-H1 antibodies. Hereafter, positive antigen-antibody reactions were measured using the Positive-Pixel-Count Algorithm of the Aperio-Technology Image Scope software.

Results: In total, 48% of patients were treated with cytoreductive nephrectomy and postoperative IFNT due to synchronous mccRCC, whereas 52% received IFNT after developing metachronous mccRCC. The SSIGN score was independently associated with a higher mortality risk. Patients with a SSIGN score ≤9 showed an extended 'nephrectomy to start of INFT'-interval (p = 0.02), less synchronous clinical metastases (p = 0.0002), as well as an increased median overall - (OS) or cancer-specific survival (CSS) (p = 0.01), respectively. Furthermore, B7-H3 expression levels of ≤16% were associated with an improved OS or CSS and correlated with a more frequent pathologic grade 1-2, as well as a longer 'nephrectomy to start of IFNT'-interval, respectively. B7-H1 expression patterns did not correlate with survival.

Conclusions: The SSIGN score demonstrated the best prognostic performance. In contrast, B7-H3 expression patterns showed a low association with histopathological parameters, but predicted the cut-off-dependent impaired survival and in the future may define a cut-off to indicate checkpoint-inhibitor treatment.
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http://dx.doi.org/10.5173/ceju.2018.1858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469004PMC
March 2019

The Long-Term Effect of Radical Prostatectomy on Erectile Function, Urinary Continence, and Lower Urinary Tract Symptoms: A Comparison to Age-Matched Healthy Controls.

Biomed Res Int 2017 5;2017:9615080. Epub 2017 Feb 5.

Department of Urology, Medical University of Graz, Graz, Austria.

. To analyze the impact of radical prostatectomy (RPE) on erectile function and lower urinary tract function in comparison to age-matched healthy men. . Patients who underwent radical retropubic prostatectomy completed questionnaires containing the IIEF-5, the Bristol female LUTS questionnaire, and the International Prostate Symptom Score (IPSS). . Patients after RPE were included ( = 363). Age-matched healthy men ( = 363) were included. The mean IIEF-5 of patients aged 61-70 yrs after RPE was 10.4 ± 6.6 versus 18.8 ± 5.3 in the control cohort; the respective values for men aged 71-80 yrs after RPE were 7.2 ± 6.5 versus 13.6 ± 7.7 in the control cohort. Urinary incontinence after RPE was reported in 41.9% (61-70 years) and 37.7% (71-80) versus 7.5% and 15.1% in the control cohort. The mean IPSS of patients after RPE aged 61-70 yrs was 5.0 ± 4.4 versus 5.5 ± 4.9 in the control cohort; the respective values for men aged 71-80 yrs were 6.0 ± 4.9 versus 7.5 ± 5.7 in the healthy cohort. . The negative effect of radical prostatectomy on erectile and urinary incontinence remains substantial. The physiologically declining erectile and lower urinary tract function with ageing reduces the difference between healthy men and those after surgery. Healthy men have a higher IPSS presumably due to the presence of bladder outlet obstruction.
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http://dx.doi.org/10.1155/2017/9615080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316428PMC
April 2017

Whole-genome plasma sequencing reveals focal amplifications as a driving force in metastatic prostate cancer.

Nat Commun 2016 06 22;7:12008. Epub 2016 Jun 22.

Institute of Human Genetics, Medical University of Graz, A-8010 Graz, Austria.

Genomic alterations in metastatic prostate cancer remain incompletely characterized. Here we analyse 493 prostate cancer cases from the TCGA database and perform whole-genome plasma sequencing on 95 plasma samples derived from 43 patients with metastatic prostate cancer. From these samples, we identify established driver aberrations in a cancer-related gene in nearly all cases (97.7%), including driver gene fusions (TMPRSS2:ERG), driver focal deletions (PTEN, RYBP and SHQ1) and driver amplifications (AR and MYC). In serial plasma analyses, we observe changes in focal amplifications in 40% of cases. The mean time interval between new amplifications was 26.4 weeks (range: 5-52 weeks), suggesting that they represent rapid adaptations to selection pressure. An increase in neuron-specific enolase is accompanied by clonal pattern changes in the tumour genome, most consistent with subclonal diversification of the tumour. Our findings suggest a high plasticity of prostate cancer genomes with newly occurring focal amplifications as a driving force in progression.
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http://dx.doi.org/10.1038/ncomms12008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917969PMC
June 2016

Is There a Role for Active Surveillance in Low-Risk Prostate Cancer?

Urol Int 2015 17;95(2):125-31. Epub 2015 Mar 17.

Department of Urology, Medical University of Graz, Graz, Austria.

Background: Active surveillance (AS) represents an expectant treatment strategy for clinically localized prostate cancer (PCa) with low-risk features.

Objective: The actual management as well as the pros and cons of AS were evaluated.

Methods: A systematic review of the recent literature was performed using the Medline databases.

Conclusions: Since a substantial number of men die with rather than from PCa, there is a considerable role for AS in carefully selected men. AS may also represent a strategy to reduce the burden of overtreatment rooted in intensified PSA testing. Facing the imprecision of risk stratification based on transrectal ultrasound-guided biopsy, accurate clinical staging represents a major medical challenge. Counseling and care require empathy as well as a profound understanding of the biology and the natural history of PCa.
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http://dx.doi.org/10.1159/000371895DOI Listing
June 2016

Sampling of the anterior apical region results in increased cancer detection and upgrading in transrectal repeat saturation biopsy of the prostate.

BJU Int 2016 Apr 14;117(4):592-7. Epub 2015 May 14.

Department of Urology, Medical University of Graz, Graz, Austria.

Objective: To evaluate whether biopsy cores taken via a transrectal approach from the anterior apical region of the prostate in a repeat-biopsy population can result in an increased overall cancer detection rate and in more accurate assessment of the Gleason score.

Patients And Methods: The study was a prospective, randomised (end-fire vs side-fire ultrasound probe) evaluation of 288 men by repeat transrectal saturation biopsy with 28 cores taken from the transition zone, base, mid-lobar, anterior and the anterior apical region located ventro-laterally to the urethra of the peripheral zone.

Results: The overall prostate cancer detection rate was 44.4%. Improvement of the overall detection rate by 7.8% could be achieved with additional biopsies of the anterior apical region. Two tumours featuring a Gleason score 7 could only be detected in the anterior apical region. In three cases (2.34%) Gleason score upgrading was achieved by separate analysis of each positive core of the anterior apical region. A five-fold higher cancer detection rate in the anterior apical region compared with the transition zone could be shown.

Conclusion: Sampling of the anterior apical region results in higher overall cancer detection rate in repeat transrectal saturation biopsies of the prostate. Specimens from this region can detect clinically significant cancer, improve accuracy of the Gleason Scoring and therefore may alter therapy.
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http://dx.doi.org/10.1111/bju.13108DOI Listing
April 2016

Impact of urinary stone volume on computed tomography stone attenuations measured in Hounsfield units in a large group of Austrian patients with urolithiasis.

Cent European J Urol 2014 18;67(3):289-95. Epub 2014 Aug 18.

Department of Urology, Medical University Graz, Austria.

Introduction: To investigate retrospectively the impact of urinary stone volume on computed tomography stone attenuations measured in Hounsfield units in 253 patients with urolithiasis.

Material And Methods: CT scans were performed in 253 patients with suspected urinary stone disease from 2008 to 2010 using CT-Scanner Siemens, SOMATOM, Sensation 64. One experienced radiologist (A.L) who was blinded to the chemical composition of the stones retrospectively reviewed images and analyzed data to determine the composition of the stones. The results were compared with the biochemical analysis results obtained by infrared spectroscopy (100 FTIR, PerkinElmer).

Results: 253 consecutive patients from 2008 to 2010 were included into analysis: 189 males, and 64 females. Mean age was 51.2. According to stone volume, stones were divided into 2 groups: 126 stones with volume of 4.3 mm or more, 127 stones with volume less than 4.3 mm. There was a significant relationship between stone volume and its CT attenuation only in stones with a volume 4.3 mm or more (p <0.05).

Conclusions: We failed to show a significant relationship between stone volume and its attenuations in Hounsfield units. We could not distinguish uric acid stones from non uric acid stones.
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http://dx.doi.org/10.5173/ceju.2014.03.art16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165675PMC
September 2014

Clinical and laboratory profiles of a large cohort of patients with different grades of varicocele.

Cent European J Urol 2013 26;66(1):71-4. Epub 2013 Apr 26.

Department of Urology, Medical University Graz, Austria.

Objective: In this retrospective study we attempted to report our own data on the different clinical parameters in association with the presence and severity of varicocele in a large group of Austrian men.

Methods: The records of 1,111 consecutive patients with clinical varicocele from 1993 to 2010 were evaluated. The presence, grade, and side of any varicocele were recorded. Semen samples, serum FSH, LH, and testosterone levels, and testicular volume were assessed.

Results: The mean age was 28.8 (±7.3) years. Three hundred seventeen (28.5%) patients presented with grade I varicocele, 427 (38.4%) with grade II varicocele, and 367 (33%) with grade III varicocele. Correlation between different grades of varicocele and semen quality indicated an over-representation of oligospermia and asthenoteratospermia in the group of grade III varicocele (p <0.05), whereas other parameters of semen quality showed no significant difference between the three groups. Serum testosterone levels and BMI were significantly associated (p <0.05) with the grade of varicocele, but no association was found with the other parameters analyzed.

Conclusions: Our analysis showed a significant relationship between the grade of varicocele and semen analysis. Moreover, higher testosterone levels and lower body mass index were associated with the higher grade of varicocele and decreased semen quality. More prospective studies are recommended.
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http://dx.doi.org/10.5173/ceju.2013.01.art22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921831PMC
February 2014

Innovations in diagnostic imaging of localized prostate cancer.

World J Urol 2014 Aug;32(4):881-90

Purpose: In recent years, various imaging modalities have been developed to improve diagnosis, staging, and localization of early-stage prostate cancer (PCa).

Methods: A MEDLINE literature search of the time frame between 01/2007 and 06/2013 was performed on imaging of localized PCa.

Results: Conventional transrectal ultrasound (TRUS) is mainly used to guide prostate biopsy. Contrast-enhanced ultrasound is based on the assumption that PCa tissue is hypervascularized and might be better identified after intravenous injection of a microbubble contrast agent. However, results on its additional value for cancer detection are controversial. Computer-based analysis of the transrectal ultrasound signal (C-TRUS) appears to detect cancer in a high rate of patients with previous biopsies. Real-time elastography seems to have higher sensitivity, specificity, and positive predictive value than conventional TRUS. However, the method still awaits prospective validation. The same is true for prostate histoscanning, an ultrasound-based method for tissue characterization. Currently, multiparametric MRI provides improved tissue visualization of the prostate, which may be helpful in the diagnosis and targeting of prostate lesions. However, most published series are small and suffer from variations in indication, methodology, quality, interpretation, and reporting.

Conclusions: Among ultrasound-based techniques, real-time elastography and C-TRUS seem the most promising techniques. Multiparametric MRI appears to have advantages over conventional T2-weighted MRI in the detection of PCa. Despite these promising results, currently, no recommendation for the routine use of these novel imaging techniques can be made. Prospective studies defining the value of various imaging modalities are urgently needed.
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http://dx.doi.org/10.1007/s00345-013-1172-6DOI Listing
August 2014

Tumor-associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencing.

Genome Med 2013 5;5(4):30. Epub 2013 Apr 5.

Institute of Human Genetics, Medical University of Graz, Harrachgasse 21/8, A-8010 Graz, Austria.

Background: Patients with prostate cancer may present with metastatic or recurrent disease despite initial curative treatment. The propensity of metastatic prostate cancer to spread to the bone has limited repeated sampling of tumor deposits. Hence, considerably less is understood about this lethal metastatic disease, as it is not commonly studied. Here we explored whole-genome sequencing of plasma DNA to scan the tumor genomes of these patients non-invasively.

Methods: We wanted to make whole-genome analysis from plasma DNA amenable to clinical routine applications and developed an approach based on a benchtop high-throughput platform, that is, Illuminas MiSeq instrument. We performed whole-genome sequencing from plasma at a shallow sequencing depth to establish a genome-wide copy number profile of the tumor at low costs within 2 days. In parallel, we sequenced a panel of 55 high-interest genes and 38 introns with frequent fusion breakpoints such as the TMPRSS2-ERG fusion with high coverage. After intensive testing of our approach with samples from 25 individuals without cancer we analyzed 13 plasma samples derived from five patients with castration resistant (CRPC) and four patients with castration sensitive prostate cancer (CSPC).

Results: The genome-wide profiling in the plasma of our patients revealed multiple copy number aberrations including those previously reported in prostate tumors, such as losses in 8p and gains in 8q. High-level copy number gains in the AR locus were observed in patients with CRPC but not with CSPC disease. We identified the TMPRSS2-ERG rearrangement associated 3-Mbp deletion on chromosome 21 and found corresponding fusion plasma fragments in these cases. In an index case multiregional sequencing of the primary tumor identified different copy number changes in each sector, suggesting multifocal disease. Our plasma analyses of this index case, performed 13 years after resection of the primary tumor, revealed novel chromosomal rearrangements, which were stable in serial plasma analyses over a 9-month period, which is consistent with the presence of one metastatic clone.

Conclusions: The genomic landscape of prostate cancer can be established by non-invasive means from plasma DNA. Our approach provides specific genomic signatures within 2 days which may therefore serve as 'liquid biopsy'.
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http://dx.doi.org/10.1186/gm434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707016PMC
May 2014

Relationship between prostate cancer gene 3 (PCA3) and characteristics of tumor aggressiveness.

Prostate 2013 Jan 10;73(2):203-10. Epub 2012 Jul 10.

Department of Urology, Medical University of Graz, Graz, Austria.

Background: Data supporting prostate cancer gene 3 (PCA3) as prognostic marker are still inconsistent. With special emphasis to Gleason pattern specific tumor volumes (TVs) the relationships between PCA3 score and different characteristics of tumor aggressiveness were meticulously analyzed.

Methods: In 127 patients treated with radical prostatectomy for clinically localized prostate cancer, urinary PCA3 score was quantified using Progensa™ PCA3 assay. Total TV and Gleason patterns' specific tumor volumes (GPTV) were assessed by computer-assisted planimetry. Spearman's rank correlations coefficients (r) were calculated to assess relationships between PCA3 and TV as well as GPTV. Regression analyses were performed to estimate the relationship between PCA3 and TV as well as non-organ confined disease.

Results: Mean patients' age was 60.8 years. Patients showed a mean PSA level of 8.1 ng/ml and a mean PCA3 score of 68.5. PCA3 was not significantly correlated with TV (r = 0.131, P = 0.142). Stratified by Gleason score groups ≤ 6, 7, and ≥ 8, PCA3 showed no significant correlations with TV. In a subgroup analysis of 50 patients with different primary and secondary Gleason patterns there was neither a correlation with the primary GPTV (r = 0.071, P = 0.626) nor with the secondary GPTV (r = 0.052, P = 0.722). The PCA3 score was neither an independent predictor for TV nor for non-organ confined disease.

Conclusions: The PCA3 score did not show any significant correlation with TV, primary or secondary GPTV. Moreover, the PCA3 score was not an independent predictor for TV or for non-organ confined disease. Thus, the PCA3 score had no impact for the prediction of aggressive prostate cancers.
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http://dx.doi.org/10.1002/pros.22558DOI Listing
January 2013

A case of descending colon carcinoma metastasized to left spermatic cord, testis, and epididymis.

Cent European J Urol 2012 12;65(2):94-5. Epub 2012 Jun 12.

Department of Urology, Medical University Graz, Austria.

We report a case of descending colon carcinoma metastasized to the left spermatic cord, testis, and epididymis. A 77-year old male patient underwent a left hemicolectomy for a descending colon cancer. He was referred to our department because of swelling and pain of the left scrotum two years and six months after surgery. High left orchiectomy was performed. Histological examination revealed a metastasis of the colon carcinoma within the spermatic cord and epididymis approaching the testicle. Reports on metastatic cancer of the testis are scarce, because this metastatic cancer is extremely rare. In general, testicular pain is rare in the elderly. We suggest that any elder presenting with testicular pain deserves a complete clinical and diagnostic evaluation.
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http://dx.doi.org/10.5173/ceju.2012.02.art10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921781PMC
February 2014

Prostate cancers detected by saturation repeat biopsy impairs the Partin tables' accuracy to predict final pathological stage.

BJU Int 2012 Aug 17;110(3):363-8. Epub 2011 Nov 17.

Department of Urology, Medical University of Graz, Graz, Austria.

Objective: • To analyse the overall accuracy of Partin tables, with special emphasis to potential limitations resulting from differences between prostate cancers detected by different biopsy schedules.

Patients And Methods: • Clinical characteristics from 599 patients treated with radical prostatectomy defined the 2007 Partin probabilities of organ confinement (OC), seminal vesicle invasion (SVI) and extracapsular extension (ECE). Prostate cancers were detected by initial biopsy (IBx) with ≤12 cores in 405 patients (67.6%), by conventional repeat biopsy (CRBx) with ≤12 cores in 99 (16.5%) and by saturation repeat biopsy (SRBx) with ≥20 cores in 95 patients (15.9%). • The area under the curve (AUC) estimated by the receiver operating characteristic curve, assessed the predictive accuracy of the 2007 Partin tables.

Results: • The Partin tables AUC of the IBx, CRBx and the SRBx groups were 0.730 vs 0.701 vs 0.585 for OC, 0.631 vs 0.689 vs 0.547 for ECE, and 0.775 vs 0.755 vs 0.641 for SVI, respectively.

Conclusions: • The overall accuracy of the 2007 Partin tables was clearly inferior in patients with prostate cancers detected by SRBx. • Prostate cancers detected by SRBx undermine the Partin tables' overall accuracy, and this group of patients may be miscounselled by vague predictions.
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http://dx.doi.org/10.1111/j.1464-410X.2011.10765.xDOI Listing
August 2012

A comparative performance analysis of total prostate-specific antigen, percentage free prostate-specific antigen, prostate-specific antigen velocity and urinary prostate cancer gene 3 in the first, second and third repeat prostate biopsy.

BJU Int 2012 Jun 21;109(11):1627-35. Epub 2011 Sep 21.

Department of Urology Pathology, Medical University Graz, Graz, Austria.

Unlabelled: Study Type - Diagnosis (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Risk factor assessment in the repeat biopsy setting is affected by a decreasing diagnostic accuracy of each single risk factor (e.g. DRE, tPSA, %fPSA, complexed PSA, PSA density or PSAV] with increasing number of prostate biopsy sessions. PCA3 shows impressive diagnostic performance in the initial and early repeat biopsy settings. In a head-to-head comparison we demonstrate the concept that the number of previous repeat biopsy session strongly influences performance characteristics of biopsy risk factors, including PCA3. While the novel diagnostic marker would have avoided a considerable number of unnecessary biopsies in the first repeat biopsy scenario, its effects dissipated at second and ≥ third repeat biopsies.

Objective: To compare the performance characteristics of prostate cancer risk factors such as total prostate-specific antigen (tPSA), percentage free PSA (%fPSA), PSA velocity (PSAV) and urinary prostate cancer gene 3 (PCA3) at first, second and ≥ third repeat biopsy session.

Patients And Methods: Patients (n= 127) aged ≤70 years, with suspicious digital rectal examination (DRE) and/or persistently elevated age-specific total PSA levels (2.5-6.5 ng/mL) and/or suspicious prior histology (atypical small acinar proliferations [ASAPs]≥ two cores affected by high-grade prostatic intra-epithelial neoplasia [HGPIN]) undergoing either a first, second, or ≥ third repeat biopsy were investigated using a 12- or 24-core biopsy scheme. PSAV (≥ three values collected over ≥12 months) was calculated using the log-slope method. PCA3 scores were assessed using the Progensa assay®. After stratification according to the number of previous biopsies (first, second and ≥ third), calculation of specificity, positive and negative predictive values (PPV, NPV) and the proportion of avoided unnecessary repeat biopsies (PAB) compared with tPSA at fixed sensitivity thresholds (75, 85 and 95%) were performed. Finally, accuracy estimates (area under the curve [AUC]) were quantified for each repeat biopsy scenario.

Results: At repeat biopsy, overall prostate cancer (PCa) detection was 34.6%. At first repeat biopsy, PCA3 predicted PCa best (AUC = 0.80) and would have avoided 72.2% of repeat biopsies (75% sensitivity) compared with tPSA. At second repeat biopsy, %fPSA demonstrated the highest accuracy (AUC = 0.82) and would have avoided 66.7% of repeat biopsies (75% sensitivity) compared with tPSA. At ≥ third repeat biopsy, again %fPSA demonstrated the highest accuracy (AUC = 0.70) and would have avoided 45.0% of repeat biopsies (75% sensitivity) compared with tPSA. The main limitation of our study resides in its small sample size.

Conclusions: The findings of the present study promote the concept that the number of previous repeat biopsy sessions strongly influences the performance characteristics of biopsy risk factors. Total PSA was no significant risk factor in the entire analysis. By contrast, %fPSA performed best at second and ≥ third repeat biopsy. PSAV's diagnostic potential was reserved to patients at second and ≥ third repeat biopsy. Finally, PCA3 demonstrated the highest diagnostic accuracy and potential to reduce unnecessary biopsies at first repeat biopsy. However, this advantage dissipated at second and ≥ third repeat biopsy.
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http://dx.doi.org/10.1111/j.1464-410X.2011.10584.xDOI Listing
June 2012

Critical assessment of preoperative urinary prostate cancer antigen 3 on the accuracy of prostate cancer staging.

Eur Urol 2011 Jan 20;59(1):96-105. Epub 2010 Oct 20.

Department of Urology, Medizinische Universität Graz, Graz, Austria.

Background: Knowledge about the staging significance of the prostate cancer antigen 3 (PCA3) score to better identify pathologic features after radical prostatectomy (RP) is limited and controversial.

Objective: Our aim was to study the clinical staging significance of PCA3 to identify pathologic favorable and/or unfavorable features in the RP specimen.

Design, Setting, And Participants: Complete retrospective clinical and pathologic data of consecutive men who had undergone RP from three tertiary referral centers including preoperative PCA3 scores (n=305) and computer-assisted planimetrically measured tumor volume data (n=160) were available.

Intervention: All patients were treated with RP.

Measurements: PCA3 scores were assessed using the PROGENSA assay (Gen-Probe, San Diego, CA, USA). Beyond standard risk factors (age, digital rectal examination, prostate-specific antigen, prostate volume, biopsy Gleason score, percentage of positive cores), five different PCA3 codings were used in logistic regression models to identify five distinct pathologic end points: (1) low-volume disease (<0.5 ml), (2) insignificant prostate cancer (PCa) according to the Epstein criteria, (3) extracapsular extension (ECE), (4) seminal vesicle invasion (SVI), and (5) aggressive disease defined as Gleason sum ≥7. Accuracy estimates of each end point were quantified using the area under the curve (AUC) of the receiver operator characteristic analysis in models with and without PCA3.

Results And Limitations: PCA3 scores were significantly lower in low-volume disease and insignificant PCa (p ≤ 0.001). AUC of multivariable low-volume disease (+2.4 to +5.5%) and insignificant PCa models (+3 to +3.9%) increased when PCA3 was added to standard clinical risk factors. In contradistinction, regardless of its coding, PCA3 scores were not significantly elevated in pathologically confirmed ECE (p=0.4) or SVI (p=0.5), respectively. Higher PCA3 scores were associated with aggressive disease (p<0.001). Importantly, the addition of PCA3 to multivariable intermediate- and high-grade models did not improve prediction. Despite reporting the largest pathologic PCA3 study, the main limitation resides in its small sample size.

Conclusions: PCA3 was confirmed as a valuable predictor of pathologically confirmed low-volume disease and insignificant PCa. Further exploration of its role as an additional marker to select patients for active surveillance may be warranted. In contradistinction, assessment of pathologically advanced or aggressive PCa is not improved using PCA3.
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http://dx.doi.org/10.1016/j.eururo.2010.10.024DOI Listing
January 2011

Decision curve analysis to compare 3 versions of Partin Tables to predict final pathologic stage.

Urol Oncol 2012 Jul-Aug;30(4):396-401. Epub 2010 Sep 29.

Department of Urology, Medical University of Graz, Graz, Austria.

Objective: To perform a decision curve analysis (DCA) to compare the Partin Tables 1997, 2001, and 2007 for their clinical applicability.

Material And Methods: Clinical and pathologic data of 687 consecutive patients treated with open radical prostatectomy for clinically localized prostate cancer between 2003 and 2008 at a single institution were used. DCA quantified the net benefit relating to specific threshold probabilities of extraprostatic extension (EPE), seminal vesicle involvement (SVI), and lymph node involvement (LNI).

Results: Overall, EPE, SVI, and LNI were recorded in 17.8, 6.0, and 1.2%, respectively. For EPE predictions, the DCA favored the 2007 version vs. 1997 for SVI vs. none of the versions for LNI.

Conclusions: DCA indicate that for very low prevalence conditions such as LNI (1.2%), decision models are not useful. For low prevalence rates such as SVI, the use of different versions of the Partin Tables does not translate into meaningful net gains differences. Finally, for intermediate prevalence conditions such as EPE (18%), despite apparent performance differences, the net benefit differences were also marginal. In consequence, the current analysis could not confirm an important benefit from the use of the Partin Tables and it could not identify a clearly better version of any of the 3 available iterations.
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http://dx.doi.org/10.1016/j.urolonc.2010.07.003DOI Listing
November 2012

Head to head comparison of three generations of Partin tables to predict final pathological stage in clinically localised prostate cancer.

Eur J Cancer 2010 Aug 17;46(12):2235-41. Epub 2010 May 17.

Department of Urology, Medical University of Graz, Graz, Austria.

Objective: To perform a head to head comparison between three generations of Partin tables, namely from 1997, 2001 and the last updated version of 2007.

Material And Methods: The external validations were based on clinical and pathological data of 687 consecutive patients undergoing radical prostatectomy for clinically localised prostate cancer between 2003 and 2008. Three versions of the Partin tables were compared for their accuracy and performance to predict final pathological stage using receiver operating characteristic (ROC) curve and Loess plots analyses.

Results: Of the whole cohort, 76.2% of men were presented with organ-confined disease (OC), 17.0% had extraprostatic extension (ECE), 6.0% showed seminal vesicle involvement (SVI) and 1.2% had lymph node involvement (LNI). The area under the receiver operating characteristic curve (AUC) of the Partin Tables 1997, 2001 and 2007 was 0.731, 0.727 and 0.722 for OC; 0.671, 0.662 and 0.650 for ECE; 0.795, 0.788 and 0.779 for SVI as well as 0.826, 0.786 and 0.746 for LNI, respectively.

Conclusion: All three generations of the Partin tables showed a good accuracy to predict OC, SVI and LNI. However, the predictive accuracy for ECE was only modest. Overall, the newer versions of the Partin tables could not exceed the version of 1997 in their predictive accuracy for any pathological stage and they failed to demonstrate a clear advantage. Our results underline the necessity to perform external validations before the implementation of a new predicting tool.
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http://dx.doi.org/10.1016/j.ejca.2010.04.013DOI Listing
August 2010

The use of body mass index to predict pathological stage in patients with clinically localized prostate cancer.

Onkologie 2007 Oct 21;30(10):489-94. Epub 2007 Sep 21.

Department of Urology, Medical University of Graz, Austria.

Background: To investigate whether body mass index (BMI) is an independent risk factor for nonorgan-confined disease in patients with clinically localized prostate cancer.

Patients And Methods: Overall, 735 patients undergoing radical prostatectomy formed the study cohort. Pathological and clinical factors with special emphasis to BMI were used to determine a model for the prediction of nonorgan-confined disease.

Results: 359 patients had pathologically nonorgan-confined prostate cancer. These patients showed a significantly higher BMI than those with organ-confined disease (26.7 vs. 26.2; p = 0.0012). In multivariate analysis, age (p = 0.049), prostate-specific antigen (PSA) (p < 0.001), clinical stage (p < 0.001), prostatectomy grade (p < 0.001), and BMI (p = 0.004) were independent risk factors for nonorgan-confined disease. In patients with a serum PSA between 10.1 and 20 ng/ml only prostatectomy grade (p < 0.001) and BMI (p = 0.005) remained independent predictors.

Conclusion: Patients with nonorgan-confined disease showed a significantly higher BMI than those with organ-confined stages. Moreover, BMI was an independent predictor for nonorganconfined prostate cancer. This knowledge might be helpful in patient counseling to choose between various options for the treatment of clinically localized prostate cancer.
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http://dx.doi.org/10.1159/000106096DOI Listing
October 2007

Obesity and prostate cancer: an ambiguous relationship.

Authors:
Herbert Augustin

Eur J Cancer 2007 May 2;43(7):1114-6. Epub 2007 Apr 2.

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http://dx.doi.org/10.1016/j.ejca.2007.03.006DOI Listing
May 2007

Prediction of stone-free rate after ESWL.

Authors:
Herbert Augustin

Eur Urol 2007 Aug 26;52(2):318-20. Epub 2007 Mar 26.

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http://dx.doi.org/10.1016/j.eururo.2007.03.059DOI Listing
August 2007

Shift of tumor features in patients with clinically localized prostate cancer undergoing radical prostatectomy since the beginning of the PSA era.

Wien Klin Wochenschr 2006 Jun;118(11-12):348-54

Department of Urology, Medical University of Graz, Graz, Austria.

Aim: To analyze trends of clinical and tumor characteristics over a 12-year period since the beginning of the prostate-specific antigen (PSA) era in a consecutive series of radical prostatectomies.

Patients And Methods: Between 1993 and 2004 a consecutive series of 1351 patients underwent radical prostatectomy for clinically localized prostate cancer (PC) in a single institution. Clinical and histopathological information was entered into our computer database and analyzed for changes over time.

Results: The annual frequency of surgical interventions increased from 43 to 160 (272%) during the observation period (r = 0.930; p < 0.01). The detection of PC based solely on pathological PSA levels rose impressively from 7% to 70% (r = 0.986; p < 0.01). The rates of organ-confined disease also increased significantly from 47% to 79% (r = 0.774; p < 0.01). Stage pT3a decreased somewhat from 28% to 18% (r = -0.389; n.s.) whereas pT3b decreased significantly from 26% to 3% (r = -0.729; p < 0.01).

Conclusion: During the 12-year period, PC was increasingly detected on the basis of a pathological PSA level only and shifted significantly to more organ-confined stages. With a time delay, these findings are consistent with trends observed in large centers in the USA.
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http://dx.doi.org/10.1007/s00508-006-0608-zDOI Listing
June 2006

Prostate cancers in the transition zone: Part 1; pathological aspects.

BJU Int 2004 Dec;94(9):1221-5

Institute of Pathology, University of Hamburg, Hamburg, Germany.

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http://dx.doi.org/10.1111/j.1464-410X.2004.05146.xDOI Listing
December 2004

Comparison of accuracy between the Partin tables of 1997 and 2001 to predict final pathological stage in clinically localized prostate cancer.

J Urol 2004 Jan;171(1):177-81

Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

Purpose: We validated externally the predictive accuracy of the 2001 Partin tables and compared the 1997 and 2001 versions.

Materials And Methods: We used ROC derived AUC to test the predictive accuracy of organ confinement (OC), extraprostatic extension (ECE), seminal vesicle invasion (SVI) and lymph node involvement (LNI) of 1997 and 2001 Partin tables derived probabilities. These probabilities were defined by the pretreatment clinical stage, serum prostate specific antigen and biopsy Gleason grade of 2,139 patients treated with radical prostatectomy for clinically localized prostate cancer.

Results: OC, ECE, SVI and LNI were noted in 63.5%, 23.1%, 10.5% and 2.9% of cases, respectively. AUC of the 2001 tables was 0.787, 0.766, 0.775 and 0.790, for OC, ECE, SVI and LNI, respectively. These values were virtually the same as the respective 1997 Partin table AUC values, namely 0.784, 0.728, 0.791 and 0.799.

Conclusions: This external validation of the 2001 Partin tables confirms good predictive accuracy of the updated tables. However, predictive accuracy in this external validation data set of 2,139 European men is virtually the same as that of the original 1997 tables. Therefore, a transition from the 1997 tables to the updated 2001 version does not appear warranted unless superior accuracy is demonstrated in other external cohorts.
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http://dx.doi.org/10.1097/01.ju.0000099827.77355.a7DOI Listing
January 2004

Characterisation of biomolecular profiles in primary high-grade prostate cancer treated by radical prostatectomy.

J Cancer Res Clin Oncol 2003 Nov 26;129(11):662-8. Epub 2003 Sep 26.

Department of Urology, Karl-Franzens-University Graz, Auenbruggerplatz 7, 8036 Graz, Austria.

Purpose: The aim of this study was to compare the biomolecular profile of high-grade (HG) with low-grade (LG) prostate cancers matched by preoperative serum prostate-specific antigen (PSA) levels.

Methods: From 2,560 patients undergoing radical prostatectomy for localised disease, 24 men with HG cancer (Gleason score > or =9) were eligible. Their clinical data were compared with those of 24 LG tumours (Gleason score < or =6), matched by PSA values. The expression of Ki-67, p53, Bcl-2, chromogranin A, alpha-catenin, and PSA were analysed and compared between both groups.

Results: The expression of Ki-67 (P=0.031), p53 (P=0.008), Bcl-2 (P=0.002), and chromogranin A (P=0.042) were expressed significantly higher, and alpha-catenin (P=0.020) and PSA (P<0.001) significantly lower in HG tumours. Cancer volumes of HG and LG differed significantly (10.6 cm3 vs 5.3 cm3; P=0.006). Overall, cancer volume correlated with increased expression of p53 (r=0.52; P<0.001) and chromogranin A (r=0.46; P<0.001), and with decreased expression of PSA (r=0.41; P<0.004).

Conclusions: According to our data, tumour grade is clearly associated with a change in the biomolecular profile, even between patients with similar serum PSA levels. As the prognosis of HG prostate cancer is poor, these tumours should be analysed by immunohistochemical staining to identify specific tumour features for an appropriate selection of adjuvant therapy.
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http://dx.doi.org/10.1007/s00432-003-0496-9DOI Listing
November 2003

Prognostic significance of visible lesions on transrectal ultrasound in impalpable prostate cancers: implications for staging.

J Clin Oncol 2003 Aug;21(15):2860-8

Department of Urology, University of Hamburg, Hamburg, Germany.

Purpose: The current tumor-node metastasis (TNM) staging system classifies impalpable prostate cancers identified by needle biopsy and invisible by imaging as T1c and those visible as T2. Palpable cancers are classified as at least T2. However, most urologists consider impalpable prostate cancers T1c tumors, irrespective of findings on transrectal ultrasound (TRUS). The aim of this article is to provide a differentiated view of the significance of TRUS findings for staging purposes in impalpable prostate cancers.

Patients And Methods: A consecutive series of 1670 patients with impalpable tumors and palpable T2 cancers after radical prostatectomy were evaluated. Tumor characteristics and 5-year biochemical cure rates of cancers invisible and visible on TRUS were compared, as well as the rates of impalpable but visible and palpable T2 cancers.

Results: Impalpable cancers invisible on TRUS presented significantly more favorable pathologic stages and lower cancer volumes than those visible on TRUS (P =.002, P =.010). In the latter, these clinical features were more favorable compared with T2 cancers (P <.001, P <.001). Progression-free probability of impalpable cancers invisible on TRUS was 86.8%; progression-free probability for impalpable cancers visible on TRUS was 85.4% (log-rank test P =.2060). The corresponding rate for T2 tumors was 73.9%, significantly lower when compared to those of visible and impalpable cancers (log-rank test P =.0001).

Conclusion: Impalpable prostate cancers invisible on TRUS present more favorable cancer features than those that are visible on TRUS. However, these differences are not as pronounced as those between impalpable but visible cancers and palpable T2 tumors. Thus, based on our data, it seems inappropriate to classify impalpable prostate cancers visible on TRUS as T2 cancers.
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http://dx.doi.org/10.1200/JCO.2003.11.130DOI Listing
August 2003

Zonal location of prostate cancer: significance for disease-free survival after radical prostatectomy?

Urology 2003 Jul;62(1):79-85

Department of Urology, University Hospital Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.

Objectives: To analyze the zonal location of prostate cancer as a possible predictive feature of progression-free survival after radical prostatectomy.

Methods: Prostate cancers were divided into three groups according to the percentage of cancer volume (70% or more, 31% to 69%, and 30% or less) located in the transition zone (TZ). In a total of 307 patients, 5-year progression-free probabilities were estimated for different clinical and pathologic tumor characteristics using the Kaplan-Meier method. With emphasis on the percentage of cancer volume located in the TZ, univariate and multivariate analyses were performed to calculate their prognostic significance in predicting progression-free probability.

Results: Prostate cancer with 70% or more, 31% to 69%, and 30% or less of the cancer volume in the TZ was found in 17.3%, 6.8%, and 75.9% of the patients, respectively. Patients with tumors with 70% or more of the cancer volume in the TZ had a significantly (log-rank P = 0.0402) greater rate of biochemical cure than those with 30% or less (82.1% versus 66.2%). The increasing percentage of cancer volume located in the TZ was significantly (P = 0.0258) associated with a greater progression-free probability in univariate analysis, but did not retain independent significance (P = 0.5748) in multivariate analysis. Instead, pathologic stage (P <0.0001), lymph node involvement (P = 0.0189), and Gleason score on prostatectomy specimen (P = 0.0023) were independent prognosticators.

Conclusions: The location of prostate cancer in the TZ was associated with a greater overall biochemical cure rate after radical prostatectomy. However, it was not an independent prognosticator on multivariate analysis. Therefore, the knowledge about zonal location of prostate cancer offers no advantage over the well-established prognostic factors in predicting disease recurrence.
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http://dx.doi.org/10.1016/s0090-4295(03)00248-6DOI Listing
July 2003

Insignificant prostate cancer in radical prostatectomy specimen: time trends and preoperative prediction.

Eur Urol 2003 May;43(5):455-60

Department of Urology, University Hospital Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.

Objectives: We analysed systematically a consecutive series of radical prostatectomy specimens performed between January 1992 and June 2002 with emphasis to time trends, tumour characteristics and preoperative prediction of insignificant prostate cancers (cancer volume < or =0.5 cm(3) and Gleason pattern < or =6).

Methods: In a total of 1254 patients, prostate cancers (PC) were divided by a cancer volume of 0.5 cm(3). The two groups were compared in their clinical and pathological tumour characteristics. Correlation was determined between yearly incidence rates of T1c and insignificant PC. Furthermore, a logistic regression analysis was performed to calculate the ability to predict insignificant PC and a statistical model was established.

Results: Overall, 73 (5.8%) of 1254 men presented with insignificant PC. The incidence of insignificant PC showed no significant linear correlation with that of T1c PC (p<0.61). PSA density and percentage of cancer per biopsy set were assessed as independent prognosticators predicting insignificant PC. Using a threshold of 1% of cancer per biopsy set and a PSA density < or =0.10, positive and negative predictive values were 45.0% and 93.3%, respectively.

Conclusion: In our series, only few men undergoing radical prostatectomy were affected by insignificant PC. Their incidence showed no statistically significant correlation with that of T1c tumours. Furthermore, insignificant PC was predictable by PSA density and percentage of cancer per biopsy set. Mainly elderly patients facing different treatment options for localized PC may benefit from this information.
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http://dx.doi.org/10.1016/s0302-2838(03)00139-8DOI Listing
May 2003
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