Benefit and harm of lymphadenectomy in intermediate risk prostate cancer: comparison of five nomograms.

BACKGROUND: Pelvic lymph node dissection (PLND) is recommended method for detecting prostate cancer (PCa) nodal metastases although associated with serious complications. In this study, we aimed to assess benefit/harm of routine PLND in intermediate risk PCa patients and to compare diagnostic yield of five different nomograms in predicting lymph node invasion (LNI). METHODS: Retrospective analysis of consecutive PCa patients with intermediate risk of biochemical recurrence who underwent open radical prostatectomy (RP) with bilateral PLND between January 2017 and December 2019 at our institution. Partin, 2012-Briganti, 2018-Briganti, Cagiannos and Memorial Sloan Kettering Cancer Center (MSKCC) values were calculated. To compare accuracy, sensitivity, specificity, and area under receiver-operating curve (AUC) were calculated and then optimal cutoff values were estimated, analyses repeated and compared. To assess benefit and harm of PLND, relative risk (RR) and number need to treat (NNT) with LNI and complications set as outcome were calculated. RESULTS: Total 309 subjects. Average age 62.2 years, average PSA 7.2 ng/mL; 18 (5.8%) had LNI; 88 (28.5%) suffered Clavien-Dindo grade 3-5 complication. AUC for predicting LNI: 0.729 for 2012-Briganti, 0.660 for MSKCC, 0.521 for 2018-Briganti, 0.486 for Cagiannos, and 0.424 for Partin. None of pairwise AUC comparisons based on default and newly established cutoff values were statistically significant. Lowest NNT was for Partin and Cagiannos with default cutoff (≥ 5%). Risks of serious complications between higher/lower than cutoff values were non-significant across nomograms. CONCLUSIONS: 2012-Briganti nomogram outperforms, although not significantly, MSKCC, 2018-Briganti, Cagiannos, and Partin nomograms in classifying LNI in intermediate risk PCa patients. Routine PLND in these patients should be avoided, due to high rate and severity of complications.

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

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.

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

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.

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

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.

Innovations in diagnostic imaging of localized prostate cancer.

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.

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

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.

Charlson-Deyo Comorbidity Index as a Novel Predictor for Recurrence in Non-Muscle-Invasive Bladder Cancer.

PURPOSE: To test the association between the Charlson-Deyo Comorbidity Index (CCI) and the recurrence of non-muscle-invasive bladder cancer (NMIBC). METHODS: NMIBC (Ta, T1, TIS) patients who underwent transurethral resection of bladder tumor (TURB) between 2010 and 2018 were identified within a retrospective data repository of a large university hospital. Kaplan-Meier estimates and uni- and multivariable Cox regression models tested for differences in risk of recurrence according to low vs. high comorbidity burden (CCI ≤ 4 vs. >4) and continuously coded CCI. RESULTS: A total of 1072 NMIBC patients were identified. The median follow-up time of the study population was 55 months (IQR 29.6-79.0). Of all 1072 NMIBC patients, 423 (39%) harbored a low comorbidity burden vs. 649 (61%) with a high comorbidity burden. Overall, the rate of recurrence was 10% at the 12-month follow-up vs. 22% at the 72-month follow-up. In low vs. high comorbidity burden groups, rates of recurrence were 6 vs. 12% at 12 months and 18 vs. 25% at 72 months of follow-up (p = 0.02). After multivariable adjustment, a high comorbidity burden (CCI > 4) independently predicted a higher risk of recurrence (HR 1.42, 95% confidence interval (CI) 1.06-1.92, p = 0.018). After multivariable adjustment, the hazard of recurrence increased by 5% per each one-unit increase on the CCI scale (HR 1.05, 95% CI 1.00-1.10, p = 0.04). CONCLUSIONS: Comorbidities in NMIBC patients are common. Our data suggest that patients with higher CCI have an increased risk of BC recurrence. As a consequence, patients with a high comorbidity burden should be particularly encouraged to adhere to NMIBC guidelines and conform to follow-up protocols.

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

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.

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.

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.

Combining targeted and systematic prostate biopsy improves prostate cancer detection and correlation with the whole mount histopathology in biopsy naïve and previous negative biopsy patients.

Objective: Guidelines for previous negative biopsy (PNB) cohorts with a suspicion of prostate cancer (PCa) after positive multiparametric (mp) magnetic-resonance-imaging (MRI) often favour the fusion-guided targeted prostate-biopsy (TB) only approach for Prostate Imaging-Reporting and Data System (PI-RADS) ≥3 lesions. However, recommendations lack direct biopsy performance comparison within biopsy naïve (BN) vs. PNB patients and its prognostication of the whole mount pathology report (WMPR), respectively. We suppose, that the combination of TB and concomitant TRUS-systematic biopsy (SB) improves the PCa detection rate of PI-RADS 2, 3, 4 or 5 lesions and the International Society of Urological Pathology (ISUP)-grade predictability of the WMPR in BN- and PNB patients. Methods: Patients with suspicious mpMRI, elevated prostate-specific-antigen and/or abnormal digital rectal examination were included. All PI-RADS reports were intramurally reviewed for biopsy planning. We compared the PI-RADS score substratified TB, SB or combined approach (TB/SB) associated BN- and PNB-PCa detection rate. Furthermore, we assessed the ISUP-grade variability between biopsy cores and the WMPR. Results: According to BN (n = 499) vs. PNB (n = 314) patients, clinically significant (cs) PCa was detected more frequently by the TB/SB approach (62 vs. 43%) than with the TB (54 vs. 34%) or SB (57 vs. 34%) (all p < 0.0001) alone. Furthermore, we observed that the TB/SB strategy detects a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports, both in BN and PNB men. In contrast, applied biopsy techniques were equally effective to detect csPCa within PI-RADS 2 lesions. In case of csPCa diagnosis the TB approach was more often false-negative in PNB patients (BN 11% vs. PNB 19%; p = 0.02). The TB/SB technique showed in general significantly less upgrading, whereas a higher agreement was only observed for the total and BN patient cohort. Conclusion: Despite csPCa is more frequently found in BN patients, the TB/SB method always detected a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports of our BN and PNB group. The TB/SB strategy predicts the ISUP-grade best in the total and BN cohort and in general shows the lowest upgrading rates, emphasizing its value not only in BN but also PNB patients.

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

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.

Seasonal Variations in the Diagnosis of Testicular Germ Cell Tumors: A National Cancer Registry Study in 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 (p < 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 (p < 0.001). Focusing on seasonality, the incidence during the months of Oct-Dec (p = 0.008) and Jan-Mar (p < 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 (p < 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.

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

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.

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

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.

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

Introduction. To analyze the impact of radical prostatectomy (RPE) on erectile function and lower urinary tract function in comparison to age-matched healthy men. Materials and Methods. Patients who underwent radical retropubic prostatectomy completed questionnaires containing the IIEF-5, the Bristol female LUTS questionnaire, and the International Prostate Symptom Score (IPSS). Results. Patients after RPE were included (n = 363). Age-matched healthy men (n = 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. Conclusions. 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.

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

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.

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

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.

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

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.

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

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.

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

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.