Holmium laser enucleation of the prostate is safe in patients with prostate cancer and lower urinary tract symptoms--a retrospective feasibility study.

OBJECTIVE: To evaluate the outcome of holmium laser enucleation of the prostate (HoLEP) in the known presence of prostate cancer (PCa) and concomitant lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: We retrospectively identified 62 patients who underwent HoLEP for LUTS in the known presence of PCa at our center. Perioperative data were assessed including complications, functional outcomes, and quality of life (QoL). Giving respect to different disease characteristics, patients were stratified according to treatment strategy setting into palliative (I), radiation (II), and surveillance (III) groups and compared accordingly. RESULTS: Median follow-up (FU) of the entire study cohort was 27 months (range 2-65 mos). Medians of functional parameters (International Prostate Symptom Score): 18.5 vs 4.5, QoL: 4 vs 1, maximal flow rate: 9.0 vs 18.8 mL/s and residual urine: 100 vs 0 mL, all P<0.05) improved significantly in all groups. Perioperative complications were low and without any statistically significant difference between the groups. Postoperatively, voiding was successful in 90.3% of all patients; at last FU, 17% had some degree of urinary incontinence. Treatment strategy groups showed comparable functional outcomes after HoLEP. CONCLUSION: In the presence of PCa and LUTS, HoLEP represents a feasible, safe, and effective treatment option for patients unfit or without indication for radical prostatectomy. This applies as well in a palliative situation of advanced, obstructive PCa as for patients with LUTS who are scheduled for radiation therapy or surveillance in presumably indolent disease.

Epithelial cell adhesion molecule is an independent prognostic marker in clear cell renal carcinoma.

Epithelial cell adhesion molecule (EPCAM) has recently attained a renewed interest as a candidate protein in diagnosis, prognostication and therapy of various tumor entities. The molecular epidemiology and prognostic relevance of EPCAM in renal cell carcinoma (RCC) and amongst the histological subtypes of RCC are unclear. We analyzed the prevalence and prognostic significance of EPCAM in a tumor tissue microarray composed of 1,088 independent RCCs samples by immunohistochemistry (IHC). We found significant variations of EPCAM IHC staining intensities in between the RCC subtypes: in papillary and chromophobe RCC, the majority of tumors (89-93%) showed an at least weak EPCAM protein expression. In the largest subgroup, the clear cell (cc)RCC (n = 767), a negative EPCAM IHC was found in 1/3 of the patients and was associated with high-grade disease and nodal metastases. Kaplan-Meier analyses demonstrated a significant association between positive EPCAM IHC and prolonged overall survival, even in a subset of low-risk ccRCC. In multivariable analyses, EPCAM represented an independent risk factor of survival throughout all subgroups. For localized, low-grade ccRCC, information of EPCAM IHC raised predictive accuracy of a multivariate model by ∼5%, compared to T-stage and grade alone. Our findings indicate that EPCAM is an independent prognostic molecular marker in ccRCC and, especially in localized ccRCC, might be able to provide auxiliary information for a better prognostication.

Prognostic value of alpha-methyl CoA racemase (AMACR) expression in renal cell carcinoma.

PURPOSE: Alpha-methyl CoA racemase (AMACR) is used as an immunohistochemical marker for renal cell carcinoma (RCC) subtyping to distinguish papillary (pap) RCC. Expression of AMACR in other renal tumor subtypes is inhomogeneous, and the clinical and prognostic value of AMACR is unknown. The aim of this study was to asses AMACR protein expression in different RCC subtypes and to investigate its prognostic significance. METHODS: Protein expression of AMACR was analyzed in 1,088 renal tumor samples, among them 809 clear cell RCC and 151 papRCC, by immunohistochemistry using tissue microarry (TMA) technique. Results were correlated with clinicopathological data and to follow-up data [overall (OS)/cancer-specific survival (CSS)]. RESULTS: Frequency of AMACR expression was significantly higher in papRCC compared to other tumor subtypes (83% vs. 15-35%, p < 0.0001). Presence of AMACR did not correlate with stage or nodal metastases in papRCC. In a dichotomized scoring (negative vs. positive expression), an inverse correlation between higher grade (p = 0.03) and presence of distant metastasis (p = 0.014) was observed in papRCC. AMACR expression correlated with the presence of nodal metastasis in ccRCC (p = 0.02). Both in ccRCC and in papRCC, OS and CSS did not correlate with the AMACR expression status. CONCLUSIONS: The high expression in papRCC confirms AMACR to be a marker for subtype differentiation in RCC, while a missing expression in this subtype seems to be associated with negative pathological features. However, in contrast to other tumor entities, AMACR expression seems to have a limited prognostic impact in renal carcinoma, especially with regard to survival.

A critical analysis of the actual role of minimally invasive surgery and active surveillance for kidney cancer.

CONTEXT: The incidence of renal cell carcinomas (RCCs) has increased steadily-most rapidly for small renal masses (SRMs). Paralleling the changing face of RCC in the past 2 decades, new, less invasive surgical options have been developed. Laparoscopic radical nephrectomy (LRN) is an established procedure for the treatment of RCC. Treatment of SRMs includes open partial nephrectomy (OPN), laparoscopic partial nephrectomy (LPN), thermal ablation, and active surveillance. OBJECTIVE: To present an overview of minimally invasive treatment options and data on surveillance for kidney cancer. EVIDENCE ACQUISITION: Literature and meeting abstracts were searched using the terms renal cell carcinoma, minimally invasive surgery, laparoscopic surgery, thermal ablation, surveillance, and robotic surgery. The articles with the highest level of evidence were identified with the consensus of all the collaborative authors and reviewed. EVIDENCE SYNTHESIS: Renal insufficiency, as measured by the glomerular filtration rate, occurs more often after radical nephrectomy than partial nephrectomy (PN). OPN and LPN show comparable results in long-term oncologic outcomes. The treatment modality for SRMs should therefore be nephron-sparing surgery (NSS). In select patients, thermal ablation or active surveillance of SRMs is an alternative. CONCLUSIONS: LRN has become the standard of care for most organ-confined tumours not amenable to NSS. Amongst NSS options, PN is the treatment of choice, yet remains underutilised in the community. Initial data during its learning curve revealed that LPN had higher urologic morbidity. However, current emerging data indicate that in experienced hands, LPN has shorter ischaemia times, a lower complication rate, and equivalent long-term oncologic and renal functional outcomes, yet with decreased patient morbidity compared to OPN. Robotic partial nephrectomy is being explored at select centres, and cryotherapy and radiofrequency ablation are options for carefully selected tumours. Active surveillance is an option for selected high-risk patients. Percutaneous needle biopsy is likely to gain increasing relevance in the management of small renal tumours.

Unilateral prostate cancer cannot be accurately predicted in low-risk patients.

PURPOSE: Hemiablative therapy (HAT) is increasing in popularity for treatment of patients with low-risk prostate cancer (PCa). The validity of this therapeutic modality, which exclusively treats PCa within a single prostate lobe, rests on accurate staging. We tested the accuracy of unilaterally unremarkable biopsy findings in cases of low-risk PCa patients who are potential candidates for HAT. METHODS AND MATERIALS: The study population consisted of 243 men with clinical stage

Differences in histopathological and biochemical outcomes in patients with low Gleason score prostate cancer.

STUDY TYPE: Diagnosis (case series). LEVEL OF EVIDENCE: 4. OBJECTIVE: To test whether the number or percentage of positive biopsy cores can be used to discriminate between patients with prostate cancer of a favourable and less favourable Gleason score (GS) < or =3 + 3, as prognostically, not all GS 3 + 3 prostate cancers are the same. PATIENTS AND METHODS: In all, 1106 consecutive patients with a prostate-specific antigen (PSA) level of < or =10 ng/mL and a biopsy GS of < or =3 + 3 or 3 + 4 had an open radical prostatectomy. The number of positive biopsy cores (< or =2 vs > or =3) were stratified into low- vs high-risk groups. Subsequently, we stratified patients according to the GS and the percentage of positive biopsy cores (<50% vs > or =50%). The pathological stage and the 5-year biochemical recurrence (BCR)-free survival rates were examined in univariable and multivariable models. RESULTS: Based on the number of positive cores, the rate of extraprostatic disease was 11.7% and 23.3%, respectively, in the low-and high-risk GS < or =3 + 3 groups (P < 0.001). The 5-year BCR-free survival rates were 95.0%, 77.8%, 81.2% and 66.5% for, respectively, low- and high-risk GS < or =3 + 3 and for low- and high-risk GS 3 + 4 patients. Univariable and multivariable intergroup BCR rate differences were statistically significant between low- vs high-risk GS 3 + 3 patients (P < 0.001), but not significant between high-risk GS < or =3 + 3 vs low-risk GS 3 + 4 patients (P = 0.6). Comparable results were obtained when comparisons were made according to the percentage of positive biopsy cores. CONCLUSIONS: Our results corroborate the finding that not all patients with a biopsy GS of < or =3 + 3 prostate cancer have low-risk disease. High-risk GS < or =3 + 3 patients have a similar risk profile as more favourable GS 3 + 4 patients. This finding warrants consideration when deciding on treatment.

External validation of a preoperative nomogram for prediction of the risk of recurrence after radical prostatectomy.

PURPOSE: To test the validity of an updated version of the preoperative Kattan nomogram for prediction of recurrence after radical prostatectomy (RP), published by Stephenson et al. METHODS AND MATERIALS: We relied on clinical and postoperative prostate-specific antigen follow-up data of 1978 patients treated with open RP at our institution between 1992 and 2006. The accuracy of the nomogram-derived recurrence-free survival predictions were separately tested at 1 to 10 years after RP. Moreover, the relationship between the nomogram-predicted recurrence-free survival rate and the observed recurrence-free survival rate was graphically explored in calibration plots. RESULTS: Median follow-up of censored patients was 32 months. For nomogram-derived recurrence-free survival predictions at 1 to 10 years, the accuracy of the nomogram ranged from 70% to 76%. The calibration between the predicted and observed recurrence-free survival rates was good at 1 and 2 years after RP. However, at all other examined time points, departures from ideal predictions were recorded. CONCLUSIONS: Our findings indicate that the preoperative biochemical recurrence nomogram reported by Stephenson et al. can be applied to European patients with good accuracy. However, its calibration was only suboptimal for predictions made 3 or more years after RP, with a tendency to overestimate the probability of recurrence-free survival. This potential limitation should be considered when this tool is applied to European patients.

Sequential use of the tyrosine kinase inhibitors sorafenib and sunitinib in metastatic renal cell carcinoma: a retrospective outcome analysis.

BACKGROUND: To date, few data are available about the sequential use of the tyrosine kinase inhibitors (TKI) sorafenib and sunitinib in metastatic renal cell carcinoma (mRCC). OBJECTIVE: To investigate the effectiveness of the use of sunitinib after progression under sorafenib in mRCC. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of 30 patients with progressive mRCC, treated with sorafenib between May 2005 and February 2008. When radiologic progression was diagnosed, treatment was switched to sunitinib and continued until a further tumour progression occurred. MEASUREMENTS: Radiologic evaluation of the treatment results was performed every 3 mo according to the criteria for Response Evaluation Criteria in Solid Tumors (RECIST). Adverse effects and therapeutic abnormalities (eg, dose reduction) were documented during regular visits. RESULTS AND LIMITATIONS: Of the patients, 50% benefited from the secondary use of sunitinib. In detail, a radiologically confirmed new disease stabilisation or partial response was observed in seven and eight patients, respectively. Median progression-free survival was 8.7 mo and 10.3 mo under sorafenib and sunitinib, respectively. Overall, the median time from the initialisation of the first TKI until progression under therapy with the second TKI was 17.3 mo. To our knowledge, this is the second largest study reporting results of sequential therapy from sorafenib followed by sunitinib. However, the number of patients is still not extensive enough to settle this important question conclusively. CONCLUSIONS: This study supports the hypothesis that sequential TKI therapy with the sorafenib followed by sunitinib has clinical validity in some patients with advanced renal cell carcinoma when progressive disease occurs under the initial TKI therapy.

A nomogram is more accurate than a regression tree in predicting lymph node invasion in prostate cancer.

OBJECTIVE: To compare the performance and discriminant properties of two instruments (a tree-structured regression model and a logistic regression-based nomogram), recently developed to predict lymph node invasion (LNI) at radical prostatectomy (RP), in a contemporary cohort of European patients. PATIENTS AND METHODS: The cohort comprised 1525 consecutive men treated with RP and bilateral pelvic LN dissection (PLND) in two tertiary academic centres in Europe. Clinical stage, pretreatment prostate-specific antigen (PSA) level and biopsy Gleason sum were used to test the ability of the regression tree and the nomogram to predict LNI. Accuracy was quantified by the area under the receiver operating characteristic curve (AUC). All analyses were repeated for each participating institution. RESULTS: The AUC for the nomogram was 81%, vs 77% for the regression tree (P = 0.007). When data were stratified according to institution, the nomogram invariably had a higher AUC than the regression tree (Hamburg cohort: nomogram 82.1% vs regression tree 77.0%, P = 0.002; Milan cohort: 82.4% vs 75.9%, respectively; P = 0.03). CONCLUSIONS: Nomogram-based predictions of LNI were more accurate than those derived from a regression tree; therefore, we recommend the use of nomogram-derived predictions.

Evaluation of renal growth by magnetic resonance imaging and computerized tomography volumes.

PURPOSE: Magnetic resonance imaging (MRI) and computerized tomography (CT) are commonly used to image complex medical conditions but limited data have been reported concerning normal renal volumetric measurement with these imaging techniques. We examined whether normative renal growth curves could be constructed from data derived from these imaging modalities, and from these curves assessed normal and abnormal renal development. MATERIALS AND METHODS: Patients who had undergone prior renal MRI or CT were identified. Total renal volume and renal cortical fraction (CF, cortical/total volume) were calculated, and growth curves were derived. To examine the curve utility for abnormal growth assessment, renal ultrasonography of children with reflux nephropathy was examined, and MRI and radionuclide scans were compared. RESULTS: A total of 60 patients 2 months to 39 years old who underwent MRI were included in the growth curve. The CF of the 120 kidneys was 75.8 +/- 4.3% and independent of sex and age. In 19 patients with vesicoureteral reflux 13 kidneys had cortical scarring, and the CF was decreased (p <0.001, 63.65 +/- 5.72%), indicating disproportionate cortical loss. No difference between CF for normal and vesicoureteral reflux unscarred kidneys was found. Differential renal function on radionuclide study correlated highly with MRI renal volume (r = 0.91). CT was performed in 70 children 1 to 15 years old (mean age 7.9) volume correlated with age and renal length, and the left kidney was larger than right kidney on MRI and CT. CONCLUSIONS: Normative renal growth curves can be constructed from CT and MRI derived renal volumes. Cortical fraction is consistent, and sex and age independent. In reflux nephropathy the CF is reduced and renal differential function on nuclear scan correlates with MRI derived differential volume. This concept may be useful for predicting abnormal renal growth and differential function.

Urinary concentration and tissue messenger RNA expression of monocyte chemoattractant protein-1 as an indicator of the degree of hydronephrotic atrophy in partial ureteral obstruction.

PURPOSE: To find a potential prognostic marker of the induction of hydronephrotic atrophy in congenital hydronephrosis we investigated whether the messenger (m)RNA expression and urinary concentration of monocyte chemoattractant protein-1 (MCP-1) correlated with the degree of partial ureteral obstruction, and subsequent hydronephrotic atrophy and interstitial fibrosis. MATERIALS AND METHODS: We created left partial ureteral obstruction in 96 juvenile Wistar rats and complete ureteral obstruction in 18, while 16 underwent sham operation. Depending on excretion of contrast medium into the renal pelvis after 3 days we defined 2 degrees of hydronephrosis. Renal mRNA expression of MCP-1, and renal pelvic and bladder urinary concentrations of MCP-1 were measured after 1, 2 and 3 weeks, and compared with the degree of hydronephrotic atrophy. RESULTS: Grade 1 partial ureteral obstruction resulted in mild histological changes. Grade 2 partial and complete obstruction resulted in significant hydronephrotic atrophy. MCP-1 mRNA expression in the kidney remained unchanged in grade 1 partial obstruction but was moderately increased in grade 2 partial obstruction and clearly over expressed in complete ureteral obstruction. The renal pelvic urinary concentration of MCP-1 was not higher in rats with grade 1 partial obstruction than in sham operated animals but it was significantly increased in those with grade 2 partial and complete obstruction. CONCLUSIONS: mRNA expression and the urinary concentration of MCP-1 correlate with the degree of obstruction and subsequent renal damage in hydronephrosis. They may serve as prognostic markers in children with congenital hydronephrosis.