The survival impact of neoadjuvant hormonal therapy before radical prostatectomy for treatment of high-risk prostate cancer.

BACKGROUND: Several randomized controlled trials assessed the outcomes of patients treated with neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP). The majority of them included mainly low and intermediate risk prostate cancer (PCa) without specifically assessing PCa-related death (PCRD). Thus, there is a lack of knowledge regarding a possible effect of NHT on PCRD in the high-risk PCa population. We aimed to analyze the effect of NHT on PCRD in a multicenter high-risk PCa population treated with RP, using a propensity-score adjustment. METHODS: This is a retrospective multi-institutional study including patients with high-risk PCa defined as: clinical stage T3-4, PSA >20 ng ml-1 or biopsy Gleason score 8-10. We compared PCRD between RP and NHT+RP using competing risks analysis. Correction for group differences was performed by propensity-score adjustment. RESULTS: After application of the inclusion/exclusion criteria, 1573 patients remained for analysis; 1170 patients received RP and 403 NHT+RP. Median follow-up was 56 months (interquartile range 29-88). Eighty-six patients died of PCa and 106 of other causes. NHT decreased the risk of PCRD (hazard ratio (HR) 0.5; 95% confidence interval (CI) 0.32-0.80; P=0.0014). An interaction effect between NHT and radiotherapy (RT) was observed (HR 0.3; 95% CI 0.21-0.43; P<0.0008). More specifically, of patients who received adjuvant RT, those who underwent NHT+RP had decreased PCRD rates (2.3% at 5 year) compared to RP (7.5% at 5 year). The retrospective design and lack of specific information about NHT are possible limitations. CONCLUSIONS: In this propensity-score adjusted analysis from a large high-risk PCa population, NHT before surgery significantly decreased PCRD. This effect appeared to be mainly driven by the early addition of RT post-surgery. The specific sequence of NHT+RP and adjuvant RT merits further study in the high-risk PCa population.

Tumour thrombus consistency has no impact on survival in patients with renal cell carcinoma.

The prognosis of renal cell carcinoma (RCC) with venous tumour thrombus (VTT) is variable and not always possible to predict. The prognostic impact and independence of tumour thrombus-related factors including the recently introduced tumour thrombus consistency (TTC) on overall survival remain controversial. The aim of this study was to investigate the prognostic role of TTC in patients' survival. We determined the tumour thrombus consistency (solid vs. friable) in a cohort of 84 patients with RCC and VTT who underwent nephrectomy with thrombectomy, and performed a retrospective evaluation of the patients' data from the prospectively maintained database. A total of 45% of patients had solid thrombus (sTT) and 55% had friable thrombus (fTT). The venous tumour thrombus consistency was not predictive of overall survival. Further studies, preferably prospective and with a larger number of patients, are needed to validate the obtained results, as well as to evaluate the usefulness of tumour thrombus consistency in clinical practice for stratifying the risk of recurrence and planning further follow-up.

Older patients with low Charlson score and high-risk prostate cancer benefit from radical prostatectomy.

INTRODUCTION: The aim of the study was to identify the appropriate level of Charlson comorbidity index (CCI) in older patients (>70 years) with high-risk prostate cancer (PCa) to achieve survival benefit following radical prostatectomy (RP). METHODS: We retrospectively analyzed 1008 older patients (>70 years) who underwent RP with pelvic lymph node dissection for high-risk prostate cancer (preoperative prostate-specific antigen >20 ng/mL or clinical stage ≥T2c or Gleason ≥8) from 14 tertiary institutions between 1988 and 2014. The study population was further grouped into CCI < 2 and ≥2 for analysis. Survival rate for each group was estimated with Kaplan-Meier method and competitive risk Fine-Gray regression to estimate the best explanatory multivariable model. Area under the curve (AUC) and Akaike information criterion were used to identify ideal 'Cut off' for CCI. RESULTS: The clinical and cancer characteristics were similar between the two groups. Comparison of the survival analysis using the Kaplan-Meier curve between two groups for non-cancer death and survival estimations for 5 and 10 years shows significant worst outcomes for patients with CCI ≥ 2. In multivariate model to decide the appropriate CCI cut-off point, we found CCI 2 has better AUC and p value in log rank test. CONCLUSION: Older patients with fewer comorbidities harboring high-risk PCa appears to benefit from RP. Sicker patients are more likely to die due to non-prostate cancer-related causes and are less likely to benefit from RP.

Selected immunohistochemical features of conventional renal cell carcinomas coexpressing P53 and MDM2.

Renal clear cell carcinoma (CCRCC) is an aggressive tumor for which new prognostic factors are needed. It has been suggested that CCRCCs co-expressing P53 and MDM2 could represent a special subgroup; therefore the aim of this study was to explore their immunohistochemical features. The material studied consisted of 470 cases of CCRCC. Immunohistochemistry for MDM2, P53, Ki-67, VEGF-A, VEGF-C, VEGF-D, GLUT1, CA9, and CK 7 was performed on tissue microarrays and assessed semi-quantitatively. On average, 6.6% or 5.3% of cases were P53+/MDM2+, depending on the P53 antibody used. The mean percentage of Ki-67 positive cells was 0.6% and p53-positive MDM2-positive cases showed significantly higher expression of Ki-67. The other immunohistochemical parameters studied did not differ between p53-positive MDM2-positive cases and the rest of the subtypes studied. Expression of almost all immunohistochemical markers differed with respect to pT stage; only for CA9 was the difference not significant. Furthermore, almost all immunohistochemical markers studied differed with respect to differences in grade; only for GLUT1 was the difference not significant. Our results suggest that with the exception of Ki-67, there are no significant associations between analyzed markers and the double P53+/MDM2+ phenotype.

Morphological and urodynamic evaluation of urinary bladder wall regeneration: muscles guarantee contraction but not proper function--a rat model research study.

BACKGROUND: Numerous studies are ungoing to develop a substitute for the native urinary bladder wall. The principals of tissue engineering approaches to urinary bladder wall augmentation require a favorable environment for smooth muscle regeneration, which is crucial for bladder function. This study was performed to evaluate bone marrow mesenchymal stem cells (BMSC) seeded on to amniotic membranes fixed to Tachosil sponges as grafts for urinary bladder muscle layer augmentation in a syngenic rat model. MATERIALS AND METHODS: Amniotic membranes seeded with BMSC and covered by Tachosil sponges were implanted as multilayer grafts into nine rats to regenerate the urinary bladder wall. The control group consisted of 12 healthy rats. Urodynamic examinations included contraction, elasticity, compliance, and urinary bladder motor activity. Hematocylin and eosin and Masson's trichrome stains were used to evaluate muscle regeneration; histological data were digitally analyzed with the ImageJ tool. RESULTS: The area of muscle bundles ranged from 5% to 25% or 32% to 41% in control versus reconstructed bladders, respectively. Among nine animals with reconstructed urinary bladders, urodynamic evaluation revealed bladder motor hyperactivity with regular (n = 4) or irregular (n = 1) storage and voiding phases, as well as proper bladder motor activity with a large bladder capacity (n = 1). No bladder contractility was recorded in one case and large stones developed in two animals, which made functional studies impossible. CONCLUSIONS: Regenerated smooth muscle cells created an autonomic cell population that was poorly assimilated to the rest of the urinary bladder wall. The histological presence of a regenerated muscle layer did not guarantee proper urinary bladder function.

[Radical cystectomy - pro laparoscopic]. / Radikale Zystektomie - pro laparoskopisch.

Although the technical feasibility of laparoscopic radical cystectomy (LRC) has been proven and the procedure has been accepted in the EAU guidelines 2011 as a valid alternative, its actual position has to be determined. On the one hand the advantages of LRC (less blood loss, lower transfusion rates, shorter analgesia time) have been proven in retrospective studies; however, the technical difficulties of purely laparoscopic urinary diversion result in very long operating times and in cases of a laparoscopic-assisted creation of a neobladder, the question of the advantage of this approach remains doubtful. Despite case reports of port metastases and peritoneal carcinosis following laparoscopic and robot-assisted radical cystectomy, there is no difference in terms of oncological long-term data (up to 10 years) between laparoscopy and open surgery performed at centres of excellence. Evidently, the curative options for the patients do not depend on the type of surgery (open versus minimally invasive) but on the efficacy of adjuvant treatment strategies (polychemotherapy). Currently it is believed that LRC should be considered for patients with low risk of progression (pT1-2). The final position of laparoscopic radical cystectomy can only be evaluated in a multicentric randomized controlled trial.

Prostate cancer which affects an elderly man is a feature of senescence (cellular) - a biology phenomenon.

UNLABELLED: Some prostate cancers are clinically significant (i.e. life-threatening) but others are not. Small proportion of elderly men dies of prostate cancer while most of them harbor tumor lesions in their prostates. The aim of this paper was to present late-life form of the prostate cancer, which differs from its aggressive counterpart that affects men between 55-65 years old and younger. The differences can be found in carcinogenesis risk factors, cancer biology and finally patients' survival. The most important is that these two clinical (age-related) forms of the prostate cancer are still undistinguishable in clinico-pathology reports and patients bearing different diseases are offered the same treatment. Potential mechanisms leading to development of the late-life clinically indolent prostate cancer are discussed. It seems that the key abnormalities are proteins involved in control of regenerative potential and cell senescence. CONCLUSIONS: We postulate that late-life low-grade (clinically indolent) prostate cancer subcategory should be established. This type of «cancer¼ should rather be viewed as a senescence-related feature and probably not treated at all.