Expression of class III β-tubulin (βIII-tubulin) correlates with tumor progression and resistance to taxane-based therapies for several human malignancies but its use as a biomarker of tumor behaviour in prostate cancer (PCa) remains largely unexplored. Here, we describe βIII-tubulin immunohistochemical staining patterns of prostate tumors obtained from a broad spectrum of PCa patients, some of whom subsequently received docetaxel therapy for castration-resistant prostate cancer (CRPC). Elevated βIII-tubulin expression was significantly associated with tumor aggressiveness in PCa patients with presumed localized disease as it was found to be an independent marker of biochemical recurrence after treatment. Additionally, βIII-tubulin expression in tumor cells was an independent predictor of lower overall survival for patients receiving docetaxel-based chemotherapy for CRPC. Manipulation of βIII-tubulin expression in human prostate cancer cell lines using a human βIII-tubulin expression vector or βIII-tubulin siRNA altered cell survival in response to docetaxel treatment in a manner that supports a role for βIII-tubulin expression as a mediator of PCa cell resistance to docetaxel therapy. Our findings suggest a role for βIII-tubulin as candidate theranostic biomarker to predict the response to docetaxel-based chemotherapy as well as to target for treatment of docetaxel-resistant CRPC.

We aimed to identify interesting deleted chromosomal regions for bladder cancer diagnosis and carcinogenesis, and to evaluate the association between loss of heterozygosity (LOH) and clinico-pathological parameters. Microsatellite analysis was performed on urine sediment and tumor tissue from 43 consecutive patients with superficial transitional cell carcinoma (TCC) and from 42 consecutive controls. Informative cases were scored as LOH or allelic loss (AL) according to the decrease of the allelic-imbalance ratio. The prevalence of LOH and AL was 39.5% and 86%, respectively. Chromosome 9 was the most frequently altered, especially at 9p (35%). The total number of microsatellite alterations per analysis was correlated with age, grade, stade and EAU classification. The locus 17p13.1 was strongly associated with high-stage (p=0.01) and high-grade tumors (p=0.02). Specificity and sensitivity of LOH was 100% and 39.3% for diagnosis of malignant urinary disease. Specificity and sensitivity of AL was 73.8% and 88%, respectively. Allelic losses are a frequent and early event in bladder cancer, especially at 9p. Thanks to its high specificity, LOH may serve as a complementary tool for non invasive diagnosis of bladder cancer. Further study is warranted to evaluate the prognostic value of LOH on recurrence, progression and muscle invasion.

Developing molecular markers that define high-risk lesions is clinically critical for improving the prognosis determination of the tumors and their treatment. We decided to focus on the two pathways involving FGFR3 and allelic losses at 9p22 to identify a potential combined role in predicting tumor recurrence, progression and/or muscle. Microsatellite and mutational FGFR3 status analyses was performed in tumor tissue of 58 patients in a prospective unicentre study. The results of microsatellite and FGFR3 analyses were dichotomized as follows: loss of heterozygos-ity (LOH) versus retention of heterozygosity (ROH) on the one hand; mutant FGFR3 (mtFGFR3) versus wild-type FGFR3 (wtFGFR3) on the other hand. The combined 9p22/FGFR3 status was strongly correlated with stage (p=0.001) and grade (p<0.001) whereas the single FGFR3 mutational status was not able to predict recurrence, progression or muscle invasion. The survival curves corresponding to each combined status (mtFGFR3/ROH, wtFGFR3/ROH, mtFGFR3/LOH, wtFGFR3/LOH) were significantly different for recurrence (p=0.008), progression (p=0.046) and progression to muscle invasive disease (p=0.004). In case of 9p22 LOH, the FGFR3 mutational status was strongly associated with different clinical outcomes. In a multivariate model, the combined wtFGFR3/9p22 LOH status remained significant in predicting oncologic outcomes. FGFR3 mutations strongly characterize tumors with low malignant potential and favourable clinical outcome in case of allelic losses at 9p22, whereas its prognostic value becomes null or slightly inverts in case of allelic stability. Thus, our findings may also lead to further experiments in order to study interactions between FGFR3 and genes located at 9p22, as CDKN2A.

Therapeutic strategy remains unclear with no clear consensus for men with high-risk prostate cancer after radical prostatectomy. We aimed to evaluate into a prospective randomized trial the effectiveness and the feasibility of adjuvant weekly paclitaxel combined with androgen deprivation therapy (ADT) in these patients. 47 patients with high risk prostate cancer were randomized 6 weeks after radical prostatectomy: ADT alone versus combination of ADT and weekly paclitaxel. Toxicity, quality-of-life and functional results were compared between the two arms. All 23 patients completed 8 cycles of paclitaxel. Toxicity was predominantly of grade 1–2 severity. There were no differences in EORTC QLQ-C30 scores between the two groups and between baseline and last assessment at 24 months after surgery. Urinary continence was complete at one year after surgery for all patients and no significant differences was noted at each assessment between the two groups. The interim analysis of this trial confirms the feasibility of weekly paclitaxel in combination with androgen deprivation therapy in men at high risk prostate cancer with curative intent. This adjuvant combined therapy does no alter quality-of-life and continence recovery after surgery plus ADT. A larger cohort is awaited to determine the oncological outcomes of this strategy.

PURPOSE

To evaluate the incidence of high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP) in initial 21-core extended biopsy scheme and to determine the prostate cancer detection rate in the repeated biopsy.

METHODS

Between 2002 and 2008, 2,006 patients underwent a first 21-core extended biopsy scheme. Incidences of cancer, ASAP and HGPIN were studied. Cancer detection rate in the repeated 21-core extended biopsy for ASAP and HGPIN was reported and compared with those obtained on repeated biopsy for clinico-biological indications.

RESULTS

Incidences of HGPIN and ASAP were 1.7% and 1.1%, respectively. The 6-core and 12-core biopsy schemes detecting HGPIN would have missed the diagnosis of cancer in 10% and 3.6% of cases, compared to a 21-core biopsy protocol, respectively. The cancer detection rate on repeated biopsy for HGPIN was 19% and not significantly different compared with the detection rate on repeated biopsy for clinico-biological indications (16.8%, p=0.77). Seven prostate cancers were found among the 17 re-biopsies for ASAP revealing a detection rate of 41.2% (p=0.01). All detected cancers were organ-confined. No clinico-pathological data was independent predictor of cancer on repeated biopsy.

CONCLUSION

Our report demonstrates the different risk profiles for HGPIN and ASAP in a 21-core extended biopsy scheme. Presence of HGPIN does not imply a higher risk for cancer detection at immediate re-biopsy compared to other patients for who repeated biopsies were indicated for increasing or persistently increased PSA levels. Repea biopsy is warranted when ASAP is diagnosed because of a high risk of prostate cancer.

Introduction

The aim of this study is to review 10 years experience of retroperitoneoscopy procedures.

Methods

600 patients treated between 1995 and 2007 netroperitoneoscopy (nephrectomy, partial and total nephrectomy, adrenalectomy, pyeloplasty, renal cyst, calyceal diverticulectomy) were reviewed for per, peri and post operative complications including patients in the learning curve.

Results

The mean blood loss was 159mL. Conversion to open surgery was required in 28 patients (4.6%) primarily due to technical problems during dissection (elective). There were 32 (5.3%) surgical complications, including bleeding or hematomas in 12 cases and 2 of them required reintervention, urinomas in 8 which were treated by installation of a ureteral drainage (JJ stent). Wound or deep abscesses happened in 4, urinary fistula in 1 and pancreatic fistula in another. Evisceration (hernias) was seen in 3 patients. Intestinal injury occurred in 2. The complication rate depended on the difficulty of the procedure and learning curve of the surgeon. Twenty eight patients (4.6%) presented medical post-operative complications (hyperthermias, deep venous thrombosis, pyelonephritis, pulmonary superinfections, pulmonary atelectasia and transient vascular ischemic accident). Mean postoperative hospital stay was 6.2 days (ranged from 2 to 20).

Conclusion

Retroperitoneoscopy can be the technique of choice for accessing and carrying out all the surgery of the upper urinary tract respecting the principles of oncological surgery. After experience with 600 cases during the last 10 years the technique has become safe, simplified, reproducible and effective although not easy. Most complications are minor and easily managed.