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Purpose: Predictive factors of T1 nonmuscle invasive bladder cancer evolution that could guide treatment decision making are lacking. We assessed the prognostic value of muscularis mucosa invasion in nonmuscle invasive bladder cancer., Materials and Methods: In a national multicenter study patients with primary T1 nonmuscle invasive bladder cancer were recruited from 6 French hospitals. All patients had undergone transurethral resection of bladder tumor. All T1 tumors were substaged according to muscularis mucosa invasion as T1a-no invasion beyond the muscularis mucosa or T1b-invasion beyond the muscularis mucosa with muscle preservation. Subsequent central pathology review was then done by a single referent uropathologist. Muscularis mucosa invasion was tested as a prognostic factor for survival on univariate and multivariate analysis., Results: A total of 587 patients were enrolled in the study, including 388 (66%) with T1a and 199 (34%) with T1b tumors. Median followup after transurethral resection of bladder tumor was 35 months (IQR 14-54). There was no significant difference between groups T1a and T1b except high tumor grade in T1b cases (p <0.0001). After central review, initial pathological substaging was confirmed in 84% of cases. On multivariate analysis muscularis mucosa invasion (T1b substage) was significantly associated with recurrence-free (p = 0.03), progression-free (p = 0.0002) and cancer specific (p = 0.02) survival. The main study limitation was absent systematic subsequent transurethral resection of bladder tumor., Conclusions: Muscularis mucosa invasion appears to be highly predictive of T1 nonmuscle invasive bladder cancer behavior. Consequently, systematic T1a vs T1b discrimination should be highly advocated by urologists and pathologists. We believe that it could aid in crucial decision making when choosing between conservative management and radical cystectomy remains a moot point., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Despite increasing evidence that estrogen signaling has a key role in prostate cancer development and progression, few studies have focused on the estrogen pathway in the transition from hormone sensitive to hormone refractory tumors. We investigated the expression of proteins related to androgen and estrogen metabolism in paired prostate cancer samples collected before androgen deprivation therapy and after hormonal relapse., Materials and Methods: The study included 55 patients treated for prostate cancer only with androgen deprivation therapy and in whom tissue was available before treatment induction and after recurrence. Immunohistochemistry was performed using tissue microarray with antibodies directed against androgen receptor, phosphorylated androgen receptor, estrogen receptor α, estrogen receptor β, 5α-reductase 1 and 2, aromatase, BCAR1 and the proliferation marker Ki67., Results: Compared to hormone sensitive samples, tissues collected after hormonal relapse were characterized by increased expression of Ki67, androgen receptor, phosphorylated androgen receptor (p <0.001) and BCAR (p = 0.03), and by lower staining for 5α-reductase 2 (p = 0.002), estrogen receptor β (p = 0.016) and aromatase (p <0.001). Shorter time to hormonal relapse was associated with high expression of aromatase and BCAR1 on diagnostic biopsy, together with low staining for estrogen receptor α in stromal cells. Overall survival was significantly shorter when tissues collected after relapse showed a high proliferation index and low estrogen receptor α expression., Conclusions: Results revealed dysregulation of proteins involved in androgen pathways, and in estrogen synthesis and signaling during the development of hormone refractory prostate cancer., (Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Since October 2001 we have performed intraoperative frozen section (IFS) on the posterolateral areas of the radical prostatectomy specimen with bilateral nerve sparing. In cases of positive surgical margin (SMs) the corresponding neurovascular bundle (NVB) was resected. We evaluated the impact of several biological and pathological parameters on the incidence of local residual tumor in the NVB., Materials and Methods: A total of 487 laparoscopic radical prostatectomies with bilateral nerve sparing and IFS were performed between October 2001 and December 2003. When IFS was positive, the whole NVB was removed and analyzed after fixation in serial sections. The size of the positive SM was measured in its largest dimension. The association of NVB residual tumor with positive SM size, preoperative prostate specific antigen, pathological stage and Gleason score was analyzed using the t and chi-square tests, and logistic regression., Results: Of the 487 patients 84 had a positive SM on IFS. In 25 of the 84 additionally resected NVBs we found residual tumor. On univariate and multivariate analysis the only predictor of residual tumor was positive SM size (p<0.001). In all cases of a positive SM of 0.1 cm or less we found no residual tumor cells in the NVB., Conclusions: In case of a positive SM in the posterolateral area of the prostatectomy specimen margin size is predictive of the incidence of residual tumor in the corresponding NVB. This finding could help management and the decision about local adjuvant treatment.

Purpose: Benign prostatic hyperplasia (BPH) is characterized by a hyperplastic growth of epithelial and stromal cells in the prostate. Despite the high prevalence of the disease little is known regarding the molecular etiology of BPH. Therefore, a comparison of gene expression patterns between normal prostate, BPH and prostate cancer could provide insights into the pathogenic mechanisms of the disease and identify candidate genes that could be targeted for therapeutic use., Materials and Methods: Prostate tissue specimen were obtained from 30 patients undergoing adenomectomy for BPH. Adenoma weight was less than 60 gm in 15 patients and more than 60 gm in the remainder. Normal prostate tissue was obtained from 15 patients undergoing radical prostatectomy for cancer from areas selected for absent tumor and BPH. Two pools of organ confined prostate cancer were also analyzed. We quantified in the 5 pools of tissues the expression of 327 genes using real-time quantitative reverse transcriptase-polymerase chain reaction., Results: A total of 23 genes showed increased expression in BPH with a fold change of at least 2.5 between normal prostate and the 2 BPH groups, of which most were normal or down-regulated in prostate cancer. Seven genes showed decreased expression in BPH with a fold change of at least 3.5 between normal prostate and BPH. Most of them were also normal or down-regulated in prostate cancer., Conclusions: We identified a set of genes up-regulated in BPH compared to normal prostate tissue and often prostate cancer, including genes previously implicated in BPH and others not previously linked to this disease to our knowledge. Further investigations are now warranted to determine the clinical relevance and therapeutic potential of these genes.

Purpose: Nerve sparing radical prostatectomy may allow preservation of potency but it can increase positive surgical margins. We used intraoperative frozen section (IFS) analysis to monitor the nerve sparing procedure in laparoscopic prostatectomy., Materials and Methods: A total of 100 patients with localized prostatic carcinoma underwent bilateral intrafascial nerve sparing laparoscopic prostatectomy with IFS. A wedge of tissue was cut from base to apex in the region of the neurovascular bundles (NVBs) and analyzed on frozen section. If carcinoma was detected at the inked margin, the corresponding NVB was resected. Definitive margin status was evaluated after permanent section analysis of IFS prostatectomy specimens and eventually NVB specimens., Results: IFS analysis was positive in 24 patients, as confirmed in all by permanent section of the wedges. Three of these patients had positive margins in the prostate specimen at another site. Of the 76 tumors with negative IFSs 1 had positive margins on permanent sections of the wedges and 8 had positive margins on the prostate specimen at another site. IFS led to a decrease in the overall positive margin status from 33% to 12% and from 26.1% to 7.9% in pT2 tumors. Tumor was found on NVB resection in 8 cases (33%)., Conclusions: These results suggest that IFS analysis is a reliable method by which to monitor nerve sparing during laparoscopic prostatectomy. IFS could allow the surgeon to offer a nerve sparing procedure more frequently without compromising cancer control.

Purpose: Loss of heterozygosity (LOH) is the most consistent genetic alteration in prostate cancer (CaP), frequently associated with advanced cancer and metastasis. We performed LOH analysis on 6 chromosomal regions of interest in localized CaP to obtain an overview of allelic losses in organ confined tumors and test the association with the usual prognostic factors., Materials and Methods: Tumoral and normal DNA were extracted from 48 radical prostatectomy specimens (all organ confined) with a Gleason score of 5 to 7. Biological and pathological data, such as prostate specific antigen (PSA), Gleason score and perineural invasion (PNI), were correlated with allelic losses at 7q31, 8p22, 12p13, 13q14, 16q23.2 and 18q21. Analysis was done by genotyping using highly informative microsatellites markers., Results: The rate of LOH was 25% for chromosomes 13 and 18, and between 40% and 47% for chromosomes 7, 8, 12 and 16. The mean frequency of overall LOH events was less than 34%. Except for the 12p13 and 16q23.2 loci no significant correlation was found between LOH and PSA or Gleason score. PNI was significantly associated with LOH on 8p22 (p = 0.003) and with a high frequency of LOH events (greater than 34%) (p = 0.02)., Conclusions: The frequency of allelic losses in localized and differentiated CaP is associated with PNI but not with the usual prognostic markers, such as PSA and Gleason score. The relationship between LOH on 8p22 and PNI suggests the presence on this region of a gene involved in epithelium/nerve interaction.

Purpose: To minimize the risk of incontinence and impotence without compromising oncological outcome, we performed prostate sparing surgery during radical cystectomy for bladder cancer., Materials and Methods: Since 1992, 100 patients with a mean age of 64 years (range 48 to 82) underwent cystectomy for bladder transitional cell carcinoma with prostate sparing based on normal digital rectal examination of the prostate, normal prostate specific antigen (PSA), percent free PSA greater than 15 and normal transrectal ultrasound of the prostate. Prostate biopsies to exclude prostate cancer were performed on patients with an abnormal digital rectal examination, high PSA, percent free PSA less than 15 or hypoechoic lesions on ultrasound. Surgery consisted of transurethral resection of the prostate with analysis of frozen section of the prostatic urethra and transitional prostate and cystectomy with reconstruction by a Z ileal bladder anastomosed to the prostatic capsule after confirmation of the absence of prostate or bladder cancer on frozen sections of the surgical capsule specimens. Patients were followed closely with imaging and laboratory studies every 6 months and annually for 3 years thereafter., Results: Perioperative death occurred in 1 patient due to septicemia, 20 patients (20%) died of cancer and 6 (6%) died of nonrelated cancer causes. Mean followup 38 months (range 2 to 111). Postoperative pathological stage was PT0 in 2 cases, PtaT1 in 22, PT2 in 48, PT 3 in 28 and N+ in 13. The 5-year actuarial global survival according to pathological stage was pTaT1N0 in 96% of cases, pT2N0 in 83%, pT3N0 in 71% and N+ in 54% (p = 0.0001). The 5-year actuarial cancer specific survival was PT0, Ta T1 in 90% of cases, PT2 in 73%, PT3 in 63% and N- in 8%. The cancer specific survival according to pathological grade was 100% for well differentiated tumors (grade I), 76% for moderately differentiated tumors (grade II) and 47% for poorly differentiated tumors (grade III) (p = 0.003). Local recurrence was pTaT1N0 in 1 of 22 cases (4.5%), pT2N0 in 2 of 40 (5%), pT3N0 in 2 of 23 (8.5%) and N+ in 0 of 13 (0%). Prostate cancer was diagnosed in 3 patients (2 errors in the diagnosis and 1 cancer de novo within 5 years of followup). At 1-year followup 86 of 88 patients (97%) are fully continent (no pad) during the day, and 84 (95%) void 1 to 2 times a night to stay dry. Of 61 patients with previously adequate sexual function 50 (82%) maintained potency with retrograde ejaculation secondary to transurethral resection, 6 (10%) have partial potency and 5 (8.1%) are impotent., Conclusions: Cystectomy with prostate sparing for bladder cancer is feasible and offers promising functional results with no additional oncological risk. Careful selection of patients is mandatory.