Search

Background: Controversy exists regarding the risk of cardiovascular disease (CVD) associated with androgen deprivation therapy (ADT) in patients with prostate cancer. We sought to evaluate the association between gonadotropin-releasing hormone (GnRH) agonists versus GnRH antagonist and the risk of CVD in patients with prostate cancer with or without prior CVD. Patients and Methods: Using administrative databases from Quebec, Canada, we identified first-time GnRH agonists and antagonist (degarelix) users between January 2012 and June 2016. Follow-up ended at the earliest of the following: first CVD event (myocardial infarction [MI], stroke, ischemic heart disease [IHD], arrhythmia, and heart failure [HF]); switch of GnRH group; death; or December 31, 2016. Inverse probability of treatment weighting (IPTW) based on the propensity score was used to control for potential confounding. IPTW-Cox proportional hazards model accounting for competing risks was used to evaluate the association of interest. Results: Among 10,785 patients identified, 10,201 and 584 were on GnRH agonists and antagonist, respectively. Median age was 75 years (interquartile range, 69–81 years) for both groups. A total of 4,152 (40.7%) men in the GnRH agonists group and 281 (48.1%) men in the GnRH antagonist group had CVD in the 3-year period prior to ADT initiation. Risk of HF was decreased in the antagonist group compared with the GnRH agonist group among patients with prior CVD (hazard ratio [HR], 0.46; 95% CI, 0.26–0.79). Risk of IHD was decreased in the antagonist group in patients without prior CVD (HR, 0.26; 95% CI, 0.11–0.65). Use of antagonist was associated with an increased risk of arrhythmia among patients with no prior CVD (HR, 2.34; 95% CI, 1.63–3.36). Conclusions: Compared with GnRH agonists, the GnRH antagonist was found to be associated with a decreased risk of HF, specifically among patients with prior CVD. Among those with no prior CVD, the GnRH antagonist was associated with a decreased risk of IHD but an increased risk of arrhythmia.

238 Background: Androgen deprivation therapy (ADT) is a staple of advanced prostate cancer (PCa) treatment, however several side-effects are associated with its long-term use. Notably, loss of bone mineral density (BMD) is accelerated which increases fracture risk. Although guidelines recommend BMD testing when initiating ADT to properly assess baseline fracture risk, there is limited data to support this recommendation in the PCa patient population. The objective was to examine the association between baseline BMD testing (bBMDT) and the risk of fractures in men initiating ADT for PCa. Methods: A retrospective observational cohort study using data from Quebec public healthcare insurance administrative databases was conducted. The cohort included PCa patients who initiated ADT from 2004-2015 and who received at least one year of ADT treatment. Baseline BMD testing was defined as a BMD test performed from 6 months prior to ADT initiation and up to 3 months after. Patients were categorized as either having received bBMDT or not received bBMDT when initiating ADT. The primary study outcomes were incidence of any fracture and incidence of fractures resulting in hospitalization. Inverse probability of treatment weighting was used to adjust for measured baseline characteristics which included patient demographic variables, comorbidities, risk factors for fractures, and use of other medications affecting bone density. Results: We identified 13,532 patients who initiated ADT, of which 2,070 (15.3%) underwent bBMDT. The unadjusted 5-year incidence of any fracture was 15.1% for patients not receiving bBMDT and 14.0% for patients receiving bBMDT. In adjusted analyses, bBMDT (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.76-1.12) was not associated with the risk of any fracture. For fractures requiring hospitalization, bBMDT was associated with a lower risk (HR 0.71, 95%CI 0.52-0.98). Furthermore, bBMDT was associated with increased odds of bisphosphonate use within 1 year of ADT initiation among patients who were bisphosphonate-naïve at baseline (odds ratio [OR] 2.03, 95%CI 1.74-2.36). Conclusions: In our study population, bBMDT was associated with a lower risk of fractures resulting in hospitalization. Given the low uptake of bBMDT, additional efforts emphasizing the importance of BMD testing in guidelines may be needed.

Prostate cancer (PCa) metastases are highly enriched with genomic alterations including a gain at the 16p13.3 locus, recently shown to be associated with disease progression and poor clinical outcome. ECI1, residing at the 16p13.3 gain region, encodes Δ3, Δ2-Enoyl-CoA Delta Isomerase 1 (ECI1), a key mitochondrial fatty acid β-oxidation enzyme. Although deregulated mitochondrial fatty acid β-oxidation is known to drive PCa pathogenesis, the role of ECI1 in PCa is still unknown. We investigated the impacts of ECI1 on PCa phenotype in vitro and in vivo by modulating its expression in cell lines and assessed the clinical implications of its expression in human prostate tissue samples. In vitro, ECI1 overexpression increased PCa cell growth while ECI1 deficiency reduced its growth. ECI1 also enhanced colony formation, cell motility, and maximal mitochondrial respiratory capacity. In vivo, PCa cells stably overexpressing ECI1 injected orthotopically in nude mice formed larger prostate tumors with higher number of metastases. Immunohistochemistry analysis of the human tissue microarray representing 332 radical prostatectomy cases revealed a stronger ECI1 staining in prostate tumors compared to corresponding benign tissues. ECI1 expression varied amongst tumors and was higher in cases with 16p13.3 gain, high Gleason grade, and advanced tumor stage. ECI1 overexpression was a strong independent predictor of biochemical recurrence after adjusting for known clinicopathologic parameters (hazard ratio: 3.65, P 0.001) or the established CAPRA-S score (hazard ratio: 3.95, P 0.001). ECI1 overexpression was also associated with significant increased risk of distant metastasis and reduced overall survival. Overall, this study demonstrates the functional capacity of ECI1 in PCa progression and highlights the clinical implication of ECI1 as a potential target for the management of PCa.

To the authors' knowledge, the literature to date lacks studies examining lifetime costs and quality-adjusted life-years (QALYs) of prostate cancer (PCa) management strategies that integrate localized and advanced disease. The objective of the current study was to assess lifetime costs and QALYs associated with contemporary PCa management strategies across risk groups by integrating localized and advanced disease.The authors' validated Markov chain Monte Carlo model was used to predict lifetime direct costs and QALYs. The health states modeled were active surveillance, initial treatments (radical prostatectomy or radiotherapy), PCa recurrence, PCa recurrence free, metastatic castration-resistant prostate cancer, and death (cause specific/other causes). Data regarding treatment distribution, state transition probabilities, adverse effects of management options, costs, utilities, and disutilities were derived from the published literature.The total cost per patient for the overall cohort increased from $18,503 at 5 years to $28,032 and $39,143, respectively, at 10 years and 15 years. Furthermore, the results indicated the influence of risk group on total cost, with the high-risk group accruing the maximum per patient cost followed by the intermediate-risk and low-risk groups. Active surveillance was found to confer the most QALYs (12.5 years) and was the least costly strategy ($18,452) for individuals at low risk. For all risk groups, radical prostatectomy was less costly and conferred modestly more QALYs compared with intensity-modulated radiotherapy modalities.Public health care systems in Canada and elsewhere are operating under budget constraints to allocate finite resources. The findings of the current study might inform discussions concerning budget planning to provide health care services.

Intratumoral androgen formation may be a factor in the development of prostate cancer (PCa), particularly castration-resistant prostate cancer (CRPC). To evaluate the ability of the human prostate to synthesize de novo steroids, we examined the expression of key enzymes and proteins involved in steroid biosynthesis and metabolism.Using TissueScan™ Cancer qPCR Arrays and quantitative RT-PCR, we performed comparative gene expression analyses between various prostate cell lines and biopsies, including normal, hyperplastic, cancerous, and androgen-deprived prostate cells lines, as well as normal, benign prostate hyperplasia (BPH), PCa, and CRPC human specimens. These studies were complemented with steroid biosynthesis studies in normal and BPH cells.Normal human prostate WPMY-1 and WPE1-NA22, benign prostate hyperplasia BPH-1, and cancer PC-3, LNCaP, and VCaP cell lines, as well as normal, BPH, PCa, and CRPC specimens, were used. Although all cell lines express mRNA encoding for hydroxymethylglutaryl-CoA reductase (HMGCR), the mitochondrial translocator protein TSPO and cholesterol side chain cleavage enzyme CYP11A1 were only observed in WPMY-1, BPH-1, and LNCaP cells. HSD3B1, HSD3B2, and CYP17A1 are involved in androgen formation and were not found in most cell lines. WPE1-NA22 and BPH-1 cells were unable to synthesize de novo steroids from mevalonate. Moreover, androgen-deprived cells did not have alterations in the expression of enzymes that could lead to de novo steroid formation. All prostate specimens expressed TSPO and CYP11A1. HSD3B1/2, CYP17A1, HSD17B5, and CYP19A1 mRNA expression was distinct to the profile observed in cells lines. The majority of BPH (90.9%) and PCa (83.1%) specimens contained CYP17A1, compared to control (normal) specimens (46.7%). BPH (82%), PCa (59%), normal (40%), and CRPC (34%) specimens expressed the four key enzymes that metabolize cholesterol to androgens.These studies question the use of prostate cell lines to study steroid biosynthesis and demonstrate that human prostate samples contain transcripts encoding for key steroidogenic enzymes and proteins indicating that they have the potential to synthesize de novo steroids. We propose CYP17A1 as a candidate enzyme that can be used for patient stratification and treatment in BPH and PCa.

The aim of this case series is to present two cases of renal granulomas discovered incidentally post-intravesical Bacillus Calmette-Guerin (BCG) installations and were managed conservatively.The first case is a 68-year-old man with bladder and right ureteral orifice carcinoma in situ. After transurethral resection of the right ureteral orifice and bladder tumours, he received 6 + 3 weekly intravesical installations of BCG and then 6 + 3 weekly intravesical installations of BCG with interferon alpha (IFN) in the presence of an indwelling ureteral stent since he had refused cystoprostatectomy. At the 18-month follow-up, his computed tomography scan showed two right renal masses. Biopsy demonstrated non-necrotizing granulomatosis. Serial follow-up with imaging studies showed complete resolution of these masses without anti-tuberculous medications. The second case is a 74-year old man with left renal high-grade papillary urothelial carcinoma. After ureteral meatotomy and insertion of indwelling ureteral stents, he received 6 weekly intravesical installations of BCG followed by 3 weekly installations of BCG and IFN prior to the definitive management with laparoscopic left nephroureterectomy. Final pathology showed pT1 urothelial carcinoma and an incidental finding of BCG-related renal granulamotosis. The patient has been asymptomatic and did not require anti-tuberculous medications.While these two cases demonstrate the ability of intravesical BCG to reach the renal pelvis, patients with a history of intravesical BCG with incidental renal masses may benefit from renal biopsy. These renal granulomas may resolve without anti-tuberculous medications.

OBJECTIVE To examine the relationship of serum insulin-like growth factor (IGF)-1 and IGF binding protein-3 (IGFBP-3) with histological cancer characteristics in men undergoing transrectal ultrasonography (TRUS)-guided biopsy. PATIENTS AND METHODS Patients (652), with either an elevated serum prostate-specific antigen level or an abnormal digital rectal examination, were initially evaluated by TRUS and sextant prostatic needle biopsy. Blood was drawn before biopsy, serum extracted and stored frozen until IGF-1 and IGFBP-3 were measured. In all, 241 patients had prostate cancer (37%) and were included in this study. The number of positive biopsies, the volume of tumour in each positive biopsy and the Gleason score were recorded. RESULTS Of the 241 patients, 37 had five or six positive biopsies (from six), 128 had two to four and 76 had one. Serum IGF-1 did not correlate with the number of positive biopsies, with means of 176.7, 178.3 and 164.4 ng/mL, respectively (P = 0.3), while the mean IGFBP-3 was 2695, 2795 and 2572 ng/mL, respectively (P = 0.09). The additive percentiles of tumour volume in positive biopsies were assessed for each patient but serum IGF-1 and IGFBP-3 did not correlate (P = 0.7 and 0.9, respectively). In all, 92 patients had a Gleason score of 7; the mean (sd) IGF-1 levels for the three groups were 181 (39), 174.6 (35) and 176 (26) ng/mL, and the mean IGFBP-3 2798 (240), 2735 (284) and 2647 (221) ng/mL, respectively, none of the differences being statistically significant. CONCLUSIONS Serum IGF-1 and IGFBP-3 do not correlate with quantity of cancer or Gleason score in biopsy samples from patients with prostate cancer.

BACKGROUND Mechanisms triggering prostatic NE differentiation are poorly understood. Since dog and man naturally develop prostatic proliferative diseases with age, our objectives were to confirm the presence of NE cells in the dog prostate and test their hormonal regulation in both species. METHODS Serotonin staining was examined by immunohistochemistry in 37 dog prostates: 17 from intact and 20 from castrated animals. In intact dogs, 9 prostates were normal and 8 hyperplastic. In the castrated group, 6 dogs were left untreated while androgens and estrogens were administered to 7 dogs, each. Human prostates were from 48 prostate cancer patients; half of them were submitted to androgen ablation prior to prostatectomy. The density of serotonin-positive NE cells was expressed relatively to the number of acini. RESULTS Serotonin-positive NE cells were morphologically similar in dog and human prostates and identified in all groups, independent of the hormonal status. NE cell densities were within the same range in normal and hyperplastic dog prostates but significantly higher after castration. Androgens and estrogens after castration restored NE cell density to normal values and induced luminal differentiation and basal metaplasia, respectively. In human, the density of serotonin-positive NE cells was also significantly higher in benign glands after androgen ablation. CONCLUSIONS The dog is a suitable animal model and mimics the human, since androgen ablation favored prostatic NE differentiation in both species. The down-regulation elicited by steroids suggests that the process may be reversible and hormonally-repressed. Prostate 51: 117–125, 2002. © 2002 Wiley-Liss, Inc.

To document radical cystectomy (RC) outcomes in patients over 80 years old across Quebec during the years 2000-2009 and to examine potentially related factors.Within Quebec health insurance medical services database, we identified patients over 80 years who underwent RC. The outcomes analyzed were post-operative complications, mortality rates at 30, 60 and 90 days and overall survival.A total of 275 patients over 80 years old had RC performed in 38 hospitals across Quebec. Among them, 33% had major post-operative complications with 16% having more than one complication. Mortality rates at 30, 60 and 90 days were 5.8%, 9.8% and 13% respectively. 44.3% of RCs were performed in seven academic hospitals with mortality rates of 2.5%, 6.5% and 9% respectively. Community hospitals had mortality of 8.5%, 12.4% and 16.3% respectively (P 0.001). The cohort 5-year overall survival rate was 27%. The presence of post-operative complications and the number of complications negatively affected overall survival (P 0.001) CONCLUSION: Patients over 80 years of age have high post-RC mortality rates, especially at 90 days. In addition, it appears that they have lower post-operative mortality if their RCs were performed in academic centers. Mortality rates and complications can be used when obtaining informed consent.

To evaluate the clinical and pathological factors influencing the risk of disease progression in a cohort of patients with low-intermediate risk prostate cancer under active surveillance (AS).We studied 300 patients diagnosed between 1992 and 2012 with prostate adenocarcinoma with favourable parameters or who refused treatment and were managed with AS. Of those, 155 patients with at least one repeat biopsy and no progression criteria at the time of the diagnosis were included for statistical analyses. Patients were followed every 3-6 months for prostate-specific antigen (PSA) measurement and physical examination. Patients were offered repeat prostatic biopsy every year. Disease progression was defined as the presence of one or more of the following criteria: ≥ 3 positive cores,50% of cancer in at least one core, and a predominant Gleason pattern of 4.For the 155 patients, the mean (sd) age at diagnosis was 67(7) years; the median (interquartile range) follow-up was 5.4(3.6-9.5) years. Of these, 67, 25, six, and two patients had two, three, four, and five repeat biopsies, respectively. At baseline, 11 (7%) patients had a Gleason score of 3+4, while the remaining 144 (93%) patients had a Gleason score of ≤ 6. In all, 50 (32.3%) patients had disease progression on repeat biopsies, with a median progression-free survival time of 7 years. The rate of disease progression decreased after the second repeat biopsy. The 5-year overall survival rate was 100%. Having a PSA density (PSAD) of0.15 ng/mL/mL,1 positive core, and Gleason score6 at the time of the diagnosis was associated with a significantly higher rate of disease progression on univariate analysis (P0.05), while a maximum percentage of cancer in any core of10% showed a trend toward significance for a higher progression rate (P = 0.054). On multivariate analysis, only the presence of a PSAD of0.15 ng/mL/mL remained significant for a higher progression rate (P0.05). Of the 155 patients, five (3.2%) subsequently received radiotherapy, 13 (8.4%) received hormonal therapy, and 13 (8.4%) underwent radical prostatectomy.AS is a suitable management option for patients with clinically low-risk prostate cancer. A PSAD of0.15 ng/mL/mL is an important predictor for disease progression.

We report the case of a primary renal carcinoid tumor associated with a horseshoe malformation in a 43-year-old man who presented with testicular pain. The tumor was centrally located and purely solid and had features ascribed to hindgut neuroendocrine neoplasia. The relative risk of developing a carcinoid tumor in a horseshoe kidney is estimated to be x82.

Sequential bacillus Calmette-Guerin (BCG) and electromotive mitomycin (sequential therapy) have been shown in a randomized prospective trial to be superior to therapy with BCG alone in patients with high-risk non-muscle-invasive bladder cancer. The objective of the current study was to compare the costs and benefits of these 2 treatment strategies by performing a 5-year and 10-year cost-effectiveness study.A Markov model was developed to estimate the incremental cost-effectiveness ratio over a 5-year and 10-year period. Estimates of disease progression, death, and treatment efficacy were obtained from what to the authors' knowledge is the only randomized trial comparing the 2 therapies. Costs included: 1) medical costs (physician fees); 2) drug costs (preparation and instillation); and 3) hospital costs (procedure fees, admission fees, and tests and procedures done during surveillance). Patients were allowed a second course of induction therapy.Sequential therapy was found to be associated with a higher initial material cost for induction and maintenance. The average effectiveness for the patients treated with therapy with BCG alone was 4.39 years with a mean cost of $9236 (95% confidence interval, $9118-$9345) per patient. The sequential group resulted in an average effectiveness of 4.65 years, with a mean cost of $16,468 (95% confidence interval, $16,371-$16,527). The 5-year incremental cost-effectiveness ratio of sequential versus BCG-alone therapy was $27,815 per life-year gained. The corresponding figure over a 10-year period was $8618 per life-year gained.The results of the current study suggest that sequential therapy is a cost-effective treatment for patients with high-risk non-muscle-invasive bladder cancer.

Bombesin-like peptides, including the mammalian homologue gastrin-releasing peptides, are highly expressed and secreted by neuroendocrine cells in prostate carcinoma (PCa) tissues and are likely to be related to the progression of this disease. In the present study, we show that bombesin enhances the migration of androgen-independent PCa cells (PC-3) in vitro, while not affecting their adhesion to extracellular matrix proteins. The bombesin-increased motility of PC-3 cells occurs through its receptor, and, as shown with inhibitors, it likely requires activation of both protein tyrosine kinases (PTKs) and protein kinases C (PKCs). Because the focal adhesion kinase pp125FAK plays a key role in adhesion/motility and is highly expressed in advanced PCa, we examined whether in PC-3 cells bombesin signal transduction triggers the tyrosine phosphorylation of this PTK and of associated integrins and signaling proteins likely to be present in focal adhesion plaques. pp125FAK tyrosine phosphorylation was stimulated by bombesin and mimicked by PKC activation with the tumor-promotor phorbol 12-myristate-13-acetate (PMA). Moreover, this effect of bombesin on pp125FAK tyrosine phosphorylation requires the presence of both active PKC and cytoskeleton integrity since this signal was abolished by down-regulating PKCs induced by prolonged PMA treatment or by PKC inhibition with GF 109203X, as well as by disruption of the cytoskeleton with cytochalasin D. We also show that bombesin increases the tyrosine phosphorylation of a 95-kDa protein (pp95) which was co-immunoprecipitated with the αv and β (3 and 5) subunits, forming integrin receptors with αv in PC-3 cells. The protein pp95 is distinct from the endogenously tyrosine-phosphorylated β3 subunit. In addition, upon bombesin treatment, the β1, β3 and β5 integrin subunits co-immunoprecipitated with pp125FAK and major phosphotyrosine (pY)-containing proteins of 125 and 68–70 kDa, likely corresponding to pp125FAK and paxillin. Together our data suggest that, in addition to PKC activation, tyrosine phosphorylation of pp125FAK and integrin-associated proteins may play an important role in bombesin signaling, triggering the processes of PCa cell motility and invasion. Int. J. Cancer 72:498–504, 1997. © 1997 Wiley-Liss, Inc.

Study Type - Prognosis (cohort) Level of Evidence 2a. What's known on the subject? and What does the study add? Radical cystectomy with pelvic lymph node dissection is recognized as the standard of care for carcinoma invading bladder muscle and for refractory non-muscle-invasive bladder cancer. Owing to high recurrence and progression rates, a two-pronged strict surveillance regimen, consisting of both functional and oncological follow-up, has been advocated. It is also well recognized that more aggressive tumours with extravesical disease and node-positive disease recur more frequently and have worse outcomes. This study adds to the scant body of literature available regarding surveillance strategies after radical cystectomy for bladder cancer. In the absence of any solid evidence supporting the role of strict surveillance regimens, this extensive examination of recurrence patterns in a large multi-institutional project lends further support to the continued use of risk-stratified follow-up and emphasizes the need for earlier strict surveillance in patients with extravesical and node-positive disease.• To review our data on recurrence patterns after radical cystectomy (RC) for bladder cancer (BC). • To establish appropriate surveillance protocols.• We collected and pooled data from a database of 2287 patients who had undergone RC for BC between 1998 and 2008 in eight different Canadian academic centres. • Of the 2287 patients, 1890 had complete recurrence information and form the basis of the present study.• A total of 825 patients (43.6%) developed recurrence. • According to location, 48.6% of recurrent tumours were distant, 25.2% pelvic, 14.5% retroperitoneal and 11.8% to multiple regions such as pelvic and retroperitoneal or pelvic and distant. • The median (range) time to recurrence for the entire population was 10.1 (1-192) months with 90 and 97% of all recurrences within 2 and 5 years of RC, respectively. • According to stage, pTxN+ tumours were more likely to recur than ≥pT3N0 tumours and ≤pT2N0 tumours (5-yr RFS 25% vs. 44% vs. 66% respectively, P0.001). Similarly, pTxN+ tumours had a shorter median time to recurrence (9 months, range 1-72 months) than ≥pT3N0 tumours (10 months, range 1-70 months) or ≤pT2N0 tumours (14 months, range 1-192 months, P0.001).• Differences in recurrence patterns after RC suggest the need for varied follow-up protocols for each group. • We propose a stage-based protocol for surveillance of patients with BC treated with RC that captures most recurrences while limiting over-investigation.

Background. Adjunctive retroperitoneal lymphadenectomy (RPLND) plays an important role in the management of patients with metastatic nonseminomatous germ cell tumors (NSGCT). Currently, a bilateral RPLND is recommended for residual disease after chemotherapy. Methods. The authors systematically have removed all residual masses and used intraoperative frozen section analysis to dictate the extent of surgery in the patients with NSGCT. If frozen section revealed necrosis, then a limited RPLND was performed; otherwise, a bilateral RPLND was attempted. Results. Forty patients with metastatic NSGCT were studied. Of the 40 patients, 21 had necrosis identified in frozen section analysis of the residual mass(es), with 18 (85.7%) confirmed in permanent section. Two patients had microscopic viable germ cell tumor, and one had microscopic teratoma in the residual mass with the remaining RPLND specimen tumor-free. Overall, 18 of 45 patients (45%) had necrosis, 17 (42.5%) had teratoma, and 5(12.5%) had viable germ cell tumor, identified in permanent section analysis. The median follow-up period was 36 months (range, 24-60 months). Of the 40 patients, 8 (20%) experienced recurrences, although none were in the retroperitoneum; 5 were chest recurrences (4 germ cell, 1 teratoma), 2 were retrocrural recurrences (teratomas), and 1 recurrence was with liver metastasis. Of the tumors of the 21 patients with frozen section analysis showing necrosis who underwent resection of residual mass(es) and limited RPLND, 3 (14.3%) experienced recurrences; 2 had germ cell tumors in the chest, and 1 had liver metastasis. The remaining 18 (85.7%) patients had no evidence of disease, with a mean follow-up of 33 months (range, 24-60 months). Conclusions. These results suggest that in patients with metastatic NSGCT of the testis, postchemotherapy resection of all retroperitoneal masses followed by limited RPLND if frozen section analysis shows only necrosis is a safe alternative to a difficult, potentially morbid bilateral dissection.

• To investigate among general practitioners (GPs) their level of awareness and indications for urological consultations in patients treated with 5α-reductase inhibitors (5ARIs).• We conducted a survey of GPs in Quebec. • Questions covered GPs' preferred benign prostatic hyperplasia (BPH) management, knowledge of 5ARIs, their role in prostate cancer prevention, and triggers for urology consultation.• Of the surveys mailed, 599 were returned (15.7% response rate). • Therapy with 5ARIs was initiated by GPs in 34.3%, with 20% and 12% preferring 5ARIs alone and combined with an α-blocker as first-line therapy for BPH, respectively. • Once on therapy, 74% did not refer to a urologist if the PSA level did not decline after 6-12 months. • Finally, 40.7% would not advocate 5ARI chemoprevention for prostate cancer, regardless of risk reduction. • Findings were not associated with GP gender, experience or geographic location of practice (urban versus rural).• There was a preference amongst GP to use α-blockers over 5ARIs for BPH and hesitancy to use them in prostate cancer chemoprevention. • There is a lack of awareness of 5ARI effects on PSA kinetics and a reluctance to refer to a urologist. • Further education in Quebec is needed about 5ARIs to optimize their usage and avoid delaying cancer detection.

Background. This report describes an immunohistopathologic analysis characterizing the incidence, pattern of distribution, and hormonal content of neuroendocrine (NE) cells in human benign prostate and prostatic adenocarcinoma. Methods. Formaldehyde-fixed, paraffin-embedded material from 15 benign prostates, 31 primary prostatic adenocarcinomas, 16 metastatic lesions, 21 primary tumors treated with short-course diethylstilbestrol (DES), and 10 specimens from hormone-refractory patients were examined. NE cells were identified using silver histochemistry and a panel of immunohistochemical NE markers (chromogranin-A, serotonin, neuron-specific enolase), and specific peptide hormone antibodies. Results. NE cells were identified in all benign prostates. NE cells were identified in 77% of primary untreated adenocarcinomas with no significant differences with respect to pathologic stage. NE cells were found isolated and dispersed in the tumor, composing the minority of malignant cells. Double-labeling and serial section immunohistochemistry demonstrated the coexpression of prostate-specific antigen (PSA) in NE cells. In addition to serotonin, some tumors expressed multiple hormone immunoreactivities. NE cells were identified in 56% of metastatic deposits, with a similar pattern of distribution. In DES-treated cases, NE cells were found consistently in the adjacent benign epithelium, whereas 52% of tumors contained NE cells. Hormone-refractory tumors contained NE cells in 60% of cases. Conclusions. This analysis demonstrates that a significant proportion of primary and metastatic prostatic adenocarcinomas contain a subpopulation of NE cells, the expression of which does not appear to be suppressed with androgen ablation and does not correlate with pathologic stage. Furthermore, NE cells coexpress PSA, suggesting a common precursor cell of origin. The elaboration of biogenic amines and neuropeptides suggests that NE cells dispersed in prostatic carcinoma may play a paracrine growth-regulatory role.

Study Type -Therapy (case series).4.To evaluate data obtained from a large, multi-institutional, contemporary series of patients who underwent radical cystectomy (RC) in a universal healthcare system aiming to assess outcome and identify novel prognostic variables.Data were collected and pooled from 2287 patients treated with RC between 1998 and 2008 by urological oncologists from eight Canadian academic centres. Collected variables included various clinicopathological parameters, recurrence and death. Survival and prognostic variables were analyzed using the Kaplan-Meier method and Cox regression analysis.The median age of patients was 68 years with a mean (median) follow-up time of 35 (29) months. The 30, 60 and 90-day postoperative mortality rates were 1.3%, 2.6% and 3.2%, respectively. The 5-year overall, recurrence-free and cancer-specific survival was 57%, 48% and 67%, respectively, with a local recurrence rate of 6%. Pathological stage distribution waspT2N0, n = 498 (23%); pT2N0, n = 365 (17%); pT3N0, n = 463 (21%); pT4N0, n = 170 (8%); and pTxN+, n = 507 (23%). Only 3.1% of patients received neoadjuvant chemotherapy and 19.4% received adjuvant chemotherapy. On multivariate analysis, lower pathological stage, negative surgical margins, receipt of adjuvant chemotherapy, performance of pelvic lymphadenectomy and an absence of smoking were associated with prolonged disease-specific and overall survival.RC performed at academic centres provides excellent local control of disease and an acceptable clinical outcome with low perioperative mortality in patients who are treated within a universal healthcare system. Smoking, pelvic lymphadenectomy and receipt of adjuvant chemotherapy are independent prognostic factors for survival. Neoadjuvant chemotherapy continues to be under-utilized in Canada.

The Royal College of Physicians and Surgeons of Canada (RCPSC) and The American Accreditation Council for Graduate Medical Education (ACGME) general objectives mandate that all residents be competent to independently perform select surgical procedures. Unfortunately, no objective standardized measures presently exist for surgical training assessment. Operative logs have been implemented to quantify the number of cases the resident has been exposed to, however, these do not assess their degree of involvement or aptitude. An analysis of what exactly a resident performs, and how well, per case may assist in measuring their training progress. Herein, we evaluate a questionnaire to quantify the level of resident participation in radical retropubic prostatectomy (RRP) and assess whether resident perception of how much involvement in a case correlates with staff surgeons.Identical, self-administered questionnaires were distributed simultaneously to the resident and staff urologist upon completion of radical prostatectomy. The questionnaire comprised of 14 items, which were completed independently by the resident and the staff urologist. The items assessed which of the 14 specific surgical steps were actually performed by the resident. An analysis was performed to assess the level of agreement.Among all cases performed between June 2002 and July 2003, 64 RRPs performed by two surgeons had completed questionnaires by both resident and staff. Twenty-one (32.8%) cases were performed with a senior resident (R4) and 43 (67.2%) cases were performed with a chief resident (R5). Twenty (31.3%) cases involved pelvic lymph node dissection. Resident performance of key surgical steps, namely dorsal venous ligation, urethral division, lateral pedicle dissection and urethrovesical anastamosis was 59.4%, 62.5%, 84% and 59.4% respectively. Global level of agreement between staff and resident responses was 94.9% (71.4%-100%).Our results suggest that there exists good agreement between resident perception of their level of involvement in RRP and staff validation. As such, a residents' assessment of their participation is likely to be accurate. Designation of performance of key operative steps into logs may be more relevant than recording simple exposure to index cases. Attempts at measuring quality of key operative steps in the future may be beneficial.

To compare the performance of various ratios using total prostate specific antigen (PSA), complexed PSA (cPSA) and free PSA (fPSA) in the early detection of prostate cancer.The study included 535 consecutive patients evaluated at a prostate cancer detection clinic between January 1998 and October 1999. Patients had blood samples drawn before transrectal ultrasonography and prostate biopsy to measure PSA, cPSA and fPSA. Receiver operating characteristic (ROC) curves (sensitivity vs 1 - specificity) were used to evaluate the performance of PSA, cPSA, f/tPSA, cPSA/tPSA, fPSA/cPSA, tPSA/prostate volume (PV), fPSA/PV, and cPSA/PV. The areas under the curve (AUC) were calculated for each ratio. The performance of each ratio over all patients or in those with a tPSA of 4-6 or 4-10 ng/mL were evaluated.Of the 535 patients, 204 (38%) had biopsy-confirmed prostate cancer. The AUC obtained with tPSA alone was 0.64; when measured for all patients the cPSA/PV (0.78), PSA/PV (0.77), f/tPSA (0.76) and fPSA/cPSA (0.75) performed better than tPSA alone. Furthermore, in patients with a tPSA of 4-10 ng/mL, tPSA/PV (0.72), cPSA/PV (0.71), f/tPSA (0.69), fPSA/cPSA (0.69) and cPSA/tPSA (0.62) performed better than tPSA alone (0.52). Finally, in patients with a tPSA of 4-6 ng/mL, PSA/PV and cPSA/PV performed better than the other ratios.The use of PSA ratios gives a higher sensitivity and specificity for detecting prostate cancer than the use of tPSA alone.

Vascular endothelial growth factors (VEGF) figure among the most potent angiogenic factors identified. Local as well as serum VEGF-A over-expression has been correlated with metastasis in prostate cancer. However, little is known on VEGF-A expression in prostate cancer metastases themselves. Our objective was to assess VEGF-A expression in relation with angiogenesis in prostate cancer lymph node metastases.Fifty-four lymph node metastatic specimens obtained from 32 patients were included in this study. All nodes were of prostate cancer origin as confirmed by positive PSA staining. Immunohistochemistry was performed to identify VEGF-A expressing cancer cells. Consecutive sections were stained for angiogenesis using von willebrand factor (vWF) as a maker and neuroendocrine (NE) differentiation using chromogranin-A and serotonin antibodies. VEGF-A expressing cells were recorded (at 100x magnification) and expression was classified as: 1- Negative (0 cells), 2-Low (1-5 positive cells/high power field (HPF)), and 3- High (5 cells/HPF).VEGF staining was identified mainly in NE cells and endothelial cells. Of the 32 patients, VEGF expression was positive in 22 (69%), with 2 patients (6%) showing high levels and 20 patients (63%) classified as low. No VEGF expression was noted in 10 patients (31%). Of the 54 metastatic lymph node specimens examined, VEGF expression was positive in 31 (57%). VEGF-A stained NE cells did not correlate with blood vessels as revealed by vWF expression in consecutive sections (p=0.9).VEGF-A is preferentially expressed in NE cells of prostate cancer lymph node metastases and appears unrelated to angiogenesis. These observations support the role played by NE-expressing VEGF-A in the development of metastatic prostate cancer.

To provide context in oncology for the significance of the benefits and cost of combined androgen blockade (CAB) in the treatment of advanced prostate cancer.Canadian drug costs for the survival benefit with CAB in advanced prostate cancer were compared with the costs of benefit with new treatments in advanced non-small-cell lung cancer (NSCLC), metastatic colorectal cancer, and metastatic breast cancer. Clinical toxicities were also compared.The survival benefit with CAB in advanced prostate cancer appears to be approximately 3 months. The survival benefit with the addition of vinorelbine to cisplatin for the treatment of advanced NSCLC is approximately 2 months, and the survival benefit with the addition of irinotecan to fluorouracil (and leucovorin) for the treatment of metastatic colorectal cancer is approximately 2 to 3 months. The survival benefit with anastrozole or exemestane in advanced breast cancer, or with the addition of trastuzumab to standard chemotherapy in metastatic breast cancer that overexpresses human epidermal growth factor receptor 2 (HER2), is approximately 4 to 5 months. The calculated cost per month of survival benefit with bicalutamide in CAB for prostate cancer is 437 US dollars to 1107 US dollars. The cost per month of survival benefit with vinorelbine for NSCLC is 1241 US dollars and with irinotecan for colorectal cancer is 6812 to 11,214 US dollars. The calculated cost per month of survival benefit with anastrozole for breast cancer is 170 US dollars, for exemestane is 185 US dollars, and the cost per month with the addition of trastuzumab is 5230 US dollars. Vinorelbine and irinotecan are associated with severe grade 3 or 4 clinical toxicities, and an increased frequency of heart failure has been observed when trastuzumab is added to anthracyclines. Anastrozole, exemestane and nonsteroidal antiandrogens are associated with mild to moderate side effects.The advantages offered by CAB (including the cost per month of survival benefit and minimal associated clinical toxicities) are comparable to the reported advantages of new treatments for other common cancers such as NSCLC, colorectal cancer, and breast cancer.

We assessed familial prostate and breast cancer in Quebec.Using a self-administered mail survey we assessed the prevalence of prostate and breast cancer in first degree relatives of 1,633 men treated with prostatectomy for prostate cancer in the province of Quebec and in first degree relatives of 1,386 spouse controls.The OR of familial breast cancer was 1.1 (95% CI 0.9 to 1.4). The OR of 3.0 (95% CI 2.5 to 3.6) recorded for prostate cancer was modified by francophone versus anglophone linguistic preference (OR 3.2, 95% CI 2.6, 3.9 versus 1.5, 95% CI 0.8 to 2.7, p = 0.02). Male sibship size was a statistically significant parameter modifying this association (p = 0.02), namely no brothers (OR 1.7, 95% CI 1.0 to 2.8), 1 or 2 (OR 3.1, 95% CI 2.2 to 4.3) and 3 or more (OR 3.9, 95% CI 2.9 to 5.2). Geographic regions of the province including and neighboring greater Montreal showed a lower OR than more peripheral regions (2.5, 95% CI 2.0 to 3.2 versus 4.1, 95% CI 2.9 to 5.7, p = 0.02).Francophone men with large male sibships residing in remote areas may be at higher risk for familial prostate cancer and represent the ideal target for further efforts to determine the genetic component of prostate cancer in Quebec.

Laboratory and epidemiological studies suggest that high circulating insulin-like growth factor (IGF)-1 and low IGF binding protein-3 are associated with increased prostate cancer risk. However, the usefulness of serum IGF-1 or IGF binding protein-3 for predicting pathology results in men undergoing prostate biopsy is unclear. We examined the relationships of serum IGF-1, IGF binding protein-3 and the results of prostate biopsy.A total of 652 consecutive patients with elevated serum prostate specific antigen (PSA) or abnormal digital rectal examination who were referred for transrectal ultrasound sextant prostate needle biopsy underwent blood sampling before biopsy. PSA, free PSA, IGF-1 and IGF binding protein-3 were measured. There were 244 men (37.4%) with cancer and 408 controls with benign conditions.Mean IGF-1 plus or minus SD in the cancer and control groups was 176.1 +/- 58.3 and 178.7 +/- 54.7 ng./ml., respectively (p = 0.57). Mean IGF binding protein-3 in the cancer and control groups was 2,724 +/- 647 and 2,673 +/- 589 ng./ml., respectively (p = 0.3). Adjustment for age and PSA showed significantly lower IGF-1 in cancer cases, while IGF binding protein-3 was not significant. ROC values were significantly higher for free-to-total PSA and PSA than for crude and age adjusted IGF-1 and IGF binding protein-3.Our data indicate that serum IGF-1 or IGF binding protein-3 does not predict the results of prostate biopsy in men with elevated PSA or abnormal digital rectal examination. This finding implies that while there is evidence that the IGF-1 level is a risk factor for prostate cancer, neither IGF-1 nor IGF binding protein-3 can be used as a tumor marker for this disease.

Clinical outcomes in patients with localized prostate cancers are heterogeneous. In recent years, analyses of large datasets from multiple centres have yielded a better understanding of how to measure risk in localized prostate cancer. Regardless of whether patients are treated with prostatectomy, radiotherapy, brachytherapy, or expectant management, three factors appear correlated with clinical outcome: biopsy Gleason score, clinical T stage, and serum prostate-specific antigen (PSA). Partin Tables, derived from these parameters and recently updated and refined, may be used to estimate the risk of metastasis and to assess certain aspects of surgical management in clinically localized disease. Partin tables, however, are limited by the fact that pathologic stage does not always predict clinical outcome. Nomograms that employ serum PSA, biopsy Gleason score, and clinical T-stage have been developed with the aim of predicting clinical recurrence after radical prostatectomy or radiation therapy. Three risk categories for clinically localized prostate cancer have recently been developed by the Canadian Genito-Urinary Radiation Oncologists Consensus Conference, which group cases according to serum PSA, T-stage, and biopsy Gleason score. Additional factors have been assessed in the hopes of improving the prediction of outcome in clinically localized disease, but none of these has consistently been demonstrated to add independent value to the principal parameters of serum PSA, T-stage, and Gleason score. Virtually all predictive nomograms, algorithms, and tables incorporate a combination of these three parameters. While these tools may be useful in prognosticating an individual case, several limitations preclude their widespread use. The greatest benefit to date of risk stratification is its use in comparing outcomes of series of patients treated with various modalities, and in clinical trial design and analysis.

Our patient had neglected a growing left testicular mass over a 5-year period. Due to the large size of the tumor a scrotal delivery was necessary. Pathology showed a 1.6 kg pure classic seminoma. Metastatic work up revealed stage IIC disease and he was treated with primary cisplatin-based chemotherapy and remains free of recurrence after 24 months. The potential risk of scrotal violation is discussed.

The management of muscle-invasive transitional cell carcinoma (TCC) of the bladder continues to evolve. The standard treatment for patients presenting with clinical stage T2-4aN0M0 bladder cancer remains radical cystectomy. However, the management of patients who present with more advanced disease on clinical evaluation, such as unresectable pelvic tumor (T4b) or regional pelvic lymph node metastases (N+) remains unclear. In addition, the intraoperative management of unsuspected pelvic adenopathy identified during exploration of a planned radical cystectomy, continues to generate controversy. The following discussion relates to the evolving attitudes towards the role of surgery in the treatment of advanced bladder cancer.

The pathogenesis of primary renal carcinoid tumor is unknown. One hypothesis has implied derivation from a yet unrecognized intrinsic neuroendocrine cell in the renal parenchyma/hilum either as a minute endocrineparacrine constituent or resulting from entrapped/misplaced progenitor cells of the so-called dispersed neuroendocrine system during organogenesis. Immunohistochemical staining for chromogranin and serotonin was systematically performed on a whole-mount and geographically mapped normal adult kidney, kidneys from 15 fetuses (age range: 15 to 38 weeks), and renal specimens from 18 infants/children (age range: 7 days to 123 months). Minute paraganglion nests (composed of chromogranin positive/serotonin negative chief cells and S-100 protein positive dendritic cells) were incidentally detected within the renal hilum primitive stroma (unilaterally) of two fetuses at 22 and 26 weeks. Sequestration and persistence of such paraganglion nests during renal growth and maturation would offer a basis for the rare occurrence of extra-adrenal paraganglioma involving the renal hilum/pedicle. Otherwise, no neuroendocrine cell was detected within the renal parenchyma or hilum, therefore not validating/sustaining the aforementioned hypothesis in the pathogenesis of renal carcinoid tumor.

We report the case of a primary renal carcinoid tumor associated with a horseshoe malformation in a 43-year-old man who presented with testicular pain. The tumor was centrally located and purely solid and had features ascribed to hindgut neuroendocrine neoplasia. The relative risk of developing a carcinoid tumor in a horseshoe kidney is estimated to be x82.

The objective of this study was to characterize the calcium mobilizing activity of bombesin-related neuropeptides in PC-3 cells.Intracellular free Ca2+ concentration ([Ca2+]i) was measured following the administration of bombesin-related neuropeptides using spectrofluorometric monitoring of PC-3 cells loaded with Fura2/AM.Individual neuropeptides induced a rapid rise in [Ca2+]i immediately after stimulation in similar fashion. When two different peptides were administered simultaneously, the [Ca2+]i changes were similar to that produced by each peptide alone. However, simultaneous addition of tyr4-bombesin 100 nM and 2% serum resulted in [Ca2+]i increase greater than either alone. Sequential stimulation by same or different peptides, was not able to induce another response. However, 6 hrs after the first stimulus, a second stimulus was able to induce a similar response.The data indicate that all members of the bombesin-related family of neuropeptides are capable of triggering calcium mobilization in PC-3 cells via a similar signalling pathway. PC-3 cells become acutely desensitized to additional stimulation of neuropeptide. This desensitization is selective and reversible, requiring approximately 6 hrs for recovery.

OBJECTIVE: The objective of this study was to determine the benefit of repeat transrectal ultrasound-guided prostatic biopsy (TRUSBx) among men with prior benign histology on digitally guided biopsy despite suspicious digital rectal examination (DRE) findings. PATIENTS AND METHODS: From January 1, 1990 to May 30, 1993, we evaluated 130 consecutive men, referred to us with benign pathology on digitally-guided biopsy and DRE suspicious of cancer. All patients underwent systematic and directed TRUSBx. RESULTS: TRUSBx detected previously undiagnosed malignancy in 67 cases (51%). CONCLUSION: It is mandatory to reevaluate by TRUSBx, all patients with a palpable abnormality on DRE and a prior benign pathology on digitally-guided biopsy, as the likelihood of finding cancer is elevated.

pp125FAK, a protein tyrosine kinase (PTK) co-localized with integrins in focal adhesion plaques, is known to transduce signals involved in the regulation of cell adhesion and motility as well as the anchorage-independent growth of transformed cells. We investigated whether pp125FAK could be part of a signalling pathway that contributes to the progression of human prostate carcinoma (PCa). Up-regulation of pp125FAK expression, its activation by phosphorylation on tyrosine and its association with paxillin and p50csk were preferentially observed in PCa tissues from patients with metastases, whereas normal and hyperplastic prostates and localized PCa tissues showed undetectable or low levels of both FAK mRNA and protein and an absence of pp125FAK signalling complexes. The increase in expression and activation of pp125FAK in metastatic PCa tissues was also corroborated by our findings in human PCa cell lines. Indeed, higher levels of pp125FAK and FAK mRNA were observed in highly tumorigenic PC-3 cells as was the presence of activated pp125FAK, as opposed to an inactive form in LNCaP cells, which have a lower tumorigenic ability. In addition, pp125FAK formed signalling complexes with both paxillin and p50csk in PC-3 cells as in metastatic PCa tissues. Together, our results show that an increase in FAK mRNA and protein, as well as pp125FAK activation and association with signalling proteins, correlates with progression and invasion in human PCa tissues and cells.

OBJECTIVE: To reassess PSA density (PSAD) in the detection of non-palpable, isoechoic prostate cancer and to analyze the effect of potentially inaccurate non-planimetric transrectal ultrasound volume estimates on the diagnostic performance of this diagnostic tool. METHODS: We prospectively evaluated 343 consecutive men with non-suspicious digital rectal examination and transrectal ultrasound findings and with serum PSA in the intermediate range (4.1-10 ng/mL). All men underwent systematic sextant biopsies of the peripheral zone. We performed a two-fold analysis of PSAD performance first using measured gland volume and then using modified gland volumes ranging from a 25% underestimation to a 25% overestimation, in 5% stepwise increments. RESULTS: With a 0.15 PSAD cut-off, we would have missed 14, 34 and 48% of cancers, if we had respectively used a volume underestimate of 25%, the measured volume and a volume overestimate of 25%. CONCLUSIONS: Potential gland volume under- or overestimation may substantially affect the diagnostic performance of PSAD. Although PSAD may represent a useful adjunct in the early detection of prostate cancer, it may compromise cancer detection in a substantial proportion of cases, if used as the only indicator for biopsy.

Parapelvic cysts in children, adolescents and young adults are rare. We report the case of an asymptomatic nineteen year old male with a large parapelvic cyst causing obstruction and distortion of the pelvocalyceal system.

Prostate adenocarcinoma is predominantly a disease of older men. Males younger than 50 years account for 1% of all patients with prostate cancer. The authors retrospectively examined cases of prostate adenocarcinoma in patients younger than 50 years of age to determine the natural history and prognosis of this malignancy in the younger population.The medical records of 151 patients were reviewed, with particular attention to age and year at diagnosis, race, symptoms at presentation, family history of prostate cancer, histologic grade, clinical and pathologic stage, treatment modality, and clinical outcome.Univariate analyses demonstrated a significant correlation between higher disease stage (P = 0.0001), higher tumor grade (P = 0.0001), earlier year of diagnosis (P = 0.01), symptoms at presentation (P = 0.0001), and race (P = 0.01) with shorter disease-specific survival. However, multivariate analysis revealed that only stage and grade were statistically significant predictors for poor prognosis after controlling for other variables. With a one-unit increase of stage or grade, the risk of death from disease increases 2.2 or 1.9 times, respectively.These data suggest that patients younger than 50 years with prostate cancer present with similar symptomatology, histologic grade, and disease stage as the older population. Patients with disease confined to the prostate have a relatively good disease-specific survival but remain at risk for death even 15 years after diagnosis. When carcinoma escapes the confines of the prostate, the prognosis is uniformly poor.

Adjunctive retroperitoneal lymphadenectomy (RPLND) plays an important role in the management of patients with metastatic nonseminomatous germ cell tumors (NSGCT). Currently, a bilateral RPLND is recommended for residual disease after chemotherapy.The authors systematically have removed all residual masses and used intraoperative frozen section analysis to dictate the extent of surgery in the patients with NSGCT: If frozen section revealed necrosis, then a limited RPLND was performed; otherwise, a bilateral RPLND was attempted.Forty patients with metastatic NSGCT were studied. Of the 40 patients, 21 had necrosis identified in frozen section analysis of the residual mass(es), with 18 (85.7%) confirmed in permanent section. Two patients had microscopic viable germ cell tumor, and one had microscopic teratoma in the residual mass with the remaining RPLND specimen tumor-free. Overall, 18 of 45 patients (45%) had necrosis, 17 (42.5%) had teratoma, and 5 (12.5%) had viable germ cell tumor, identified in permanent section analysis. The median follow-up period was 36 months (range, 24-60 months). Of the 40 patients, 8 (20%) experienced recurrences, although none were in the retroperitoneum; 5 were chest recurrences (4 germ cell, 1 teratoma), 2 were retrocrural recurrences (teratomas), and 1 recurrence was with liver metastasis. Of the tumors of the 21 patients with frozen section analysis showing necrosis who underwent resection of residual mass(es) and limited RPLND, 3 (14.3%) experienced recurrences; 2 had germ cell tumors in the chest, and 1 had liver metastasis. The remaining 18 (85.7%) patients had no evidence of disease, with a mean follow-up of 33 months (range, 24-60 months).These results suggest that in patients with metastatic NSGCT of the testis, postchemotherapy resection of all retroperitoneal masses followed by limited RPLND if frozen section analysis shows only necrosis is a safe alternative to a difficult, potentially morbid bilateral dissection.

Radical prostatectomy is an excellent form of treatment of pathologically organ-confined prostatic carcinoma. However, most clinically localized prostatic cancers have pathologic evidence of extracapsular spread, limiting the effectiveness of radical surgery in curing this disease. To improve the organ-confined rate of prostate cancer, we studied the effect of preoperative or neoadjuvant androgen deprivation therapy (ADT). Our initial attempts focused on downstaging locally advanced tumors (T3) with neoadjuvant diethylstilbestrol (3 mg/d). Our study of 59 patients revealed that although there were significant clinical signs of downstaging, most patients still had extraprostatic disease. However, a subset of patients demonstrated marked pathologic regression, so we initiated a nonrandomized but controlled study of neoadjuvant ADT (goserelin acetate and flutamide for 3 months) followed by radical prostatectomy in patients with clinically localized prostate cancer. Of 72 control and 69 study patients, the rate of organ-confined disease was 48% and 74% (including 4% with no detectable residual carcinoma), respectively. In addition, the margin-positive rate was 33% and 10%, respectively. As demonstrated in the previous study, changes in serum prostate-specific antigen, transrectal ultrasonographic evaluations, and digital rectal examinations could not predict those patients with favourable pathology. Our results suggest that neoadjuvant ADT may improve the pathologic stage in some prostatic carcinomas and is worthy of further investigation in the efforts to augment the effectiveness of radical prostatectomy.

This report describes an immunohistopathologic analysis characterizing the incidence, pattern of distribution, and hormonal content of neuroendocrine (NE) cells in human benign prostate and prostatic adenocarcinoma.Formaldehyde-fixed, paraffin-embedded material from 15 benign prostates, 31 primary prostatic adenocarcinomas, 16 metastatic lesions, 21 primary tumors treated with short-course diethylstilbestrol (DES), and 10 specimens from hormone-refractory patients were examined. NE cells were identified using silver histochemistry and a panel of immunohistochemical NE markers (chromogranin-A, serotonin, neuron-specific enolase), and specific peptide hormone antibodies.NE cells were identified in all benign prostates. NE cells were identified in 77% of primary untreated adenocarcinomas with no significant differences with respect to pathologic stage. NE cells were found isolated and dispersed in the tumor, composing the minority of malignant cells. Double-labeling and serial section immunohistochemistry demonstrated the coexpression of prostate-specific antigen (PSA) in NE cells. In addition to serotonin, some tumors expressed multiple hormone immunoreactivities. NE cells were identified in 56% of metastatic deposits, with a similar pattern of distribution. In DES-treated cases, NE cells were found consistently in the adjacent benign epithelium, whereas 52% of tumors contained NE cells. Hormone-refractory tumors contained NE cells in 60% of cases.This analysis demonstrates that a significant proportion of primary and metastatic prostatic adenocarcinomas contain a subpopulation of NE cells, the expression of which does not appear to be suppressed with androgen ablation and does not correlate with pathologic stage. Furthermore, NE cells coexpress PSA, suggesting a common precursor cell of origin. The elaboration of biogenic amines and neuropeptides suggests that NE cells dispersed in prostatic carcinoma may play a paracrine growth-regulatory role.