Prostatic Urothelial Carcinoma Research Articles

Primary high-grade urothelial carcinoma of prostate with prostatic hyperplasia: a rare case report and review of the literature

Background Primary urothelial carcinoma in the prostate (UCP) is extremely rare and occurs most frequently in the bladder. There are only dozens of primary cases reported in the literature. Here, we describe a rare case of primary UCP and review the literature. Case presentation A 67-year-old widowed male, was referred to our hospital due to the frequency, and urgency of dysuria. Magnetic resonance imaging (MRI) examination revealed prostate size was about 57 mm × 50 mm × 54 mm, increased prostatic transitional zone, and surrounding of prostatic duct indicate bar isointense T1, short T2, hyperintense DWI, and hyposignal ADC (PI-RADS 3); posterior of peripheral zone indicate patchy isointense T1, short T2, hyperintense DWI, and hyposignal ADC (PI-RADS 5). Subsequently, the patient underwent a transrectal prostate biopsy. Histopathological and immunohistochemical (IHC) assessments showed prostatic high-grade urothelial carcinoma with benign prostatic hyperplasia. Finally, the patient underwent laparoscopic radical prostatectomy. Four months after surgery, CT plain and enhanced scan revealed thickening of the bladder wall. On further workup, cystoscopy revealed lymphoid follicular changes in the cut edge of the radical prostatectomy, and cystoscopic biopsies showed the malignant tumor. Conclusions Prostatic urothelial carcinoma should always be considered if the patient with severe lower urinary tract symptoms or hematuria, PSA, and digital rectal examination without abnormalities, without a personal history of urothelial cancer, but contrast-enhanced MRI showed the lesion located in the prostate. As of right now, radical surgical resections remain the most effective treatment. The effectiveness of neoadjuvant or adjuvant chemotherapy is still controversial.

Urothelial carcinoma of the prostate with raised β-hCG levels: a case report

BackgroundTrophoblastic differentiation in primary urothelial carcinoma of the prostate is extremely rare. An increased level of β-subunit human chorionic gonadotropin in serum in urothelial carcinoma is detected in approximately 30% of cases. To our knowledge, increased concentration of β-subunit human chorionic gonadotropin in serum in prostatic urothelial carcinoma has never been reported and its clinical significance is not evaluated yet.Case reportHere we present the case of a 67-year-old European patient who was admitted to the hospital with hematuria, dysuria, and enlarged painful testis. Ultrasonographic examination of the testis did not reveal any focal lesion. Magnetic resonance imaging of the pelvis showed a tumor of 62 mm diameter mainly located in the posterior part of the prostatic gland. A pathological examination from cystoscopy biopsy allowed us to set the diagnosis of high-grade invasive urothelial carcinoma with trophoblastic differentiation. The patient received neoadjuvant treatment. Nonetheless, after a short period of disease stabilization, he developed progression and brain metastasis. He died 9 months after diagnosis. During the disease course, his β-human chorionic gonadotropin level was measured repeatedly and analyzed in relation to disease progression. The level of serum β-human chorionic gonadotropin corresponded with the therapy response; it was at its lowest during stabilization and the highest in the metastatic stage.ConclusionOur case study provides the first report of urothelial cancer of the prostate, with a concomitant increase of β-subunit human chorionic gonadotropin level with testis enlargement. Besides its rarity, it constitutes an interesting observation of increasing β-subunit human chorionic gonadotropin concentration with concomitant disease progression.

Temporal changes in the screening, diagnosis and surgical treatment of genitourinary (GU) malignancies during the COVID-19 pandemic.

281 Background: The COVID-19 pandemic has been associated with a significant disruption in healthcare services including cancer screening and diagnosis. Delays in cancer screening and treatment may lead to increased mortality. We aimed to analyze changes in screening, diagnosis and surgical treatment of common GU malignancies in relation to the COVID-19 pandemic. Methods: We evaluated screening, novel diagnoses, and surgical management modalities of prostate cancer (PCa), urothelial carcinoma (UC) and renal cell carcinoma (RCC) within Massachusetts General Brigham, the largest healthcare system in the Northeastern United States, over four 3-month time periods during the pandemic (March 2020- March 2021). The percentage change in screening, diagnoses and management modalities during pandemic periods as compared to the immediate pre-pandemic period (December 2019-March 2020) was calculated as (Nperiod – Ncontrol)/Ncontrol. The difference in “predicted” versus “observed” diagnoses in each pandemic period was compared to the average of the four preceding 3-month periods (March 2019-March 2020) to account for seasonal variation. Results: The first pandemic peak (March-June 2020) was associated with a significant decline across screening, diagnosis and treatment, ranging from -15.7 to -64.8%, followed by a progressive recovery, ranging from -5.9 to +25.1% in the latest period (December 2020-March 2021) (Table). Although 725 diagnoses were “missed“ between March and June 2020 as compared to the previous 12 months, 971 diagnoses were “recovered” between June 2020 and March 2021. Conclusions: A substantial disruption in the screening, diagnosis and treatment of GU malignancies was observed early in the pandemic, followed by a progressive rebound and recovery. The highest declines were observed for PSA screening, and the lowest for cystectomy procedures, reflecting triaging of care based on severity during the pandemic.[Table: see text]

A clinico-histopathological spectrum of Prostatic lesions at a tertiary care teaching institute

: Prostatic carcinoma is the second most common cause of cancer deaths in men and the incidence is increasing significantly in recent years, due to early screening measures. A study designed to identify the prostatic lesions spectrum as per histopathological classification.: 50 prostatic lesion samples collected in 10% formalin were subjected to H and E stain and the mean AgNOR counts were calculated.: Out of 50 specimens, 80% were benign and 20% belongs to malignancy. The mean age of patient’s benign and malignant lesions is 63.5 ± 9.2 years and 69.5 ± 8.5 years respectively (P=0.09). The most common clinical symptom of benign lesions was frequency in35 patients, followed by hesitancy and nocturia in 33 and 30 patients respectively. Serum PSA values above 10ng/ml were seen in 10 benign cases and 5 malignant cases (P=0.02). Out of 50 cases, 35 were BPH, 5 were non-specific granulomatous prostatitis, 8 prostatic adenocarcinoma, 1 case urothelial carcinoma and 1case with both prostatic adenocarcinoma and urothelial carcinoma were recorded. High grade PIN identified in 9 specimens and low grade PIN identified in 8 specimens. High grade PIN shows association with adenocarcinoma. Basal cell hyperplasia identified in 3 specimens. Tufting Pattern was observed in 2 specimens, flat Pattern observed in 4 specimens, and cribriform pattern observed in 1 specimen out of 9. Majority of patients diagnosed as conventional adenocarcinoma with a score of 9 (3 cases) followed by score of 8 (2 cases).: BHP is the most common non neoplastic prostate lesion, and commonly encountered in age group of 60- 70 years. In the current scenario, histopathological analysis of prostate specimens plays crucial role in both diagnosis and management.

Can frozen-section analysis of ureteric margins at the time of radical cystectomy predict upper tract recurrence?

ABSTRACT Objective To summarise the currently available literature and analyse available results of the outcome of intraoperative frozen-section analysis (FSA) on upper urinary tract recurrence (UUTR) after radical cystectomy (RC). Materials and methods A systematic review of the literature was performed according to the Cochrane Reviews guidelines and in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Articles discussing ureteric FSA with RC were identified. Results The literature search yielded 21 studies, on which the present analysis was done. The studies were published between 1997 and 2019. There were 10 010 patients with an age range between 51 and 95 years. Involvement of the ureteric margins was noted in 2–9% at RC. The sensitivity and specificity of FSA were ~75% and 99%, respectively. Adverse pathology on FSA and on permanent section, prostatic urothelial carcinoma involving the stroma but not prostatic duct, and ureteric involvement on permanent section were all more likely to develop UUTR. Neither evidence of ureteric involvement nor ureteric margin status on permanent section were significant predictors of overall survival. Conclusion Routine FSA is mandatory for a tumour-free uretero–enteric anastomosis and is predictive of UUTR. To lower the UUTR, FSA is not necessary if the ureters are resected at the level where they cross the common iliac vessels. FSA is indicated whenever the surgeon encounters findings suspicious of malignancy, e.g. ureteric obstruction, periureteric fibrosis, diffuse carcinoma in situ, induration or frank tumour infiltration of the distal ureter is discovered unexpectedly during surgery, and prostatic urethral involvement. Abbreviations CIS: carcinoma in situ; FSA: frozen-section analysis; HR: hazard ratio; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RC: radical cystectomy; (UT)UC: (upper tract) urothelial carcinoma; UUT(R): upper urinary tract (recurrence)

MP54-19 IMPACT OF PROSTATE INVOLVEMENT ON OUTCOMES IN PATIENTS TREATED WITH RADICAL CYSTOPROSTATECTOMY FOR BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Invasive IV1 Apr 2017MP54-19 IMPACT OF PROSTATE INVOLVEMENT ON OUTCOMES IN PATIENTS TREATED WITH RADICAL CYSTOPROSTATECTOMY FOR BLADDER CANCER Marco Moschini, Andrea Gallina, Giusy Burgio, Paolo Dell'Oglio, Emanuele Zaffuto, Agostino Mattei, Rocco Damiano, Shahrokh Shariat, Vincenzo Mirone, Andrea Salonia, Alberto Briganti, Francesco Montorsi, and Renzo Colombo Marco MoschiniMarco Moschini More articles by this author , Andrea GallinaAndrea Gallina More articles by this author , Giusy BurgioGiusy Burgio More articles by this author , Paolo Dell'OglioPaolo Dell'Oglio More articles by this author , Emanuele ZaffutoEmanuele Zaffuto More articles by this author , Agostino MatteiAgostino Mattei More articles by this author , Rocco DamianoRocco Damiano More articles by this author , Shahrokh ShariatShahrokh Shariat More articles by this author , Vincenzo MironeVincenzo Mirone More articles by this author , Andrea SaloniaAndrea Salonia More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , and Renzo ColomboRenzo Colombo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1691AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The impact of the different types of prostate involvement by urothelial carcinoma (PUC) or prostate adenocarcinoma (PCa) at the time of radical cystoprostatectomy (RCP) has not been fully investigated. METHODS Data from 893 male patients treated with RCP and pelvic lymph node dissection at a tertiary referral center for nonmetastatic bladder cancer between 1992 and 2012 were assessed. Significant PCa was defined as extracapsular disease and/or Gleason Score = 7. Prostatic urothelial carcinoma (PUC) was stratified as stromal versus urethral/duct involvements. Multivariable Cox regression analyses were built to test the impact of the presence of incidental PCa and PUC on outcomes. RESULTS PCa was present in 319 (35.7%) patients, of which 45 (14.1%) had significant disease. While, the proportion of significant PCa did not change significantly (p=0.8), the rate of indolent PCa increased from 17.1%, to 29.4% to 37.9%, respectively (p<0.001). PUC was identify in 181 patients (20%): 75 (41.1%) with urethral/duct involvement and 106 (58.6%) with stromal. Within a median follow-up of 72 months, stromal PUC, but not the other forms of PUC or PCa, was associated with disease recurrence and cancer-specific mortality. In multivariable analyses adjusted for the effects of standard features, stromal PUC remained associated with recurrence (Hazard Ratio [HR]:2.01, p=0.03) cancer-specific mortality (HR: 1.65, p=0.01) and overall mortality (HR: 1.45, p=0.03). CONCLUSIONS PCa involvement does not affect outcomes in patients treated with RCP for bladder cancer. Conversely, prostatic stromal invasion with urothelial carcinoma confers a poor survival confirming its aggressiveness. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e729 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Marco Moschini More articles by this author Andrea Gallina More articles by this author Giusy Burgio More articles by this author Paolo Dell'Oglio More articles by this author Emanuele Zaffuto More articles by this author Agostino Mattei More articles by this author Rocco Damiano More articles by this author Shahrokh Shariat More articles by this author Vincenzo Mirone More articles by this author Andrea Salonia More articles by this author Alberto Briganti More articles by this author Francesco Montorsi More articles by this author Renzo Colombo More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Impact of Prostate Involvement on Outcomes in Patients Treated with Radical Cystoprostatectomy for Bladder Cancer

Objective: The study aimed to evaluate the impact of the different types of prostate involvement at the time of radical cystoprostatectomy (RCP). Methods: Data from 893 male patients treated with RCP at a referral center for bladder cancer (BCa) were assessed. Prostatic urothelial carcinoma (PUC) was stratified as stromal vs. urethral/duct involvements. Multivariable Cox regression analyses were built to test the impact of the presence of incidental prostate cancer (PCa) and PUC on survival outcomes. Results: PCa was present in 319 (35.7%) RCP patients, of which 45 (14.1%) had significant PCa disease. PUC was identified in 181 patients (20%): 75 (41.1%) with urethral/duct involvement and 106 (58.6%) with stromal. Within a median follow-up of 72 months, stromal PUC, but not the other forms of PUC or PCa, was associated with worse survival outcomes. In multivariable analyses adjusted for the effects of standard features, stromal PUC remained associated with recurrence (hazards ratio [HR] 2.01, p = 0.03), cancer-specific mortality (HR 1.65, p = 0.01), and overall mortality (HR 1.45, p = 0.03). Conclusion: Prostatic stromal invasion with urothelial carcinoma confers a poor survival expectation to BCa patients after surgical treatment. Conversely, other type of urothelial prostatic invasions or the presence of concomitant PCa does not seem to be associated with differences in survival outcomes.

Undiagnosed prostatic malignancy at the time of radical cystoprostatectomy after prior prostatic radiation therapy.

Purpose:We determined the prevalence of prostatic malignancy in patients undergoing radical cystoprostatectomy (RC) for urothelial carcinoma (UC) with a history of radiation therapy (XRT) treatment for prostatic adenocarcinoma (PCa).Materials and Methods:Fifty-three men who underwent a RC for UC that were previously treated for PCa with XRT were retrospectively identified. Pathology reports were reviewed to assess for residual PCa or prostatic UC at the time of surgery.Results:Thirteen (25%) patients had residual PCa, 16 (30%) had prostatic UC, and 8 (15%) had both. Sixteen (30%) patients had no evidence of prostatic disease. Patients with PCa had median tumor volume of 2.2 cc (interquartile range: 1.2–2.5 cc) and one-third had high-risk features (Gleason score >8 or pT3-T4 disease). Sixteen of 24 patients (67%) with prostatic UC had a stromal invasion, 5 (21%) had a ductal invasion, and 3 (13%) had carcinoma in situ. Tumors at bladder neck or trigone during transurethral resection were predictive of prostatic UC (odds ratio: 4.32, 95% confidence interval: 1.2–15.5, P = 0.025).Conclusions:Despite prior XRT for PCa, less than one-third of patients had no prostatic disease at the time of RC. Routine prostatic sampling should be considered in these patients especially if considering the orthotopic diversion.

The prevalence and risk factors for synchronous prostate carcinoma and urothelial carcinoma: Experience in CCH

The prevalence and risk factors for synchronous prostate carcinoma and urothelial carcinoma: Experience in CCH

Incidental prostate cancer in Asian men: high prevalence of incidental prostatic adenocarcinoma in Chinese patients undergoing radical cystoprostatectomy for treatment of bladder cancer and selection of candidates for prostate-sparing cystectomy.

Previous studies report a low prevalence of incidental prostate cancer in Chinese patients (3-7%). We evaluated incidental prostatic adenocarcinoma (PCa) and urothelial carcinoma (UCa) involvement of the prostate in cystoprostatectomy specimens. We analyzed 340 cystoprostatectomy specimens from patients who underwent radical cystoprostatectomy for the treatment of bladder cancer in China from 2004 to 2014. None of the patients had known prostate cancer prior to cystoprostatectomy. Overall, 180 (53%) patients had either PCa or UCa in the prostate. We found that 95 (28%) had PCa and 115 (34%) had UCa involvement of prostate. The rate of incidental prostate cancer was 21% and 31%, respectively, from two study periods (2004-2008 and 2009-2014). Among the 95 patients with PCa, 19 (20%) had Gleason score of ≥7, nine (10%) had PCa tumor volume >0.5 cc, and eight (8.4%) had extracapsular extension. Of the 115 with prostatic UCa, 61 had prostatic urethra and/or periurethral prostatic duct involvement only, while 54 had prostatic stromal invasion. Age (odds ratio [OR] = 1.04, P = 0.001), increasing stage of bladder tumor (OR = 1.28, P = 0.005), multifocal tumors of bladder (OR = 3.22, P < 0.001), carcinoma in situ (CIS) in the bladder (OR = 5.52, P < 0.001), and bladder neck involvement (OR = 6.12, P < 0.001) were strongly associated with prostatic UCa. The rate of incidental PCa in cystoprostatectomy specimens in China has increased over the last decade. Patients with advanced age, elevated serum PSA level, advanced bladder tumor stage, multifocal bladder tumors, CIS in the bladder, and tumor location at the bladder neck should be excluded as candidates for prostate-sparing cystectomy.

Urothelial carcinoma involving the prostate: the association of revised tumour stage and coexistent bladder cancer with survival after radical cystectomy

To evaluate survival among patients with urothelial carcinoma (UC) within the prostate in order to assess the impact of depth of tumour invasion as well as the importance of a concurrent bladder tumour. We identified 201 patients who underwent radical cystectomy (RC) between 1980 and 2006 and were found to have UC involving the prostate. All specimens were re-reviewed by a genitourinary pathologist. Survival was estimated using the Kaplan-Meier method and compared with the log-rank test. Cox hazard regression models tested the association of clinicopathological variables with outcome. In all, 93 patients had pTis disease in the prostate, 43 had pT2 tumours, and 66 patients were pT4a. The median follow-up was 10.5 years. The 5-year cancer-specific survival for patients with pTis, pT2, and pT4a prostate UC was 73%, 57%, and 21% respectively (P < 0.001). On multivariable analysis, higher prostate tumour stage (hazard ratio [HR] 2.09; P = 0.01), positive lymph node status (HR 2.09; P = 0.002), and concurrent ≥pT3 bladder cancer (HR 4.16; P < 0.001) were significantly associated with an increased risk of death from UC. Among patients with prostatic UC involvement, depth of tumour invasion was significantly associated with cancer-specific mortality, validating the staging reclassification. Concurrent locally advanced bladder cancer also negatively impacted survival, suggesting the potential prognostic value of reporting a secondary tumour stage in such cases.

Usefulness of Transurethral Biopsy for Staging the Prostatic Urethra before Radical Cystectomy

We determined the likelihood that transurethral resection biopsy of the prostatic urethra adjacent to the verumontanum would detect prostatic involvement of urothelial carcinoma in patients with bladder carcinoma. We compared precystectomy transurethral resection biopsy specimens of the prostatic urethra with those of the matched radical cystoprostatectomy in 272 patients with urothelial carcinoma of the bladder. All prostates were evaluated by whole mount step sections. Prostatic involvement by urothelial carcinoma was detected by transurethral resection biopsy or radical cystoprostatectomy in 101 patients (37.1%). Transurethral resection biopsy detected urothelial carcinoma in 72 cases with 71.3% sensitivity and 100% specificity. The overall accuracy of transurethral resection biopsy to detect urothelial carcinoma of the prostate was 89% (positive and negative predictive values 100% and 86%, respectively). Invasive prostatic urothelial carcinoma arising from the prostatic urethra was detected by transurethral resection biopsy in 21 of 26 patients (81%) while prostatic carcinoma in situ was detected in 39 of 52 (75%). Transurethral resection biopsy detected prostatic invasive urothelial carcinoma resulting from transmural invasion of a bladder tumor in 4 of 15 patients. Prostatic involvement by urothelial carcinoma of the bladder was found in 37.1% of patients. Transurethral resection biopsy missed most tumors resulting from transmural invasion of the bladder primary lesion. Carcinoma in situ and invasive urothelial carcinoma arising from the prostatic urethra were detected in most cases. Transurethral resection biopsy of the prostatic urethra can complement staging and support clinical decision making with respect to neoadjuvant chemotherapy and planning for an orthotopic neobladder.

Incidental Prostate Cancer in Patients with Bladder Urothelial Carcinoma: Comprehensive Analysis of 1,476 Radical Cystoprostatectomy Specimens

We identified risk factors and determined the incidence and prognosis of incidental, clinically significant prostatic adenocarcinoma, prostatic urothelial carcinoma and HGPIN in patients treated with radical cystoprostatectomy for urothelial carcinoma of the bladder. We analyzed the records of 1,476 patients without a history of prostatic adenocarcinoma. We determined the incidence of clinically significant prostatic adenocarcinoma, prostatic urothelial carcinoma and HGPIN in the total cohort and in select patient subgroups. Prostatic urothelial carcinoma was stratified as prostatic stromal and prostatic urethral/duct involvement. Univariate and multivariate analyses were performed with multiple variables. Recurrence-free and overall survival rates were calculated. Median followup was 13.2 years. Of the 1,476 patients 753 (51.0%) had cancer involving the prostate. Prostatic adenocarcinoma, clinically significant prostatic adenocarcinoma, prostatic urothelial carcinoma and HGPIN were present in 37.9%, 8.3%, 21.1% and 51.2% of patients, respectively. Of the 312 patients (21.1%) with prostatic urothelial carcinoma 163 (11.0%) had prostatic urethral/duct involvement only and 149 (10.1%) had prostatic stromal involvement. We identified risk factors for clinically significant prostatic adenocarcinoma, prostatic urothelial carcinoma and HGPIN but the absence of these risk factors did not rule out their presence. Ten-year overall survival in patients with no prostatic urothelial carcinoma, and prostatic urethral/duct and prostatic stromal involvement was 47.1%, 43.3% and 21.7%, respectively (p<0.001). No patient with clinically significant prostatic adenocarcinoma died of prostatic cancer. More than half of the patients undergoing radical cystoprostatectomy had cancer involving the prostate. Prostatic urothelial carcinoma, particularly with prostatic stromal involvement, was associated with a worse prognosis, while clinically significant prostatic adenocarcinoma did not alter survival. Preoperative clinical and histopathological risk factors are not reliable enough to accurately predict clinically significant prostatic adenocarcinoma and/or prostatic urothelial carcinoma.

Editorial Comment to Characterization and risk stratification of prostate cancer in patients undergoing radical cystoprostatectomy

Radical cystoprostatectomy (RPE) with bilateral lymph node dissection and urinary diversion is the treatment of choice in muscle-invasive bladder cancer. Standard cystectomy includes en bloc prostatectomy providing the best oncological control, but is associated with substantial reduction of quality of life. The two main concerns regarding the functional results of this surgical method are affected continence and sexual function. Therefore, various modifications to standard cystectomy have been used to improve functional outcomes. All of these techniques aim to minimize dissection near the urinary sphincter and neurovascular bundles during cystectomy by partial or complete sparing of the prostate, seminal vesicles and vasa deferentia. These methods provided a remarkable improvement of functional results. 1 In contrast, leaving whole or part of the prostate behind raises concerns on oncological results.The two main risks of prostate-sparing cystectomy are overseeing a possible prostatic urothelial carcinoma and/or occult primary prostate cancer (PCA) in these patients. The rationale for this is that both urothelial carcinoma and PCA were reported to be frequent incidental findings in RPE specimens. In the absence of randomized clinical trials, the direct comparison of oncological risks between RPE and prostate-sparing cystectomy is not possible. Therefore, critical analysis of single risk factors and their combinations described in different retrospective studies remains the only way to draw conclusions regarding the risks of various cystectomy methods. This present study 2 is the largest to date assessing the prevalence and risk of occult PCA in patients treated with RPE. Buse et al. found PCA in 18% of RPE specimens, which is at the lower end of the PCA prevalence published so far. The rate of high-risk PCA was <2% over the whole patient cohort, and is ~10% of all detected PCAs, showing that most identified PCA in RPE specimens are clinically indolent. Formerly, Thomas et al. showed that preoperatively available predictors, such as serum prostate-specific antigen level and digital rectal examination are able to sensitively identify clinically significant PCA before radical surgery. 3 However, others drew different conclusions. 4 Therefore, as oncological results have to overweigh functional outcomes, careful selection for prostate-sparing surgery remains important. Using strict selection criteria for prostate-sparing cystectomy, de Vries et al. were able to reach comparable oncological results to that of standard RPE. 5 However, such strict inclusion criteria substantially reduce the availability of this technique. More accurate risk stratification is therefore required to increase availability with maintained oncological efficacy. A further interesting finding of the study by Buse et al. 2 was the independent and unfavorable prognostic value of the presence of PCA in RPE specimens. Unfortunately, data on cause of death were not available; therefore, the authors were not able to conclude whether the additional risk by PCA is a result of the PCA-related deaths. However, the low prevalence of high-risk PCA found in the present study suggests that the additional risk by the presence of PCA is independent from PCA-related deaths. Based on this, it can be presumed that concomitant PCA supports bladder cancer progression. However, more convincing clinical and molecular evidence is required to confirm this hypothesis.

Abstract 5258: Characterization of canine lower urinary tract carcinoma cell lines with variable DNA mismatch repair proficiency derived from a single tumor

Abstract Deficiencies in the DNA mismatch repair system (MMR) have been well described in a variety of neoplasms in humans; however, naturally occurring animal models of MMR deficiency associated carcinogenesis are lacking. Recently, our lab has shown that deficiencies in the MMR are common in canine lower urinary tract carcinomas through the identification of microsatellite instability and decreased expression of MSH2. In order to further investigate MMR in the dog, cell lines were derived from canine lower urinary tract carcinomas. Briefly, samples of a prostatic urothelial carcinoma from an 8-year-old neutered male Beagle were minced into 0.5-1mm3 pieces and incubated in culture plates with 1:1 DMEM/F12 supplemented with 10% fetal bovine serum, penicillin, streptomycin, and l-glutamine. Resulting colonies of epithelioid cells were harvested with 0.05% trypsin and subcultured. Two distinct cell populations emerged following repeated subculture, which were subsequently isolated from one another through selective trypinization. Thus, two distinct cell lines, TYLER1 and TYLER2, were established. While these cell lines were derived from the same tumor, they differ greatly in terms of morphology and expression of DNA mismatch repair genes. Cells of TYLER1 are polygonal with regular dimensions, and grow in fairly discrete aggregates. Cells of TYLER2 are spindle-shaped to stellate, and grow in haphazardly arranged interlacing patterns. Both cell lines express cytokeratins confirming their epithelial origin; however, the specific cytokeratins expressed by each line differs and both cell lines strongly express vimentin. In contrast to the primary tumor, both cell lines express prostatic acid phosphatase (PAP), a marker of prostatic differentiation, and neither cell line expresses uroplakin III, an urothelial marker. This is likely a reflection of plasticity of cells of the lower urinary tract in terms of their ability to differentiate. Comparing microsatellite sequences obtained from a blood sample from the dog of origin to those in the cell lines, there is variability in the length of select microsatellites suggesting functional MMR deficiency. The gene and protein expression of MSH2 and MSH6 are significantly lower in TYLER2 than TYLER1 as determined by Western blot and RT PCR, respectively. In preliminary studies using XTT assays, the MMR deficient TYLER2 cell line is more sensitive to gemcitabine and carboplatin than TYLER1, although both are more sensitive to these agents than other canine urothelial carcinoma cell lines that strongly express MSH2 and MSH6. Overall, given the differences in apparent MMR expression and differences observed in morphology and response to treatment, these cell lines will undoubtedly prove valuable in future studies of MMR in dogs and the effects MMR deficiency on cancer treatment response and progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5258. doi:1538-7445.AM2012-5258

Primary transitional cell carcinoma of the prostate: a male disease with dismal prognosis despite cisplatin-based systemic chemotherapy

Background Primary urothelial carcinoma of the prostate is an infrequent male malignancy with a dismal prognosis, that originates in the periurethral prostatic gland. This neoplasia is considered, in general terms, to be chemosensitive but prospective trials regarding therapy and prognosis are lacking, due to the infrequent nature of this entity. This paper is a case series regarding the accumulated experience in our institution with the use of cisplatin-based chemotherapeutic regimens in these patients. Methods The clinico-pathological findings of a series of 12 patients with primary urothelial carcinoma of the prostate diagnosed and treated over a 10 year period are reviewed, with an emphasis on therapy and evolution. Results No patient in the series reached long-term survival. Mean time to death was 24.1 months (range 5–48 months). The combination of local treatment plus cisplatin-based systemic chemotherapy did not achieve satisfactory results. However, patients treated with radical surgery (cystectomy or prostatectomy) and at least 3 cycles of multiple chemotherapy behaved better than the rest. Radical surgery achieved better local control than radiotherapy, but repeated transurethral resection of the prostate plus systemic chemotherapy may also provide local control in selected patients. Conclusion Despite combined therapeutic efforts that pursued both local control and the prevention of a systemic relapse, the prognosis of advanced primary prostatic urothelial carcinoma remains dismal. Early diagnosis appears difficult because clinical presentation differs to that of males with adenocarcinoma of the prostate or invasive transitional cell carcinoma (TCC) of the bladder. Cisplatin-based systemic chemotherapy does not allow prolonged survival.

Outcomes of patients undergoing radical cystoprostatectomy for bladder cancer with prostatic involvement on final pathology

To evaluate the impact of prostatic urothelial carcinoma (PUC) on survival of patients with bladder cancer undergoing radical cystoprostatectomy (RCP). From 1998 to 2005, 463 consecutive RCPs were performed for UC of the bladder. Patients with PUC at final pathology were grouped by route of prostatic invasion (bladder origin or prostatic urethral origin) and by depth of invasion (carcinoma in situ, ductal invasion, and stromal invasion). Univariate and multivariate survival analyses were performed. In all, 35% (162/463) of patients had PUC. The 3-year overall survival (OS) was 58.2% for patients who did not have PUC, 59.2%, 51.7%, and 16.8% in order of increasing depth of prostatic invasion for patients with PUC of urethral origin, and 6.7% for patients with bladder-origin PUC. Survival differed significantly between stromal and non-stromal PUC (P < 0.001). Patients with PUC of bladder origin had a higher rate of positive lymph nodes (LNs) than patients with stromal PUC of prostate origin (74.3% vs 27.8%, P < 0.001), but survival was similar (P = 0.619). On multivariate analysis, age (P = 0.035), increasing bladder stage (P = 0.003), stromal invasion (P = 0.002) and positive LNs (P < 0.001) were predictors of poor OS. Depth of prostatic invasion correlates with outcome. While prostatic involvement originating in the bladder is associated with higher rates of positive LNs, survival is similar to patients with stromal involvement of urethral origin. Age, bladder tumour stage, prostatic stromal involvement and positive LNs predict adverse outcome. Our data support separate staging of the prostate in RCP specimens.

Prostatic urothelial carcinoma: is transurethral prostatectomy necessary before bacillus Calmette‐Guérin immunotherapy?

To evaluate the efficacy of transurethral prostatectomy (TURP) followed by bacillus Calmette-Guérin (BCG) immunotherapy in patients with prostatic urothelial carcinoma (PUC) and compare the results of studies using combined TURP and BCG with studies in which TURP was not performed. Patients with bladder cancer and PUC were treated with TURP followed by six weekly intravesical instillations of BCG. Response was determined and monitored by periodic bladder and prostatic urethra biopsies and urinary cytology. Also, the outcome of previous series using similar methodology was compared with the outcome of studies in which TURP was not performed. In all, 20 patients with PUC were treated with TURP followed by intravesical instillations of BCG. The median follow-up was 52.5 months. All patients had an initial complete response (CR). The prostatic urethra 5-year recurrence-free survival rate was 90%. However, bladder and prostatic urethra 5-year recurrence-free survival rate was only 30%. Five patients (25%) died from urothelial carcinoma (UC) after a median period of 58.5 months (two from bladder cancer metastases and three from upper tract metastases). The long-term prostatic urethra CR rate in studies using TURP before immunotherapy was significantly higher than the CR rate in studies using immunotherapy alone (P < 0.001). However, there was no difference when bladder and prostatic urethra CR rates were considered together (P = 0.54). In patients with PUC, TURP before BCG immunotherapy eliminates PUC in most cases, and is probably the preferred treatment for this disease. The risk of UC-specific mortality in these patients is high.

Pathology of the prostate in radical cystectomy specimens: A critical review

Our aim was to critically review clinico-pathological features of incidental prostate tumors in cystoprostatectomy specimens and to evaluate implications for patients' management. Data were identified by a structured MEDLINE search. Studies addressing incidence, pathological characteristics, and/or clinical significance of prostate tumors or related pre-malignant lesions from cystoprostatectomy series were reviewed in detail. The reported incidence of prostate adenocarcinoma in cystectomy specimens is highly variable and mostly depending on the histopathology technique of sampling. The clinical significance of these incidentally discovered cancers remains questionable, as the outcome of patients depends on the prognosis of the bladder tumor. For those candidates for prostate sparing surgery, it seems reasonable to include a routine prostate biopsy in the standard preoperative work-up as relevant PSA values to exclude cancer are lacking. Reports of prostatic urethral involvement at the time of radical cystectomy are mostly retrospective. Thus, it is likely that the true incidence of involvement with urothelial carcinoma is underreported. It has been suggested that multifocal bladder tumors, CIS in the bladder and bladder tumor location in the bladder neck are independent risk factors for prostatic urothelial carcinoma. Prostatic stromal involvement, which reflects the depth of invasion, is the most important prognostic factor. Poorly differentiated prostate adenocarcinoma and urothelial carcinoma often share overlapping morphologic features and it can be sometimes difficult to differentiate between these two entities.

Dilemmas in the treatment of urothelial cancers of the prostate

The objective of this paper is to examine the contemporary incidence, diagnosis, and treatment of prostatic urothelial carcinoma and make recommendations on the current dilemmas of treating urothelial cancer of the prostate. A review of English-language literature from 1990 to the present was performed utilizing the U.S. National Library of Medicine's Pub Med database. Keywords used were urothelial cell carcinoma, prostatic urethral involvement, prostatic duct/acini involvement, carcinoma in situ. Bibliographies of reviewed articles were also searched. Transitional cell carcinoma of the bladder with involvement of the prostate has been reported in multiple studies with an incidence between 12% and 48%. Stromal invasion of the prostate has a reported incidence between 7% and 17%. The incidence of primary transitional cell carcinoma of the prostate has been estimated at 1% to 4% of prostatic malignancies. Degree and depth of prostatic invasion has prognostic significance with 5-year survival rates being 100% for those with urethral mucosal involvement, 50% with ductal/acinar involvement, and 40% with prostatic stromal invasion. The actual anatomic path that urothelial carcinoma invasion occurs also has prognostic significance. Those with contiguous malignant involvement had a 7% 5-year survival rate compared with those with noncontiguous involvement and a 46% 5-year survival rate. Prostatic urothelial carcinoma is often under appreciated and not well understood. Malignant involvement of different anatomic locations of the prostate (i.e., mucosa, ducts, acini, and stroma) influence not only diagnosis but treatment of disease. Although debate exists regarding optimal therapy for mucosal involvement, if the prostatic stroma is involved, radical cystoprostatectomy is the treatment of choice.