The Impact of Histologic Subtypes on Clinical Outcomes After Radiation-Based Therapy for Muscle-Invasive Bladder Cancer.

PURPOSE: Outcomes of radiation-based therapy (RT) for muscle-invasive bladder cancer (MIBC) with histologic subtypes of urothelial cancer (HS-UC) are lacking. Our objective was to compare survival outcomes of pure urothelial carcinoma (PUC) to HS-UC after RT. MATERIALS AND METHODS: A multicenter retrospective study of 864 patients with MIBC who underwent curative-intent RT to the bladder for MIBC (clinical T2-T4aN0-2M0) between 2001 and 2018 was conducted. Regression models were used to test the association between HS-UC and complete response (CR) and survival outcomes after RT. RESULTS: In total, 122 patients (14%) had HS-UC. Seventy-five (61%) had HS-UC with squamous and/or glandular differentiation. A CR was confirmed in 69% of patients with PUC and 63% with HS-UC. There were 207 (28%) and 31 (25%) patients who died of metastatic bladder cancer in the PUC and HS-UC groups, respectively. There were 361 (49%) and 58 (48%) patients who died of any cause in the PUC and HS-UC groups, respectively. Survival outcomes were not statistically different between the groups. The HS-UC status was not associated with survival outcomes in multivariable Cox regression analyses. CONCLUSIONS: In our study, HS-UC responded to RT with no significant difference in CR and survival outcomes compared to PUC. The presence of HS-UC in MIBC does not seem to confer resistance to RT, and patients should not be withheld from bladder preservation therapy options. Due to low numbers, definitive conclusions cannot be drawn for particular histologic subtypes.

Ileal conduit: standard urinary diversion for elderly patients undergoing radical cystectomy.

PURPOSE: Ileal conduit (IC) is the most frequent urinary diversion (UD) performed after radical cystectomy (RC). We reviewed the literature to investigate the factors influencing the choice of this diversion and its complications. METHODS: A literature search (PubMed) was performed for all English language publications on UDs performed for treatment of bladder cancer from 1950 to 2015. The literature review was focused on studies reporting outcome of IC and its comparison with other types of UDs. RESULTS: IC is the most common UD performed in elderly patients undergoing RC for bladder cancer. Long-term studies looking at the change in renal function after UD report a universal decline in the glomerular filtration rate; however, this decline in renal function is the least for IC. There is a significant morbidity of RC (20-56 %), which can be attributed to patient factors, surgical technique and hospital volume. Modern concepts of bowel preparation, postoperative nutrition, early enteral feeding and involvement of stoma therapists have helped improve the outcomes. The quality of life is preserved, and in many including elderly, it may be improved with IC UD. CONCLUSIONS: IC is the most commonly performed UD following radical cystectomy. It is associated with acceptable morbidity and has the lowest reoperation rates as compared to continent diversion. It is also the procedure of choice for most patients' elderly patients as well as patients with limited dexterity, poor motivation, anatomical restrictions and poor renal function. Studies measuring HRQOL report excellent patient acceptability, especially in the elderly population.

The role of adjuvant chemotherapy for lymph node-positive upper tract urothelial carcinoma following radical nephroureterectomy: a retrospective study.

OBJECTIVE: To evaluate the effect of adjuvant chemotherapy (AC) on mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) with positive lymph nodes (LNs) and to identify patient subgroups that are most likely to benefit from AC. PATIENTS AND METHODS: We retrospectively analysed data of 263 patients with LN-positive UTUC, who underwent full surgical resection. In all, 107 patients (41%) received three to six cycles of AC, while 156 (59.3%) were treated with RNU alone. UTUC-related mortality was evaluated using competing-risks regression models. RESULTS: In all patients (T(all) N+), administration of AC had no significant impact on UTUC-related mortality on univariable (P = 0.49) and multivariable (P = 0.11) analysis. Further stratified analyses showed that only N+ patients with pT3-4 disease benefited from AC. In this subgroup, AC reduced UTUC-related mortality by 34% (P = 0.019). The absolute difference in mortality was 10% after the first year and increased to 23% after 5 years. On multivariable analysis, administration of AC was associated with significantly reduced UTUC-related mortality (subhazard ratio 0.67, P = 0.022). Limitations of this study are the retrospective non-randomised design, selection bias, absence of a central pathological review and different AC protocols. CONCLUSIONS: AC seems to reduce mortality in patients with pT3-4 LN-positive UTUC after RNU. This subgroup of LN-positive patients could serve as target population for an AC prospective randomised trial.

Evaluation of MRI-TRUS fusion versus cognitive registration accuracy for MRI-targeted, TRUS-guided prostate biopsy.

OBJECTIVE: The purpose of this article is to compare transrectal ultrasound (TRUS) biopsy accuracies of operators with different levels of prostate MRI experience using cognitive registration versus MRI-TRUS fusion to assess the preferred method of TRUS prostate biopsy for MRI-identified lesions. SUBJECTS AND METHODS; One hundred patients from a prospective prostate MRI-TRUS fusion biopsy study were reviewed to identify all patients with clinically significant prostate adenocarcinoma (PCA) detected on MRI-targeted biopsy. Twenty-five PCA tumors were incorporated into a validated TRUS prostate biopsy simulator. Three prostate biopsy experts, each with different levels of experience in prostate MRI and MRI-TRUS fusion biopsy, performed a total of 225 simulated targeted biopsies on the MRI lesions as well as regional biopsy targets. Simulated biopsies performed using cognitive registration with 2D TRUS and 3D TRUS were compared with biopsies performed under MRI-TRUS fusion. RESULTS: Two-dimensional and 3D TRUS sampled only 48% and 45% of clinically significant PCA MRI lesions, respectively, compared with 100% with MRI-TRUS fusion. Lesion sampling accuracy did not statistically significantly vary according to operator experience or tumor volume. MRI-TRUS fusion-naïve operators showed consistent errors in targeting of the apex, midgland, and anterior targets, suggesting that there is biased error in cognitive registration. The MRI-TRUS fusion expert correctly targeted the prostate apex; however, his midgland and anterior mistargeting was similar to that of the less-experienced operators. CONCLUSION: MRI-targeted TRUS-guided prostate biopsy using cognitive registration appears to be inferior to MRI-TRUS fusion, with fewer than 50% of clinically significant PCA lesions successfully sampled. No statistically significant difference in biopsy accuracy was seen according to operator experience with prostate MRI or MRI-TRUS fusion.

Obesity is associated with worse oncological outcomes in patients treated with radical cystectomy.

OBJECTIVE: To investigate the association between body mass index (BMI) and oncological outcomes in patients after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) in a large multi-institutional series. PATIENTS AND METHODS: Data were collected from 4118 patients treated with RC and pelvic lymphadenectomy for UCB. Patients receiving preoperative chemotherapy or radiotherapy were excluded. Univariable and multivariable models tested the effect of BMI on disease recurrence, cancer-specific mortality and overall mortality. BMI was analysed as a continuous and categorical variable (<25 vs 25-29 vs ≥30 kg/m(2)). RESULTS: Median BMI was 28.8 kg/m(2) (interquartile range 7.9); 25.3% had a BMI <25 kg/m(2), 32.5% had a BMI between 25 and 29.9 kg/m(2), and 42.2% had a BMI ≥30 kg/m(2). Patients with a higher BMI were older (P < 0.001), had higher tumour grade (P < 0.001), and were more likely to have positive soft tissue surgical margins (P = 0.006) compared with patients with lower BMI. In multivariable analyses that adjusted for the effects of standard clinicopathological features, BMI >30 was associated with higher risk of disease recurrence (hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.46-1.91, P < 0.001), cancer-specific mortality (HR 1.43, 95% CI 1.24-1.66, P < 0.001), and overall mortality (HR 1.81, CI 1.60-2.05, P < 0.001). Themain limitation is the retrospective design of the study. CONCLUSIONS: Obesity is associated with worse cancer-specific outcomes in patients treated with RC for UCB. Focusing on patient-modifiable factors such as BMI may have significant individual and public health implications in patients with invasive UCB.

Perineural invasion and TRUS findings are complementary in predicting prostate cancer biology.

INTRODUCTION: Clinical variables with more accuracy to predict biologically insignificant prostate cancer are needed. We evaluated the combination of transrectal ultrasound-guided biopsy of the prostate (TRUSBx) pathologic and radiologic findings in their ability to predict the biologic potential of each prostate cancer. MATERIALS AND METHODS: A total of 1043 consecutive patients who underwent TRUSBx were reviewed. Using pathologic criteria, patients with prostate cancer (n = 529) and those treated with radical prostatectomy (RP) (n = 147) were grouped as: "insignificant" (Gleason score ≤ 6, prostate-specific antigen (PSA) density ≤ 0.15 ng/ml, tumor in ≤ 50% of any single core, and < 33% positive cores) and "significant" prostate cancer. TRUSBx imaging and pathology results were compared with the RP specimen to identify factors predictive of "insignificant" prostate cancer. RESULTS: TRUSBx pathology results demonstrated perineural invasion in 36.4% of "significant" versus 5.4% of "insignificant" prostate cancers (p < 0.01) and pathologic invasion of periprostatic tissue in 7% of significant versus 0% of insignificant prostate cancers (p < 0.01). TRUS findings concerning for neoplasia were associated with significant tumors (p < 0.01). Multivariable analysis demonstrated perineural invasion in the biopsy specimen (p = 0.03), PSA density (p = 0.02) and maximum tumor volume of any core (p = 0.02) were independently predictive of a significant prostate cancer. CONCLUSIONS: TRUS findings concerning for measurable tumor and perineural invasion in TRUSBx specimens appear to be complementary to Epstein's pathologic criteria and should be considered to aid in the determination whether a prostate cancer is organ-confined and more likely to be biologically insignificant.

Radiation-based Therapy for Muscle-invasive Bladder Cancer: Contemporary Outcomes Across Tertiary Centers.

BACKGROUND: Radiation therapy (RT) is an alternative to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). OBJECTIVE: To analyze predictors of complete response (CR) and survival after RT for MIBC. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter retrospective study of 864 patients with nonmetastatic MIBC who underwent curative-intent RT from 2002 to 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Regression models were used to explore prognostic factors associated with CR, cancer-specific survival (CSS), and overall survival (OS). RESULTS AND LIMITATIONS: The median patient age was 77 yr and median follow-up was 34 mo. Disease stage was cT2 in 675 patients (78%) and cN0 in 766 (89%). Neoadjuvant chemotherapy (NAC) was given to 147 patients (17%) and concurrent chemotherapy to 542 (63%). A CR was experienced by 592 patients (78%). cT3-4 stage (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.29-0.63; p < 0.001) and hydronephrosis (OR 0.50, 95% CI 034-0.74; p = 0.001) were significantly associated with lower CR. The 5-yr survival rates were 63% for CSS and 49% for OS. Higher cT stage (HR 1.93, 95% CI 1.46-2.56; p < 0.001), carcinoma in situ (HR 2.10, 95% CI 1.25-3.53; p = 0.005), hydronephrosis (HR 2.36, 95% CI 1.79-3.10; p < 0.001), NAC use (HR 0.66, 95% CI 0.46-0.95; p = 0.025), and whole-pelvis RT (HR 0.66, 95% CI 0.51-0.86; p = 0.002) were independently associated with CSS; advanced age (HR 1.03, 95% CI 1.01-1.05; p = 0.001), worse performance status (HR 1.73, 95% CI 1.34-2.22; p < 0.001), hydronephrosis (HR 1.50, 95% CI 1.17-1.91; p = 0.001), NAC use (HR 0.69, 95% CI 0.49-0.97; p = 0.033), whole-pelvis RT (HR 0.64, 95% CI 0.51-0.80; p < 0.001), and being surgically unfit (HR 1.42, 95% CI 1.12-1.80; p = 0.004) were associated with OS. The study is limited by the heterogeneity of different treatment protocols. CONCLUSIONS: RT for MIBC yields a CR in most patients who elect for curative-intent bladder preservation. The benefit of NAC and whole-pelvis RT require prospective trial validation. PATIENT SUMMARY: We investigated outcomes for patients with muscle-invasive bladder cancer treated with curative-intent radiation therapy as an alternative to surgical removal of the bladder. The benefit of chemotherapy before radiotherapy and whole-pelvis radiation (bladder plus the pelvis lymph nodes) needs further study.

Ghrelin receptor as a novel imaging target for prostatic neoplasms.

BACKGROUND: Ghrelin is a natural growth hormone secretagogue (GHS) that is co-expressed with its receptor GHSR in human prostate cancer (PCa) cells. Imaging probes that target receptors for ghrelin may delineate PCas from benign disease. The specificity of a novel ghrelin-imaging probe for PCa over normal tissue or benign disease was assessed. METHODS: A fluorescein-bearing ghrelin analogue was synthesized (fluorescein-ghrelin(1-18)), and its application for imaging was evaluated in a panel of PCa cell lines and human prostate tissue. Prostate core biopsy samples were collected from fresh surgery specimens of 13 patients undergoing radical prostatectomy. Ghrelin probe signal was detected and quantified in each sample using a hapten amplification technique and associated with pathological features. RESULTS: The ghrelin probe was taken up by GHSR-expressing LNCaP and PC-3 cells, and not in BPH cells that express low levels of GHSR. Binding was blocked by competition with excess unlabeled probe. The ghrelin probe signal was 4.7 times higher in PCa compared to benign hyperplasia tissue (P = 0.0027) and normal tissue (P = 0.0093). Furthermore, while the ghrelin probe signal was 1.9-fold higher in PIN compared to benign hyperplasia (P = 0.0022) and normal tissue (P = 0.0047), there was no significant difference in the signal of benign hyperplasia compared to normal tissue. CONCLUSION: The imaging probe fluorescein-ghrelin(1-18) is specific for PCa, and did not associate significantly with benign hyperplasia or normal prostate tissue. This data suggests that ghrelin analogues may be useful as molecular imaging probes for prostatic neoplasms in both localized and metastatic disease.

Prognostic risk stratification of pathological stage T3N0 bladder cancer after radical cystectomy.

PURPOSE: Patients with pathological T3N0 stage urothelial carcinoma of the bladder show a range of outcomes after radical cystectomy. Given that nomograms have included heterogeneous groups of patients, we focused on and stratified patients with pT3N0 urothelial carcinoma of the bladder after radical cystectomy into prognostically different risk groups to facilitate the development of adjuvant therapy trials for those at high risk. MATERIALS AND METHODS: The study comprised a total of 578 patients from 9 centers worldwide with pT3N0 urothelial carcinoma of the bladder who underwent radical cystectomy without perioperative chemotherapy. We evaluated the effect of pT3 substage at radical cystectomy, age, grade, lymphovascular invasion, margin status and number of lymph nodes removed on recurrence-free survival using Cox regression analysis. A weighted prognostic model was devised. RESULTS: Median followup was 39.4 months (IQR 64). On multivariate analysis pT3 substage at radical cystectomy (pT3b vs pT3a HR 2.056, p <0.0001), lymphovascular invasion (positive vs negative HR 2.004, p <0.0001) and margin status (positive vs negative HR 2.503, p = 0.002) were associated with recurrence-free survival (concordance index 0.66) in the context of generally adequate lymph node dissection, that is with a median of 17 removed. Three risk groups were devised based on weighted variables with a 5-year recurrence-free survival rate of 79% (95% CI 70-84), 57% (95% CI 50-64) and 37% (95% CI 26-48) in the low, intermediate and high risk groups, respectively. CONCLUSIONS: We constructed a user friendly prognostic risk model for patients with pT3N0 urothelial carcinoma of the bladder treated with radical cystectomy based on pT3 substage at radical cystectomy, lymphovascular invasion and margin status. These data warrant validation and may enable tailored monitoring and selection of appropriate patients for adjuvant therapy trials.

Disease-free survival at 2 or 3 years correlates with 5-year overall survival of patients undergoing radical cystectomy for muscle invasive bladder cancer.

PURPOSE: The conventional primary end point in trials of perioperative systemic therapy for muscle invasive bladder cancer is 5-year overall survival. We identified an association between disease-free survival at 2 to 3 years and 5-year overall survival. MATERIALS AND METHODS: We retrospectively analyzed a multicenter database containing records of 2,724 patients treated with radical cystectomy for muscle invasive bladder cancer with negative margins. Of these patients 844 had received adjuvant chemotherapy. We evaluated the association of disease-free survival at 2 and 3 years with overall survival at 5 years using Cox proportional hazards modeling and the kappa statistic. RESULTS: Overall 2-year/3-year disease-free survival was 0.63/0.57 and 5-year overall survival was 0.47. The overall agreement between 2-year disease-free survival and 5-year overall survival was 79%, and between 3-year disease-free survival and 5-year overall survival was 81%. Agreements were similar when analyzed within pathological substages, radical cystectomy decades and adjuvant chemotherapy subgroups. The kappa statistic was 0.57 (95% CI 0.53-0.60) for 2-year disease-free survival/5-year overall survival and 0.61 (95% CI 0.58-0.64) for 3-year disease-free survival/5-year overall survival, indicating moderate agreement. The hazard ratio for disease-free survival as a time dependent variable was 12.7 (95% CI 11.60-13.90), indicating a strong relationship between disease-free and overall survival. CONCLUSIONS: Disease-free survival rates at 2 and 3 years correlate with and are potential intermediate surrogates for 5-year overall survival in patients treated with radical cystectomy for muscle invasive bladder cancer regardless of adjuvant chemotherapy. These data warrant external validation and may expedite the development of adjuvant systemic therapy. In addition, they may be applicable to the neoadjuvant setting.

Cumulative summation graphs are a useful tool for monitoring positive surgical margin rates in robot-assisted radical prostatectomy.

OBJECTIVE: • To explore the usefulness of cumulative summation (CUSUM) graphs for monitoring positive surgical margin (PSM) rates during a surgeon's transition from open to robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: • Data were prospectively collected from patients undergoing RARP by a single surgeon. • Preoperatively all patients were either low or moderate risk under the D'Amico classification system. • A CUSUM graph was charted retrospectively to analyse the PSM rate in patients undergoing RARP for pathological stage T2 (pT2) disease. • Acceptable and unacceptable PSM rates were set at 10% and 15% respectively. RESULTS: • From a cohort of 226 patients, 158 patients with pT2 disease were selected. The mean (range) age of these patients was 59.2 (39-73) years, the median (range) Gleason score was 6 (4-9), the mean (range) PSA was 6.43 (0.52-17.5) ng/mL and the mean (range) prostate volume was 44 (18-120) cm(3). In all, 21 patients had PSMs (13%). • CUSUM graphs were produced and clearly demonstrated the change in PSM rate over time. CONCLUSION: • CUSUM graphs are a novel and useful visual representation of the learning curve for surgeons. • PSM rates in patients with pT2 disease are a good outcome to monitor using CUSUM graphs as they are binary and lack the confounding factors associated with other outcomes such as continence and erectile dysfunction. • We advocate the use of CUSUM graphs as a method of quality assurance with the introduction of a robotics programme.

Discrepancy between clinical and pathological stage: external validation of the impact on prognosis in an international radical cystectomy cohort.

OBJECTIVE: • To compare the clinical and pathologic stage among a large, multi-institutional series of patients undergoing radical and to determine the effect of stage discrepancy on outcomes. PATIENTS AND METHODS: • Data was collected from nine centers and 3,393 patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy and pelvic lymphadenectomy without neo-adjuvant chemotherapy. • A retrospective cohort design was used to assess the percentage of patients experiencing stage discrepancy and the impact of stage discrepancy on time to disease relapse and time to death from UCB. RESULTS: • Clinical under staging occurred in 50% of patients and pathologic down staging occurred in 18% of patients. • Up staging to muscle invasive disease occurred in 45.9% (n = 592) of 1,291 patients with clinical ≤T1, including 30.6% of patients with Tis only at transurethral resection. • Of the 3,166 patients with clinically organ confined (OC) tumor stage, 1,357 (42.9%) were up staged to non-organ confined pathologic tumor stage. • Within each clinical stage stratum, patients who were clinically under staged had a higher probability of disease relapse or death from UCB compared to those who were same staged or down staged on pathologic examination (P < 0.05). CONCLUSIONS: • We identified clinical under staging in half of the patients undergoing radical cystectomy for UCB. • Up staging resulted in a higher likelihood of disease progression and eventual death from UCB. • These findings should be considered when utilizing pre-operative risk-adapted strategies for selecting candidates for neoadjuvant chemotherapy.

Prognostic risk stratification of pathological stage T2N0 bladder cancer after radical cystectomy.

OBJECTIVE: • To stratify risk of pathological (p) T2N0 urothelial carcinoma of the bladder after radical cystectomy (RC) based on pathological factors to facilitate the development of adjuvant therapy trials for high-risk patients. PATIENTS AND METHODS: • The study comprised 707 patients from a database of patients with pT2N0 urothelial carcinoma of the bladder who had undergone RC and not received perioperative chemotherapy. • The effect of residual pT-stage at RC, age, grade, lymphovascular invasion and number of lymph nodes removed on recurrence-free survival was evaluated using Cox regression analyses. A weighted prognostic model was devised with significant variables. RESULTS: • The median follow up was 60.9 months. In multivariable analyses, residual disease at RC (pT2a: hazard ratio (HR) 1.740, P = 0.03; for pT2b: HR 3.075, P < 0.001; both compared with

Concomitant carcinoma in situ in cystectomy specimens is not associated with clinical outcomes after surgery.

OBJECTIVE: The aim of this study was to externally validate the prognostic value of concomitant urothelial carcinoma in situ (CIS) in radical cystectomy (RC) specimens using a large international cohort of bladder cancer patients. METHODS: The records of 3,973 patients treated with RC and bilateral lymphadenectomy for urothelial carcinoma of the bladder (UCB) at nine centers worldwide were reviewed. Surgical specimens were evaluated by a genitourinary pathologist at each center. Uni- and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality after RC. RESULTS: 1,741 (43.8%) patients had concomitant CIS in their RC specimens. Concomitant CIS was more common in organ-confined UCB and was associated with lymphovascular invasion (p < 0.001). Concomitant CIS was not associated with either disease recurrence or cancer-specific death regardless of pathologic stage. The presence of concomitant CIS did not improve the predictive accuracy of standard predictors for either disease recurrence or cancer-specific death in any of the subgroups. CONCLUSIONS: We could not confirm the prognostic value of concomitant CIS in RC specimens. This, together with the discrepancy between pathologists in determining the presence of concomitant CIS at the morphologic level, limits the clinical utility of concomitant CIS in RC specimens for clinical decision-making.

Total pelvic exenteration for rectal cancer: outcomes and prognostic factors.

BACKGROUND: To perform complete resection of locally advanced and recurrent rectal carcinoma, total pelvic exenteration (TPE) may be attempted. We identified disease-related outcomes and prognostic factors. METHODS: We conducted a single-centre review of patients who underwent TPE for rectal carcinoma over a 10-year period. RESULTS: We included 28 patients in our study. After a median follow-up of 35 months, 53.6% of patients were alive with no evidence of disease. The 3-year actuarial disease-free and overall survival rates were 52.2% and 75.1%, respectively. On univariate analysis, recurrent disease, preoperative body mass index greater than 30 and lymphatic invasion were poor prognostic factors for disease-free survival, and only lymphatic invasion predicted overall survival. Additionally, multivariate analysis identified lymphatic invasion as an independent poor prognostic factor for disease-free survival in this patient population with locally advanced and recurrent rectal carcinoma. CONCLUSION: Despite the significant morbidity, TPE can provide long-term survival in patients with rectal carcinoma. Additionally, lymphatic invasion on final pathology was an independent prognostic factor for disease-free survival.

Repeat prostate biopsy accuracy: simulator-based comparison of two- and three-dimensional transrectal US modalities.

PURPOSE: To compare the accuracy of biopsy with two-dimensional (2D) transrectal ultrasonography (US) with that of biopsy with conventional three-dimensional (3D) transrectal US and biopsy with guided 3D transrectal US in the guidance of repeat prostate biopsy procedures in a prostate biopsy simulator. MATERIALS AND METHODS: The institutional review board approved this retrospective study. Five residents and five experts performed repeat biopsies with a biopsy simulator that contained the transrectal US prostate images of 10 patients who had undergone biopsy. Simulated repeat biopsies were performed with 2D transrectal US, conventional 3D transrectal US, and guided 3D transrectal US (an extension of 3D transrectal US that enables active display of biopsy targets). The modalities were compared on the basis of time per biopsy and how accurately simulated repeat biopsies could be guided to specific targets. The probability for successful biopsy of a repeat target was calculated for each modality. RESULTS: Guided 3D transrectal US was significantly (P < .01) more accurate for simulated biopsy of repeat targets than was 2D or 3D transrectal US, with a biopsy accuracy of 0.86 mm +/- 0.47 (standard deviation), 3.68 mm +/- 2.60, and 3.60 mm +/- 2.57, respectively. Experts had a 70% probability of sampling a prior biopsy target volume of 0.5 cm(3) with 2D transrectal US; however, the probability approached 100% with guided 3D transrectal US. Biopsy accuracy was not significantly different between experts and residents for any modality; however, experts were significantly (P < .05) faster than residents with each modality. CONCLUSION: Repeat biopsy of the prostate with 2D transrectal US has limited accuracy. Compared with 2D transrectal US, the biopsy accuracy of both experts and residents improved with guided 3D transrectal US but did not improve with conventional 3D transrectal US.

Soft tissue surgical margin status is a powerful predictor of outcomes after radical cystectomy: a multicenter study of more than 4,400 patients.

PURPOSE: We evaluated the association of soft tissue surgical margins with characteristics and outcomes of patients treated with radical cystectomy for urothelial carcinoma of the bladder. MATERIALS AND METHODS: We retrospectively collected the data of 4,410 patients treated with radical cystectomy and pelvic lymphadenectomy without neoadjuvant chemotherapy at 12 academic centers in the United States, Canada and Europe. A positive soft tissue surgical margin was defined as presence of tumor at inked areas of soft tissue on the radical cystectomy specimen. RESULTS: Positive soft tissue surgical margins were identified in 278 patients (6.3%). On univariate analysis positive soft tissue surgical margin was significantly associated with advanced pT stage, higher tumor grade, lymphovascular invasion and lymph node metastasis (p <0.001). Actuarial 5-year recurrence-free and cancer specific survival probabilities were 62.8% +/- 0.8% and 69% +/- 0.8% for patients without soft tissue surgical margins vs 21.6% +/- 3.1% and 26.4% +/- 3.3% for those with positive soft tissue surgical margins (p <0.001). On multivariable analyses adjusting for the effect of standard clinicopathological features and adjuvant chemotherapy positive soft tissue surgical margin was an independent predictor of disease recurrence and cancer specific mortality (HR 1.52 and HR 1.51, p <0.001, respectively). Soft tissue surgical margin retained independent predictive value in subgroups with advanced disease such as pT3Nany, pT4Nany or Npositive. CONCLUSIONS: Positive soft tissue surgical margin is a strong predictor of recurrence and eventual death from urothelial carcinoma of the bladder. Soft tissue surgical margin status should always be reported in the pathological reports after radical cystectomy. Due to uniformly poor outcomes patients with positive soft tissue surgical margins should be considered for studies on adjuvant local and/or systemic therapy.

Stage pT0 at radical cystectomy confers improved survival: an international study of 4,430 patients.

PURPOSE: We describe the cancer related outcome in patients with pT0 bladder urothelial carcinoma at radical cystectomy who did not receive preoperative chemotherapy in a large multicenter series. We also compared outcomes in patients with pT0 bladder urothelial carcinoma to those in patients with other stages and assessed the effect of clinical stage on outcome. MATERIALS AND METHODS: We reviewed the records of 4,430 patients treated with radical cystectomy for bladder urothelial carcinoma without neoadjuvant chemotherapy at 12 centers in the United States, Canada and Europe. RESULTS: Of the patients 228 (5.1%) had pT0 disease at radical cystectomy. Clinical stage was cTa or cTis in 13.6% and cT1 in 29.8% of these patients, and disease was muscle invasive (cT2-4a) in 56.2%. Metastasis developed to regional lymph nodes in 17 cases (7.5%). At a median 48.2-month followup 15 patients (6.6%) had died of bladder cancer. Five-year recurrence-free and cancer specific survival estimates were 89.7% (95% CI 85.3-93.1) and 93.1% (95% CI 88.9-95.6), respectively. Disease-free and cancer specific survival in pT0 cases was similar to that in pTa/pTis cases but significantly better than in pT1 or pT2 cases. On multivariate analysis increased disease recurrence and cancer specific mortality risks were significantly associated with lymph node metastasis (each p <0.001) and female gender (p <0.001 and 0.013, respectively). CONCLUSIONS: Although stage pT0 at radical cystectomy confers a benefit in survival, some patients experience disease recurrence and eventual death. Identifying these patients may help tailor postoperative decision making in patients with pT0.

Characteristics and outcomes of patients with clinical carcinoma in situ only treated with radical cystectomy: an international study of 243 patients.

PURPOSE: We describe the rate of up staging and the cancer specific outcomes of patients with carcinoma in situ refractory to transurethral resection with intravesical therapy treated with radical cystectomy. MATERIALS AND METHODS: The records of 3,207 patients treated with radical cystectomy for urothelial carcinoma of the bladder at 8 centers in the United States, Canada and Europe were reviewed. RESULTS: Of the 3,207 patients who underwent radical cystectomy 243 (7.6%) had clinical carcinoma in situ only disease before radical cystectomy. At radical cystectomy 117 patients (48.1%) had carcinoma in situ only, 20 (8.2%) had pT0 urothelial carcinoma of the bladder, 19 (7.8%) had pTa urothelial carcinoma of the bladder and 36% had disease up staged (32 [13.2%] pT1, 29 [11.9%] pT2, 12 [4.9%] pT3 and 14 [5.8%] pT4). A total of 22 patients (9.1%) had lymphovascular invasion in the radical cystectomy specimen and 14 (5.8%) had metastasis to regional lymph nodes. Overall 5-year recurrence-free and cancer specific survival estimates were 74% (95% CI 68-79) and 85% (95% CI 80-89), respectively. On multivariable analysis adjusting for the effects of standard predictors, lymph node metastasis and lymphovascular invasion were associated with an increased risk of disease recurrence (p = 0.017 and p = 0.043, respectively) and cancer specific mortality (p = 0.019 and p = 0.001, respectively). Female gender was an independent risk factor for cancer specific mortality (p = 0.029) but not for disease recurrence (p = 0.173). CONCLUSIONS: Approximately a fourth of patients treated with radical cystectomy for clinical carcinoma in situ only had muscle invasive disease and 5.8% had metastasis to regional lymph nodes. Identification of those patients with a potentially aggressive natural history of carcinoma in situ is of the utmost importance as they are likely to benefit from early radical cystectomy.

Characteristics and outcomes of patients with pT4 urothelial carcinoma at radical cystectomy: a retrospective international study of 583 patients.

PURPOSE: We describe cancer specific outcomes in patients with pT4 bladder urothelial carcinoma at radical cystectomy in a large international cohort. MATERIALS AND METHODS: We reviewed the records of 4,257 patients treated with radical cystectomy for bladder urothelial carcinoma at 12 centers. No patient received any preoperative systemic chemotherapy or radiotherapy. RESULTS: Of the 4,257 patients 583 (14%) had pT4 bladder urothelial carcinoma, of whom 83.7% were male, 85.2% had substage pT4a disease, 24.9% had positive soft tissue surgical margins, 57.8% had lymphovascular invasion and 53.5% had lymph node metastasis. Median followup was 55.0 months. Overall estimated 5-year recurrence-free and cancer specific survival was 29% (95% CI 22-32) and 31% (95% CI 25-36), respectively. On multivariate analysis female gender (p = 0.005 and p = 0.001), positive soft tissue surgical margins (p = 0.014 and p <0.001), lymphovascular invasion (p = 0.016 and p = 0.005), pT4b substage (p = 0.041 and p = 0.002, respectively) and lymph node involvement (each p <0.001) were independently associated with disease recurrence and cancer specific mortality. CONCLUSIONS: Patients with pT4 bladder urothelial carcinoma have highly variable outcomes. Features associated with metastatic tumor dissemination (ie lymph node invasion and lymphovascular invasion) and local disease burden (ie soft tissue surgical margins and pT4 substage) are associated with poor outcomes in patients with pT4 bladder urothelial carcinoma. Further research is needed to understand why female patients with pT4 bladder urothelial carcinoma have a worse outcome than their male counterparts.