Three Different Learning Curves Have an Independent Impact on Perioperative Outcomes After Robotic Partial Nephrectomy: A Comparative Analysis.

BACKGROUND: Robot-assisted partial nephrectomy (RAPN) has become widely accepted, but its different underlying types of learning curves have not been comparatively analyzed to date. This study aimed to determine and compare the impact that the learning curve of the department, the console surgeon, and the bedside assistant as well as patient-related factors has on the perioperative outcomes of RAPN. METHODS: The study retrospectively analyzed 500 consecutive transperitoneal RAPNs (2007-2018) performed in a tertiary referral center by 7 surgeons and 37 bedside assistants. Patient characteristics and surgical data were obtained. Experience (EXP) was defined as the current number of RAPNs performed by the department, the surgeon, and the assistant. As the primary outcome, the impact of EXP and patient-related factors on perioperative outcomes were analyzed and compared. As the secondary outcome, a cutoff between "experienced" and "inexperienced" was defined. Correlation and regression analysis, receiver operating characteristic curve analysis, Fisher's exact test, and the Mann-Whitney U test were performed, with p values lower than 0.05 denoting significance. RESULTS: The EXP of the department, the surgeon, and the assistant each has a major influence on perioperative outcome in RAPN irrespective of patient-related factors. Perioperative outcomes improve significantly with EXP greater than 100 for the department, EXP greater than 35 for the surgeon, and EXP greater than 15 for the assistant. CONCLUSIONS: The perioperative results of RAPN are influenced by three different types of learning curves including those for the surgical department, the console surgeon, and the assistant. The influence of the bedside assistant clearly has been underestimated to date because it has a significant impact on the perioperative outcomes of RAPN.

Can local treatment prolong the sensitivity of metastatic prostate cancer to androgen deprivation or even prevent castration resistance?

PURPOSE: A number of observational clinical studies suggest that prior primary tumor treatment favorably influences the course of metastatic prostate cancer (PCa), but its mechanisms of action are still speculative. Here, we describe the long-lasting sensitivity to various forms of androgen deprivation in patients after radical prostatectomy (RP) for locally advanced PCa as one potential mechanism. METHODS: A consecutive series of 115 radical prostatectomies after inductive therapy for T4 prostate cancer was re-analyzed, and long-term survival, as well as recurrence patterns and responses to different forms of hormonal manipulation, were assessed. RESULTS: The estimated biochemical response-free, PCa-specific, and overall survival rates after 200 months were 20%, 65%, and 47% with a median overall survival of 156 months. The majority of patients, although not cured of locally advanced PCa (84/115), showed long-term survival after RP. PCa-specific and overall survival rates of these 84 patients with biochemical recurrence were 61% and 44% at 150 months. Long-term sensitivity to ADT was found to be the main reason for the favorable tumor-specific survival in spite of biochemical recurrence. CONCLUSIONS: Sensitivity to primary or secondary hormonal manipulation was the main reason for the long-term survival of patients who had not been cured by surgery only. The results suggest that treatment of the primary tumor-bearing prostate delays castration-resistant PCa and enhances the effect of hormonal therapies in a previously unknown manner. The underlying cellular and molecular mechanisms need to be explored in more detailed analyses, which could profoundly impact treatment concepts of locally advanced and metastatic PCa.

4-miRNA Score Predicts the Individual Metastatic Risk of Renal Cell Carcinoma Patients.

BACKGROUND: In order to improve individual prognostication as well as stratification for adjuvant therapy in patients with clinically localized clear cell renal cell carcinoma (ccRCC), reliable prognostic biomarkers are urgently needed. In this study, microRNAs (miRNAs) have emerged as promising candidates. We investigated whether a combination of differently expressed miRNAs in primary tumors can predict the individual metastatic risk. METHODS: Using two prospectively collected biobanks of academic centers, 108 ccRCCs were selected, including 57 from patients with metastatic disease at diagnosis or during follow-up and 51 without evidence of metastases. Fourteen previously identified candidate miRNAs were tested in 20 representative formalin-fixed and paraffin embedded samples in order to select the best discriminators between metastatic and nonmetastatic ccRCC. These miRNAs were approved in 108 tumor samples. We evaluated the association of altered miRNA expression with the metastatic potential of tumors using quantitative polymerase chain reaction. A prognostic 4-miRNA model has been established using a random forest classifier. Cox regression analyses were performed for correlation of the miRNA model and clinicopathological parameters to metastasis-free and overall survival. RESULTS: Nine miRNAs indicated significant expression alterations in the small cohort. These miRNAs were validated in the whole cohort. The established 4-miRNA score (miR-30a-3p/-30c-5p/-139-5p/-144-5p) has been identified as a superior predictor for metastasis-free survival (hazard ratio 12.402; p = 7.0E-05) and overall survival (p = 1.1E-04) compared with clinicopathological parameters, and likewise in the Leibovich score subgroups. CONCLUSIONS: We identified a 4-miRNA model that was found to be superior to clinicopathological parameters in accurately predicting individual metastatic risk and can support patient selection for risk-stratified follow-up and adjuvant therapy studies.

Radical prostatectomy in T4 prostate cancer after inductive androgen deprivation: results of a single-institution series with long-term follow-up.

OBJECTIVES: To determine the outcomes of complete surgical resection of T4 prostate cancer after inductive androgen-deprivation therapy (ADT), as inductive ADT and subsequent radical prostatectomy (RP) is not recommended by any guideline yet. PATIENTS AND METHODS: A monocentric RP database was queried for patients initially diagnosed with T4 prostate cancer, considered primarily as inoperable because of a fixed mass defined by rectal examination in combination with high PSA level and/or large foci of biopsy confirmed undifferentiated prostate cancer. Treatment consisted of primary ADT until PSA nadir with consecutive RP. Patients underwent retropubic RP (RRP) or robot-assisted laparoscopic RP (RALP) after inductive ADT until achievement of the PSA nadir, which is in general reached after 6-7 months. The intraoperative course and complications were analysed. Finally, Kaplan-Meier estimates were calculated for overall survival (OS) and prostate cancer-specific survival (PCSS). RESULTS: We retrospectively identified 116 patients treated between 2000 and 2014. At diagnosis, the median (range) PSA level was 37.6 (2.44-284) ng/mL. The preoperative median (range) PSA after inductive ADT was 0.73 (0.01-34) ng/mL. Thereafter, patients underwent RRP or, since 2006, RALP. The median (95% confidence interval) OS was 156 (118.9-193.1) months. The PCSS at 150 months was 82%. CONCLUSIONS: Surgical therapy of primarily inoperable prostate cancer is feasible and safe after inductive ADT. The OS of this cohort seems comparable with results described for patients with primary operable high-risk prostate cancer.

Segmental Testicular Infarction: Case Series and Literature Review of a Rare Diagnosis in Men with Acute Testicular Pain.

The incidence of segmental testicular infarction (STI) is very low. Such a disorder most often affects young men. The most common symptom is sudden testicular pain. We report 6 cases of men diagnosed with STI. Clinical examination, blood test, urine analysis, and ultrasound examination with colour Doppler were performed. Furthermore, tissue sonoelastography or MRI was performed in selected patients. All men underwent surgical exploration. In all but one man, the affected testis was preserved. Although STI is a rare condition, it should be taken into account if testicular pain prior to suspicious ultrasound imaging occurs. To be aware of this benign testicular pathology and its clinical and imaging features is important to avoid unnecessary orchiectomies in young patients.

Robot-assisted vs open adrenalectomy: evaluation of cost-effectiveness and peri-operative outcome.

OBJECTIVES: To compare robot-assisted laparoscopic adrenalectomy (RALA) and open adrenalectomy (OA) with regard to intra-operative complications, peri-operative outcome and cost effectiveness. SUBJECTS AND METHODS: Functional and statistical data from patients who underwent OA or RALA between 2001 and 2015 were prospectively recorded including intra- and postoperative outcomes. Data on per-day costs from current census reports (€540/day and €1 145/day for normal and intermediate care [IMC]) were also used to evaluate treatment costs. Additional costs for RALA were assumed at €2288 as reported in the current literature. Patients were matched by American Society of Anesthesiologists score, age, side of surgery and gender for comparison of OA and RALA. A total of 28 matched pairs were analysed with regard to patient characteristics, peri-operative outcomes and cost-effectiveness. Statistical significance of outcome variables was determined using Student's t-test and Pearson's chi-squared test. RESULTS: As a result of the matching process, patient groups did not differ in their main characteristics. Length of hospital stay was shorter for RALA than for OA (11.1 ± 4.8 vs 6.8 ± 1.2 days; P < 0.01) as was IMC treatment (2.3 ± 1.7 vs 1.2 ± 0.4 days; P < 0.01). The mean operating time was longer for RALA (128.5 ± 46.5 vs 102.2 ± 44.5 min; P = 0.03), but the last 10 RALA procedures (mean: 97.1 ± 35.2 min) were similar to OA. The rate of complications was similar in the two groups. Estimated costs were €8 627.5 for OA and €7 334 for RALA. CONCLUSIONS: The study showed that RALA was safe and cost-effective compared with OA. Increasing experience leads to similar operating times, putting high-volume centres at an advantage.

Development of a standardised training curriculum for robotic surgery: a consensus statement from an international multidisciplinary group of experts.

OBJECTIVES: To explore the views of experts about the development and validation of a robotic surgery training curriculum, and how this should be implemented. MATERIALS AND METHODS: An international expert panel was invited to a structured session for discussion. The study was of a mixed design, including qualitative and quantitative components based on focus group interviews during the European Association of Urology (EAU) Robotic Urology Section (ERUS) (2012), EAU (2013) and ERUS (2013) meetings. After introduction to the aims, principles and current status of the curriculum development, group responses were elicited. After content analysis of recorded interviews generated themes were discussed at the second meeting, where consensus was achieved on each theme. This discussion also underwent content analysis, and was used to draft a curriculum proposal. At the third meeting, a quantitative questionnaire about this curriculum was disseminated to attendees to assess the level of agreement with the key points. RESULTS: In all, 150 min (19 pages) of the focus group discussion was transcribed (21 316 words). Themes were agreed by two raters (median agreement κ 0.89) and they included: need for a training curriculum (inter-rater agreement κ 0.85); identification of learning needs (κ 0.83); development of the curriculum contents (κ 0.81); an overview of available curricula (κ 0.79); settings for robotic surgery training ((κ 0.89); assessment and training of trainers (κ 0.92); requirements for certification and patient safety (κ 0.83); and need for a universally standardised curriculum (κ 0.78). A training curriculum was proposed based on the above discussions. CONCLUSION: This group proposes a multi-step curriculum for robotic training. Studies are in process to validate the effectiveness of the curriculum and to assess transfer of skills to the operating room.

Pembrolizumab plus Abiraterone Acetate and Prednisone in Patients with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Results from KEYNOTE-365 Cohort D.

BACKGROUND AND OBJECTIVE: Abiraterone acetate (abiraterone) plus prednisone is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Our aim was to evaluate the efficacy and safety of pembrolizumab plus abiraterone in mCRPC. METHODS: In cohort D of the phase 1b/2 KEYNOTE-365 study (NCT02861573), patients were chemotherapy-naïve, had disease progression ≤6 mo before screening, and had either not received prior next-generation hormonal agents for mCRPC or had received prior enzalutamide for mCRPC and had disease progression or became intolerant to enzalutamide. Patients received pembrolizumab 200 mg intravenously every 3 wk plus abiraterone 1000 mg orally once daily and prednisone 5 mg orally twice daily. The primary endpoints were safety, prostate-specific antigen (PSA) response rate, and objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary endpoints included radiographic progression-free survival (rPFS) according to Prostate Cancer Clinical Trials Working Group 3-modified RECIST v1.1 by BICR and overall survival (OS). KEY FINDINGS AND LIMITATIONS: For the 103 patients who were treated, median follow-up was 28 mo (interquartile range 26-31). The confirmed PSA response rate was 56% (58/103 patients). The ORR for patients with RECIST v1.1-measurable disease was 16% (6/37 patients). Median rPFS was 15 mo (95% confidence interval 9.2-22) and median OS was 30 mo (95% confidence interval 23-not reached); the estimated 24-mo OS rate was 58%. In total, 91% of patients experienced treatment-related adverse events, and 39% experienced grade 3-5 events. Grade 3/4 elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) was observed in 12% and 6.8% of patients, respectively. One patient died due to treatment-related myasthenic syndrome. Study limitations include the single-arm design. CONCLUSIONS: Pembrolizumab plus abiraterone and prednisone demonstrated antitumor activity and acceptable safety in patients with chemotherapy-naïve mCRPC. Higher incidence of grade 3/4 elevated ALT/AST occurred than was reported for the individual agents. PATIENT SUMMARY: For patients with metastatic castratation-resistant prostate cancer, the drug combination of pembrolizumab plus abiraterone and prednisone showed antitumor activity and acceptable safety.

Adjuvant vs. progression-triggered treatment with gemcitabine in platinum-ineligible high-risk bladder cancer patients: Long-term follow-up of a randomized phase 3 trial.

BACKGROUND: Cisplatin-based chemotherapy (ChT) is the preferred perioperative treatment in muscle-invasive urothelial carcinoma of the urinary bladder (UCUB). Nevertheless, a certain number of patients are ineligible for platinum-based ChT. This trial compared immediate adjuvant vs. delayed gemcitabine ChT at progression in platinum-ineligible patients with high-risk UCUB. METHODS: High-risk platinum-ineligible UCUB patients (n = 115) were randomized 1:1 to adjuvant gemcitabine (n = 59) or gemcitabine at progression (n = 56). Overall survival was analyzed. Additionally, we analyzed progression-free survival (PFS), toxicity and quality of life (QoL). RESULTS: After a median follow-up of 3.0 years (inter quartile range [IQR]: 1.3-11.6), adjuvant ChT did not significantly prolong overall survival (OS) (HR: 0.84; 95% CI: 0.57-1.24; P = 0.375), with 5-year OS of 44.1% (95% CI: 31.2-56.2) and 30.4% (95% CI: 19.0-42.5), respectively. We noted no significant difference in PFS (HR: 0.76; 95% CI: 0.49-1.18; P = 0.218), with 5-year PFS of 36.2% (95% CI: 22.8-49.7) in the adjuvant group and 22.2% (95% CI: 11.5%-35.1%) when treated at progression. Patients with adjuvant treatment showed a significantly worse QoL. The trial was prematurely closed after recruitment of 115 of the planned 178 patients. CONCLUSIONS: There was no statistically significant difference in terms of OS and PFS for patients with platinum-ineligible high-risk UCUB receiving adjuvant gemcitabine compared to patients treated at progression. These findings underline the importance of implementing and developing new perioperative treatments for platinum-ineligible UCUB patients.

Robot-assisted Radical Cystectomy with Orthotopic Neobladder Reconstruction: Techniques and Functional Outcomes in Males.

BACKGROUND: Little is known regarding functional outcomes after robot-assisted radical cystectomy (RARC) and intracorporeal neobladder (ICNB) reconstruction. OBJECTIVE: To report on urinary continence (UC) and erectile function (EF) at 12 mo after RARC and ICNB reconstruction and investigate predictors of these outcomes. DESIGN, SETTING, AND PARTICIPANTS: We used data from a multi-institutional database of patients who underwent RARC and ICNB reconstruction for bladder cancer. SURGICAL PROCEDURE: The cystoprostatectomy sensu stricto followed the conventional steps. ICNB reconstruction was performed at the physician's discretion according to the Studer/Wiklund, S pouch, Gaston, vescica ileale Padovana, or Hautmann technique. The techniques are detailed in the video accompanying the article. MEASUREMENTS: The outcomes measured were UC and EF at 12 mo. RESULTS AND LIMITATIONS: A total of 732 male patients were identified with a median age at diagnosis of 64 yr (interquartile range 58-70). The ICNB reconstruction technique was Studer/Wiklund in 74%, S pouch in 1.5%, Gaston in 19%, vescica ileale Padovana in 1.5%, and Hautmann in 4% of cases. The 12-mo UC rate was 86% for daytime and 66% for nighttime continence, including patients who reported the use of a safety pad (20% and 32%, respectively). The 12-mo EF rate was 55%, including men who reported potency with the aid of phosphodiesterase type 5 inhibitors (24%). After adjusting for potential confounders, neobladder type was not associated with UC. Unilateral nerve-sparing (odds ratio [OR] 3.85, 95% confidence interval [CI] 1.88-7.85; p < 0.001) and bilateral nerve-sparing (OR 6.25, 95% CI 3.55-11.0; p < 0.001), were positively associated with EF, whereas age (OR 0.93, 95% CI 0.91-0.95; p < 0.001) and an American Society of Anesthesiologists score of 3 (OR 0.46, 95% CI 0.25-0.89; p < 0.02) were inversely associated with EF. CONCLUSIONS: RARC and ICNB reconstruction are generally associated with good functional outcomes in terms of UC. EF is highly affected by the degree of nerve preservation, age, and comorbidities. PATIENT SUMMARY: We investigated functional outcomes after robot-assisted removal of the bladder in terms of urinary continence and erectile function. We found that, in general, patients have relatively good functional outcomes at 12 months after surgery.

Clinical differences in daytime wetting subtypes: urge incontinence and postponed voiding.

PURPOSE: Urge incontinence and voiding postponement are common subtypes of daytime wetting in children. We analyzed clinical and behavioral differences in children with urge incontinence, voiding postponement and healthy controls at 2 centers. MATERIALS AND METHODS: A total of 49 consecutive children 5 to 13 years old with urge incontinence (22) or voiding postponement (27) who presented to the department of urology or child psychiatry were examined as well as 32 age and gender matched controls. Instruments included physical examination, sonography, uroflowmetry, urinalysis, a 48-hour bladder diary, the Child Behavior Checklist, a structured psychiatric interview and an intelligence test. RESULTS: The incontinent group consisted of 28 boys and 21 girls with a mean age of 7.35 years. Controls included 13 girls and 19 boys with a mean age of 7.31 years. Incontinent children had a higher rate of pathological uroflow curves (33% vs 25%) and urinary tract infection (6% vs 3%), greater post-void residual volume (6.3 ml vs 3.8 ml) and a thicker bladder wall. Mean IQ was the same in the 2 groups (103). The Child Behavior Checklist showed that significantly more incontinent children had clinical total behavior (41% vs 9%, p <0.01), and externalizing (35% vs 0%, p <0.001) and internalizing (29% vs 6%, p <0.05) scores than controls. Also, more children with voiding postponement had total clinical scores than those with urinary incontinence (56% vs 24%, p <0.05). Of incontinent children 49% fulfilled the criteria for at least 1 ICD-10 psychiatric diagnosis vs 9% of controls (p <0.001). There were no differences between children recruited at the departments of urology and child psychiatry. CONCLUSIONS: This study shows that urge incontinence and voiding postponement are significantly associated with somatic complaints and psychological abnormalities compared to a control population. Children with voiding postponement have more externalizing behavioral disorders. Children seen at urological departments carry the same psychiatric risks and require the same attention to behavioral problem diagnosis.

Serum concentrations of folate vitamers in patients with a newly diagnosed prostate cancer or hyperplasia.

BACKGROUND: Folate is required for synthesis of methyl groups and DNA in growing cells. The association between folate and prostate cancer (PCa) is not conclusive. METHODS: We investigated concentrations of folate vitamers, S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) in blood of men with PCa (n = 129) or benign prostatic hyperplasia (BPH) (n = 73) who were recruited just after the first diagnosis. RESULTS: In younger subjects <65 years, concentrations of (6S)-5-CH3-H4folate (15.3 vs. 17.7 nmol/L) or total folate (UPLC-MS/MS) (18.7 vs. 23.0 nmol/L) did not differ between men with BPH and those with PCa, while SAM was higher in the controls (128 vs. 116 nmol/L). Younger patients with low- and high grade cancer did not differ in (6S)-5-CH3-H4folate (17.8 vs. 17.3 nmol/L) or total folate (UPLC-MS/MS) (22.9 vs. 23.3 nmol/L), but SAM was lower in patients with low grade PCa (111 vs. 126 nmol/L). In the older group ≥65 years, (6S)-5-CH3-H4folate (18.4 vs. 18.2 nmol/L) and total folate (UPLC-MS/MS) (22.5 vs. 22.1 nmol/L) did not differ between BPH and PCa. Older patients with advanced tumors had lower (6S)-5-CH3-H4folate compared with those with low grade tumor (12.8 vs. 20.0 nmol/L: p = 0.013). Plasma SAM was not different between older patients and controls and was not related to PCa grade. CONCLUSIONS: Lowered serum methyl folate measured at the time of diagnosis in older patients with advanced PCa, and lowered plasma SAM in younger patients with low grade PCa suggest differential folate metabolism that may have mechanistic, prognostic or predictive values.

Choline-phospholipids inter-conversion is altered in elderly patients with prostate cancer.

BACKGROUND: Choline is an important source of phospholipids and methyl groups in mammalian cells. High demands for methyl and phospholipids in malignant cells suggest that choline metabolism may be disturbed in patients with cancer. OBJECTIVES AND METHODS: This case-control study investigated differences in concentrations of choline metabolites between 80 elderly men (age ≥ 65 years) with prostate cancer (PCa) and 51 men with benign prostatic hyperplasia (BPH). Plasma/serum concentrations of free choline, betaine, dimethylglycine, folate, total homocysteine (tHcy), cystathionine, methylmalonic acid, S-adenosyl homocysteine (SAH), S-adenosyl methionine (SAM), and phospholipids were measured. RESULTS: Men with BPH and those with PCa showed no significant differences in the concentrations of free choline (median = 9.7 vs. 10.0 µmol/L), folate (17.4 vs. 19.8 nmol/L), tHcy (16.0 vs. 16.2 µmol/L), SAH (18.8 vs. 18.2 nmol/L), and phosphatidylcholine (1634 vs. 1610 µmol/L). The concentrations of methylmalonic acid were lower in men with PCa (203 vs. 228 nmol/L) but the difference was not significant after adjusting for age. Sphingomyelin species (16:0, 18:0, 18:1, 20:0, 22:0, 22; 1, 23:0, 23:1, 24:0, 24:1, and 24:2) were significantly lower in men with PCa than in the controls (6-16% differences). Multiple regression analyses showed that the presence of PCa, statin use, choline, age, cystathionine, and methylmalonic acid were significant negative determinant of sphingomyelins, whereas phosphatidylcholine was a strong positive determinant. CONCLUSIONS: The current results support systemic alterations in phospholipids metabolism in PCa. We report on a significant decrease in plasma concentrations of sphingomyelin in elderly patients with PCa and in users of statins. The PCa-associated low sphingomyelin showed a synergy with the effect of statins. The presence of PCa was not associated with significant changes in plasma concentrations of choline or methyl metabolites. However, changes in choline absorption and tissue uptake cannot be ruled out in this study.

Long-term oncologic outcomes following robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium.

BACKGROUND: Long-term oncologic data on patients undergoing robot-assisted radical cystectomy (RARC) are limited and based largely on single-institution series. OBJECTIVE: Report survival outcomes of patients who underwent RARC ≥5 yr ago. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of the prospectively populated International Robotic Cystectomy Consortium multi-institutional database identified 743 patients with RARC performed ≥5 yr ago. Clinical, pathologic, and survival data at the latest follow-up were collected. Patients with palliative RARC were excluded. Final analysis was performed on 702 patients from 11 institutions in 6 countries. INTERVENTION: RARC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes of interest, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were plotted using Kaplan-Meier survival curves. A Cox proportional hazards model was used to identify factors that predicted outcomes. RESULTS AND LIMITATIONS: Pathologic organ-confined (OC) disease was found in 62% of patients. Soft tissue surgical margins (SMs) were positive in 8%. Median lymph node (LN) yield was 16, and 21% of patients had positive LNs. Median follow-up was 67 mo (interquartile range: 18-84 mo). Five-year RFS, CSS, and OS were 67%, 75%, and 50%, respectively. Non-OC disease and SMs were associated with poorer RFS, CSS, and OS on multivariable analysis. Age predicted poorer CSS and OS. Adjuvant chemotherapy and positive SMs were predictors of RFS (hazard ratio: 3.20 and 2.16; p<0.001 and p<0.005, respectively). Stratified survival curves demonstrated poorer outcomes for positive SM, LN, and non-OC disease. Retrospective interrogation and lack of contemporaneous comparison groups that underwent open radical cystectomy were major limitations. CONCLUSIONS: The largest multi-institutional series to date reported long-term survival outcomes after RARC. PATIENT SUMMARY: Patients who underwent robot-assisted radical cystectomy for bladder cancer have acceptable long-term survival.

Comprehensive genotypic analysis of human prostate cancer cell lines and sublines derived from metastases after orthotopic implantation in nude mice.

We recently reported on a prostate cancer progression model which was based on repeated orthotopic implantation of human prostate cancer cell lines into athymic nude mice leading to an increase of tumor cell aggressiveness. To assess progression-associated clonal evolution of genotypic changes, we now performed comparative cytogenetic characterization of the original cell lines DU145 and PC3 with derived sublines DU145MN1 and PC3-N. Cell line PC3-125-1L, isolated from a lung metastasis after subcutaneous inoculation of PC3 into nude mice, was included in the study. Whole-genome analysis was performed using spectral karyotyping and comparative genomic hybridization. Fluorescence in situ hybridization was used to assess amplification of selected genes, which are supposed to play a role in prostate cancer progression. Differences in the genetic constitution between parental cell lines and sublines involved gains of genetic material at 2q, 5q, 12p/q, and 18p as well as losses at 6p, 7q, 17p, 18q, and 22q. Loss of 17p in DU145MN1 and high-level amplification of MYC in PC3-125-1L resulted in loss of p53 expression and upregulation of Myc expression, respectively, as was assessed by Western blotting. Thus, the nude mice model is very useful to follow clonal evolution of genetic changes during increase of prostate cancer aggressiveness and possibly to clone genes associated with the progression of prostate cancer.

Evidence for gains at 15q and 20q in brain metastases of prostate cancer.

Many detailed genetic studies have been reported on prostate carcinogenesis. A major shortcoming of these studies, however, is the fact that most data have been gained from investigations that were performed at a single point of time during tumor development. Only little is known on the dynamic process of genetic changes during the course of the disease. We performed comparative genomic hybridization in two cases of prostate cancer brain metastases. Tissue samples from the primary tumors, the locally recurrent tumor in one case, and the brain metastases from both cases were available for analysis. The number of chromosome abnormalities was found to be increased in the metastases. This contrasts to a remarkably stable chromosome composition of the primary tumor over several years, even in an androgen-depleted environment. When focusing on these changes, which either emerged as new common aberrations in both brain metastases, or which were commonly present in the primary and metastatic tumors, we were able to delineate five chromosomal sites that are assumed to be related to prostate cancer metastasis: 8q21 approximately q22, 8q24, 15q24 approximately q26, 20q12 approximately q13.1, and Xq12 approximately q21. These findings provide new evidence for a putative role of genes at 15q and 20q in the metastatic process of prostate cancer.

Enzalutamide in castration-resistant prostate cancer patients progressing after docetaxel and abiraterone.

BACKGROUND: Abiraterone, an androgen synthesis inhibitor, has been successfully used in the treatment of castration-resistant prostate cancer (CRPC) for 2 yr. Enzalutamide is a second-generation nonsteroidal antiandrogen that has recently been approved for the same indication. OBJECTIVE: This is the first study to evaluate the effectiveness of enzalutamide after failure of abiraterone. DESIGN, SETTING, AND PARTICIPANTS: Thirty-five patients were identified as having received sequential therapy with abiraterone followed by enzalutamide. All patients had undergone prior docetaxel chemotherapy, and no patient had received ketoconazole. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Posttreatment changes in prostate-specific antigen (PSA) were used to determine the activity of enzalutamide in patients who had received prior abiraterone. RESULTS AND LIMITATIONS: The median duration of abiraterone treatment was 9.0 mo (range: 2.0-19.0 mo). Of the 35 patients, 16 (45.7%) achieved a >50% decline in PSA, and 14 (40%) had a rising PSA as the best response. The median duration of subsequent enzalutamide treatment was 4.9 mo (Kaplan-Meier estimate; 95% confidence interval [CI], 2.4-7.4). Seven of 16 CRPC patients who were initially abiraterone-sensitive (43.8%) and 3 of 19 CRPC patients who were initially abiraterone-insensitive (15.8%) showed a >50% PSA decline while taking enzalutamide. Of the 35 patients, 17 (48.6%) were primarily enzalutamide-resistant and showed a rising PSA as the best response. Median time to progression was 4.0 mo (95% CI, 2.0-6.0) for 18 of 35 patients with at least one declining PSA value while taking enzalutamide (51.4%). Of the 17 patients who were assessable radiologically, only 1 (2.9%) attained a confirmed partial response. Small sample size was the major limitation. CONCLUSIONS: Enzalutamide treatment achieved only a modest response rate in patients progressing after abiraterone. Although cross-resistance between abiraterone and enzalutamide was a common phenomenon, it was not inevitable, and a small but significant number of patients showed significant benefit from sequential treatment.

Analysis of intracorporeal compared with extracorporeal urinary diversion after robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium.

BACKGROUND: Intracorporeal urinary diversion (ICUD) has the potential benefits of a smaller incision, reduced pain, decreased bowel exposure, and reduced risk of fluid imbalance. OBJECTIVE: To compare the perioperative outcomes of patients undergoing extracorporeal urinary diversion (ECUD) and ICUD following robot-assisted radical cystectomy (RARC). DESIGN, SETTING, AND PARTICIPANTS: We reviewed the database of the International Robotic Cystectomy Consortium (IRCC) (18 international centers), with 935 patients who had undergone RARC and pelvic lymph node dissection (PLND) between 2003 and 2011. INTERVENTION: All patients within the IRCC underwent RARC and PLND as indicated. The urinary diversion was performed either intracorporeally or extracorporeally. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Demographic data, perioperative outcomes, and complications in patients undergoing ICUD or ECUD were compared. All patients had at least a 90-d follow-up. The Fisher exact test was used to summarize categorical variables and the Wilcoxon rank sum test or Kruskal-Wallis test for continuous variables. RESULTS AND LIMITATIONS: Of 935 patients who had RARC and PLND, 167 patients underwent ICUD (ileal conduit: 106; neobladder: 61), and 768 patients had an ECUD (ileal conduit: 570; neobladder: 198). Postoperative complications data were available for 817 patients, with a minimum follow-up of 90 d. There was no difference in age, gender, body mass index, American Society of Anesthesiologists grade, or rate of prior abdominal surgery between the groups. The operative time was equivalent (414 min), with the median hospital stay being marginally longer for the ICUD group (9 d vs 8 d, p=0.086). No difference in the reoperation rates at 30 d was noted between the groups. The 90-d complication rate was not significant between the two groups, but a trend favoring ICUD over ECUD was noted (41% vs 49%, p=0.05). Gastrointestinal complications were significantly lower in the ICUD group (p ≤ 0.001). Patients with ICUD were at a lower risk of experiencing a postoperative complication at 90 d (32%) (odds ratio: 0.68; 95% confidence interval, 0.50-0.94; p=0.02). Being a retrospective study was the main limitation. CONCLUSIONS: Robot-assisted ICUD can be accomplished safely, with comparable outcomes to open urinary diversion. In this cohort, patients undergoing ICUD had a relatively lower risk of complications.