Assessment of the oncological outcomes of three different bacillus Calmette-Guérin strains in patients with high-grade T1 non-muscle-invasive bladder cancer.

OBJECTIVE: : To determine whether there are significant differences in oncological outcomes between three different bacillus Calmette-Guérin (BCG) strains used for adjuvant intravesical immunotherapy in patients with high-grade T1 (T1HG) non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: : Data of 590 patients with a diagnosis of primary T1HG NMIBC were retrospectively reviewed. The study included 138 (23.4%) patients who were treated with the Moreau, 272 (46.1%) with the TICE, and 180 (30.5%) with the RIVM strains. All patients included in the analysis received at least five instillations of an induction course and at least two installations of a maintenance course. Due to existing differences in baseline patient characteristics, the association between oncological outcomes and strain groups was investigated by complementary analysis with the implementation of inverse probability weighting (IPW). RESULTS: : The 5-year recurrence-free survival (RFS) rate was 70.5%, 66.7% and 55.2% for the Moreau, TICE and RIVM groups, respectively (P = 0.016). The 5-year progression-free survival (PFS) rates were 84.4%, 85% and 77.8% in the Moreau, TICE and RIVM groups, respectively (P = 0.215). The IPW-adjusted Cox proportional hazard regression analysis did not show any differences in RFS between the Moreau and TICE groups (P = 0.69), whereas the RIVM strain was significantly associated with worse RFS compared to the Moreau (hazard ratio [HR] 1.69 for RIVM; P = 0.034) and TICE (HR 1.87 for RIVM; P = 0.002) strains. The IPW-adjusted analysis did not show any significant differences between study groups in terms of PFS. CONCLUSIONS: : The results of the present study suggest that the Moreau and TICE strains might be superior to the RIVM strain in terms of RFS in patients with T1HG NMIBC.Abbreviations: CIS: carcinoma in situ; IPW: inverse probability weighting; IQR: interquartile range; HR: hazard ratio; HG: high grade; LVI: lymphovascular invasion; MP: muscularis priopria; NMIBC: non-muscle-invasive bladder cancer; PFS: progression-free survival; RCT: randomised controlled trial; RFS: recurrence-free survival; T1HG, high-grade T1; (re-)TURB: (re-staging) transurethral resection of bladder; VH: variant histology.

The Cancer of the Bladder Risk Assessment (COBRA) score for estimating cancer-specific survival after radical cystectomy: external validation in a large bi-institutional cohort.

OBJECTIVE: To perform an external validation of the Cancer of the Bladder Risk Assessment (COBRA) score for estimating cancer-specific survival (CSS) after radical cystectomy (RC) in a large bi-institutional cohort of patients. PATIENTS AND METHODS: Patients treated with RC and lymph node dissection (LND) between May 1996 and July 2017 were retrieved from the RC databases of Leuven and Turin. Collected variables were age at RC, tumour stage, lymph node (LN) density, neoadjuvant chemotherapy, the extent of LND, and nodal stage. The primary outcome was CSS visualised using Kaplan-Meier plots. Cox proportional hazard models were used to assess the impact of variables on CSS. We performed a pairwise comparison between the COBRA score levels using a log-rank test corrected by Bonferroni, and developed a simplified COBRA score with three risk categories. To compare models, we assessed concordance indices (C-indices), receiver operating characteristic curves with area under the curve (AUC), calibration plots, and decision curve analysis (DCA). Finally, we compared both COBRA and simplified COBRA models with the established American Joint Committee on Cancer (AJCC) model. RESULTS: A total of 812 patients were included. All COBRA score variables had a significant impact on CSS in a Cox proportional hazard model. However, pairwise comparison of the COBRA subscores could not differentiate significantly between all COBRA score levels. Based on these findings, we developed a simplified COBRA score by introducing three categories within the following COBRA score ranges: low- (0-1) vs intermediate- (2-4) vs high-risk (5-7). A pairwise comparison could discriminate significantly between all COBRA risk categories. When finally comparing COBRA and simplified COBRA models with the AJCC model, AJCC performed better than both. C-indices, AUCs, calibration plots and DCA for AJCC were all better compared with the original and simplified COBRA models. CONCLUSION: We performed an external validation of the COBRA score in a large bi-institutional cohort. We observed that several risk groups had overlapping CSS, demonstrating suboptimal performance of the COBRA score. Therefore, we constructed a simplified model with three COBRA score risk categories. This model resulted in demarcated risk groups with non-overlapping CSS and good predictive accuracy. However, both COBRA score models were outperformed by the AJCC staging system. Therefore, we conclude that the AJCC staging system should remain the current standard for stratifying patients after RC for CSS.

A Trial-Based Cost-Utility Analysis of Metastasis-Directed Therapy for Oligorecurrent Prostate Cancer.

The optimal management of patients with oligorecurrent prostate cancer (PCa) is unknown. There is growing interest in metastasis-directed therapy (MDT) for this population. The objective was to assess cost-utility from a Belgian healthcare payer's perspective of MDT and delayed androgen deprivation therapy (ADT) in comparison with surveillance and delayed ADT, and with immediate ADT. A Markov decision-analytic trial-based model was developed, projecting the results over a 5-year time horizon with one-month cycles. Clinical data were derived from the STOMP trial and literature. Treatment costs were derived from official government documents. Probabilistic sensitivity analyses showed that MDT is cost-effective compared to surveillance (ICER: €8393/quality adjusted life year (QALY)) and immediate ADT (dominant strategy). The ICER is most sensitive to utilities in the different health states and the first month MDT cost. At a willingness-to-pay threshold of €40,000 per QALY, the cost of the first month MDT should not exceed €8136 to be cost-effective compared to surveillance. The Markov-model suggests that MDT for oligorecurrent PCa is potentially cost-effective in comparison with surveillance and delayed ADT, and in comparison with immediate ADT.

Assessment of the Safety of Glucocorticoid Regimens in Combination With Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer: A Randomized, Open-label Phase 2 Study.

IMPORTANCE: Abiraterone acetate is combined with prednisone, 5 mg, twice daily for metastatic castration-resistant prostate cancer (mCRPC) and with prednisone, 5 mg, once daily for newly diagnosed, high-risk, metastatic castration-sensitive prostate cancer. Understanding the physiological effects of these and other regimens is important. OBJECTIVE: To evaluate the safety of abiraterone acetate with 4 glucocorticoid regimens. DESIGN, SETTING, AND PARTICIPANTS: Open-label, randomized clinical trial (1:1:1:1) of 164 men with mCRPC from 22 hospitals in 5 countries who were randomly assigned to 1 of 4 intervention groups between June 2013 and October 2014. Analyses were conducted from August 2017 to June 2018. INTERVENTIONS: Abiraterone acetate, 1000 mg, once daily with prednisone, 5 mg, twice daily (n = 41), 5 mg once daily (n = 41), 2.5 mg twice daily (n = 40), or dexamethasone, 0.5 mg, once daily (n = 42). MAIN OUTCOMES AND MEASURES: Primary end point was no mineralocorticoid excess (grade ≥1 hypokalemia or grade ≥2 hypertension) through 24 weeks (6 cycles) from treatment. RESULTS: Of 164 men (median [range] age, 70 [50-90] years) randomized to receive abiraterone acetate, 1000 mg, daily with prednisone, 5 mg, twice daily, once daily, or 2.5 mg twice daily, or dexamethasone, 0.5 mg, once daily, 24 (70.6%) of 34 patients (95% CI, 53.8%-83.2%), 14 (36.8%) of 38 patients (95% CI, 23.4%-52.7%), 21 (60.0%) of 35 patients (95% CI, 43.6%-74.4%), and 26 (70.3%) of 37 patients (95% CI, 54.2%-82.5%), respectively, had no mineralocorticoid excess. Plasma adrenocorticotrophic hormone and urinary mineralocorticoid metabolites after 8 weeks were higher with prednisone, 2.5 mg, twice daily and 5 mg once daily than with 5 mg twice daily or dexamethasone, 0.5 mg, once daily. The level of urinary glucocorticoid metabolites appeared higher in patients who did not meet the primary end point, regardless of glucocorticoid regimen. Total lean body mass decreased in the prednisone groups and total body fat increased in the prednisone, 5 mg, twice daily and dexamethasone groups. In the dexamethasone group, there was an increase in serum insulin and homeostatic model assessment of insulin resistance, while total bone mineral density decreased. In the prednisone, 5 mg, twice daily, 5 mg once daily, 2.5 mg twice daily, and dexamethasone groups, median radiographic progression-free survival was 18.5, 15.3, 12.8, and 26.6 months, respectively. CONCLUSIONS AND RELEVANCE: Abiraterone acetate with prednisone, 5 mg, twice daily or dexamethasone, 0.5 mg, once daily met the prespecified threshold for the primary end point (95% CI excluded 50% mineralocorticoid excess); abiraterone acetate with prednisone, 5 mg, once daily or 2.5 mg twice daily did not meet the threshold. Abiraterone acetate in combination with dexamethasone appeared to be particularly active but may be associated with adverse metabolic consequences. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01867710.

Open partial nephrectomy for complex tumours and >4 cm: Is it still the gold standard technique in the minimally invasive era?

The objective of this paper is to discuss the role of open partial nephrectomy (OPN) for complex renal tumours and large renal tumours > 4 cm in the minimally invasive era. The current status of OPN, laparoscopic partial nephrectomy (LPN) and robotic PN are reviewed. The literature search is done using the National Library of Medicine database (PubMed). The indication of OPN has been extended to T1b tumours (4-7 cm). PN and radical nephrectomy (RN) provide equivalent oncological outcomes for these tumours. In addition, there is a growing application of OPN for complex tumours (centrally located, hilar, multifocal). Despite the more challenging cohort of patients, there is no increase in the overall morbidity of OPN. In contemporary cohorts there is an increase in overweight patients and a higher incidence of central tumours treated with OPN. LPN has been extended to select patients with larger renal masses (4-7 cm) and centrally located tumours. LPN for tumours > 4 cm was in the early phase associated with increased complication rate and prolonged warm ischemia time (WIT). Complication rates decreased with improvement of surgical technique and expertise. Early experience with robotic PN is promising and perioperative outcomes are at least comparable to LPN. LPN and robotic PN have to compete with the functional and oncological results of OPN. In the era of nephron-sparing surgery (NSS), OPN remains the established standard for the management of T1 renal tumours in centres without advanced laparoscopic expertise. Complex scenarios with centrally located tumours, tumours in a solitary kidney, and multifocal lesions probably are best managed with OPN. LPN is feasible in numerous clinical scenarios in centres with advanced laparoscopic expertise but remains a challenging operation. Long-term studies are needed to further define the role of the robotic approach for PN.

Continent catheterizable vesicostomy in an adult population: success at high costs.

AIMS: To evaluate the long term outcome, to review the complication ratio and to analyze predicting factors of catheterizable continent vesicostomy in an adult population. To deduct a proper patient counseling policy. METHODS: We identified all patients that underwent a continent vesicostomy between 1998 and 2008. We did not consider patients that underwent orthotopic bladder reconstruction. Patient satisfaction, urinary leakage, catheterization problems were assessed by chart review or interview. Type of primary surgery, revisions (number and type), renal function and complications were assessed by chart review. RESULTS: Thirty-four patients underwent continent vesicostomy using an ileal segment (Monti or Spiral-Monti/Casale technique) or the appendix (Mitrofanoff). One patient underwent a detrusor wall flap. Twenty-one out of 35 patients underwent concomitant bladder augmentation and 2/35 patients bladder neck closure. Mean age at the time of the procedure was 44 years (range 21-80 years). Mean follow up is 60 months (range 6-117 months). Six out of 35 patients undergo surgical excision of the conduit because of untreatable problems. One patient has a permanent indwelling catheter. Two patients voided normal after sacral nerve stimulation. Ten out of 35 patients undergo stoma related revisions. Sixteen out of 35 patients undergo no stoma related revisions. Finally 26/35 patients were continent and had an easy catheterizable stoma. CONCLUSIONS: Continent urinary diversion in an adult population is associated with a high complication and revision rate. Although conversion rate to an ileal conduit is appreciable, the majority of patients (26/35) finally achieve full continence and unobstructed access to the bladder.

Comparing results after surgery in patients with clinical unilateral T3a prostate cancer treated with or without neoadjuvant androgen-deprivation therapy.

OBJECTIVE: To compare the results in patients with unilateral cT3 prostate cancer treated with or with no neoadjuvant androgen-deprivation therapy (nADT), as nADT might have benefit in cT2 prostate cancer, but for cT3 tumours its use remains controversial, and it is unclear whether it can prevent or delay progression after surgery. PATIENTS AND METHODS: Between 1987 and 2004, 235 patients were assessed as having unilateral cT3 disease by a digital rectal examination; before surgery, 200 patients were not treated with nADT and 35 were. The Kaplan-Meier method was used to calculate survival rates. RESULTS: With no nADT the biochemical progression-free survival (PFS) was 59.5%, the clinical PFS was 95.9%, the cancer-specific survival (CSS) was 98.7%, and overall survival was 95.9% at 5 years. With nADT, the biochemical PFS was 43.4%, clinical PFS was 77.6%, CSS was 88.7%, and overall survival was 79.8% at 5 years. The positive surgical margin rate with no nADT and with nADT was 33.5% and 57.1%, respectively, and the respective mean cancer volume was 6.6 mL and 4.0 mL. CONCLUSION: nADT can decrease tumour size but does not reduce the positive surgical margin rate, nor improve the survival rate in unilateral cT3a disease. Because of side-effects and treatment costs, we do not advise nADT in patients with unilateral cT3a prostate cancer.