Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. PATIENTS AND METHODS: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. RESULTS: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the 'CIS' versus 'no-CIS' groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63-1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01-1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23-2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34-0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82-1.35; p = 0.70). CONCLUSION: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.

Nomogram Predicting Bladder Cancer-specific Mortality After Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-invasive Bladder Cancer: Results of an International Consortium.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) is associated with improved overall and cancer-specific survival. The post-NAC pathological stage has previously been reported to be a major determinant of outcome. OBJECTIVE: To develop a postoperative nomogram for survival based on pathological and clinical parameters from an international consortium. DESIGN, SETTING, AND PARTICIPANTS: Between 2000 and 2015, 1866 patients with MIBC were treated at 19 institutions in the USA, Canada, and Europe. Analysis was limited to 640 patients with adequate follow-up who had received three or more cycles of NAC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A nomogram for bladder cancer-specific mortality (BCSM) was developed by multivariable Cox regression analysis. Decision curve analysis was used to assess the model's clinical utility. RESULTS AND LIMITATIONS: A total of 640 patients were identified. Downstaging to non-MIBC (ypT1, ypTa, and ypTis) occurred in 271 patients (42 %), and 113 (17 %) achieved a complete response (ypT0N0). The 5-yr BCSM was 47.2 % (95 % confidence interval [CI]: 41.2-52.6 %). On multivariable analysis, covariates with a statistically significant association with BCSM were lymph node metastasis (hazard ratio [HR] 1.90 [95% CI: 1.4-2.6]; p < 0.001), positive surgical margins (HR 2.01 [95 % CI: 1.3-2.9]; p < 0.001), and pathological stage (with ypT0/Tis/Ta/T1 as reference: ypT2 [HR 2.77 {95 % CI: 1.7-4.6}; p < 0.001] and ypT3-4 [HR 5.9 {95 % CI: 3.8-9.3}; p < 0.001]). The area under the curve of the model predicting 5-yr BCSM after cross validation with 300 bootstraps was 75.4 % (95 % CI: 68.1-82.6 %). Decision curve analyses showed a modest net benefit for the use of the BCSM nomogram in the current cohort compared with the use of American Joint Committee on Cancer staging alone. Limitations include the retrospective study design and the lack of central pathology. CONCLUSIONS: We have developed and internally validated a nomogram predicting BCSM after NAC and radical cystectomy for MIBC. The nomogram will be useful for patient counseling and in the identification of patients at high risk for BCSM suitable for enrollment in clinical trials of adjuvant therapy. PATIENT SUMMARY: In this report, we looked at the outcomes of patients with muscle-invasive bladder cancer in a large multi-institutional population. We found that we can accurately predict death after radical surgical treatment in patients treated with chemotherapy before surgery. We conclude that the pathological report provides key factors for determining survival probability.

Surgical management of noninvasive bladder cancer (stages Ta/T1/CIS).

Transurethral removal of bladder cancer is performed for diagnostic and therapeutic reasons. Tissue is returned for histologic determination of tumor grade and stage. For tumors that do not invade the detrusor muscle, resection can be curative although there is a high rate of new tumor occurrence. Surgical removal not only eradicates visible existing lesions but also retrieves material for histologic evaluation. This examination allows a determination of tumor grade as well as stage. Because of the importance of good histologic information in determining prognosis and, possibly, the need for further therapy, the method of surgical removal is important.

Right ureteral injury after radiofrequency ablation for atrial fibrillation.

Percutaneous radiofrequency ablation is a common procedure to treat atrial fibrillation. We describe a patient without a urologic history who had immediate abdominal pain after this treatment. Computed tomography scan and cystoscopy/retrograde pyelography confirmed a right proximal ureteral injury with urinary extravasation. The patient was treated with right ureteral stent placement and urethral catheter drainage. This case appears to be the first report of percutaneous radiofrequency ablation complicated by spontaneous ureteral injury related to blunt injury during manipulation of the transseptal sheaths or intracardiac catheters.

Radical prostatectomy and collaborative care pathways.

The purpose of this study was to describe the development, implementation, and evaluation of a collaborative care pathway for radical retropubic prostatectomy. The experience of Vanderbilt University Medical Center is described, and the literature was reviewed. In addition, an example of the radical prostatectomy care pathway is provided for an illustration of a care path. The experience of using collaborative care pathways at Vanderbilt Medical Center has resulted in decreased length of stays, decreased blood utilization, and decreased overall costs. Also, staff satisfaction has improved all without compromising patient care. Collaborative care pathways have been shown to be a cost effective way of standardizing patient care without sacrificing the quality of patient care. In addition, they allow for an easier way to critically evaluate outcomes, costs, and patient and staff satisfaction.

Effects of spinal cord transection and MK-801 on CGRP immunostaining in the rat urinary bladder.

Numerous studies have demonstrated that lesions in the CNS can alter the density of sensory nerve processes in peripheral organs. In the present study, rat spinal cords were transected at the second lumbar segmental level and the density of calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers in the urinary bladder was examined. Additional rats had spinal cord transections followed by 12 days of treatment with the N-methyl-D-aspartate receptor antagonist, MK-801. In the bladders of control rats, CGRP-immunoreactive fibers were present as thick nerve trunks, perivascular plexi, and a fine meshwork of varicose nerve fibers. Twelve days following a spinal cord transection, the density of CGRP-immunoreactive nerve fibers was markedly reduced; occasional fibers appeared primarily as nonvaricose fine fibers. In bladders from rats receiving a spinal cord transection and MK-801 treatment, CGRP-immunoreactive fibers were abundantly distributed throughout the detrusor muscle; these fibers exhibited numerous varicosities as well as some enlarged terminal varicosities. These data demonstrate that (i) an upper motor neuron-type lesion markedly decreases the density of CGRP-immunoreactive peripheral afferent nerve processes and (ii) following a spinal cord transection, MK-801 appears to enhance the density of CGRP immunostaining in the bladder.

CGRP-immunoreactive primary afferent nerve fibers in the rat urinary bladder: effects of dorsal rhizotomy and MK-801.

A transection lesion of the suprasacral spinal cord results in a decreased density of calcitonin gene-related peptide (CGRP)-immunoreactive (I) primary afferent nerve fibers in the rat urinary bladder. The fiber density can be restored by postsurgical treatment with the N-methyl-D-aspartate receptor antagonist MK-801. We are attempting to determine the level of the primary afferent neuron at which MK-801 might have a restorative effect on CGRP immunostaining. Thus, the purpose of this study was to determine if MK-801 had a similar restorative effect on immunostaining for CGRP in bladder nerves after a direct lesion of the sacral afferent system, i.e., rhizotomy of the L6 and S1 dorsal roots. To assess the effect of the lesion, the mean length and number of bladder CGRP-I nerve fibers, as well as the number of CGRP-I perikarya in the L6 and S1 dorsal root ganglia (DRG), were measured following bilateral L6 and S1 dorsal rhizotomies. Both the mean length and the numbers of CGRP-I bladder fibers were significantly decreased by the lesion. However, the number of CGRP-I primary afferent perikarya in the L6 and S1 DRG was unchanged from control values. Rats which received rhizotomies and subsequent treatment with MK-801 did not exhibit restoration of the density of CGRP-I bladder fibers nor an alteration in the number of CGRP-I primary afferent perikarya. These data suggest that MK-801-induced restoration of bladder CGRP-I primary afferent nerve fibers may rely on an intact central process.