Gender-specific Differences in Clinicopathologic Outcomes Following Radical Cystectomy: An International Multi-institutional Study of More Than 8000 Patients

Background

The impact of gender on the staging and prognosis of urothelial carcinoma of the bladder (UCB) is insufficiently understood.

Objective

To assess gender-specific differences in pathologic factors and survival of UCB patients treated with radical cystectomy (RC).

Design, setting, and participants

Data from 8102 patients treated with RC (6497 men [80%] and 1605 women [20%]) for UCB between 1971 and 2012 were analyzed.

Outcome measurements and statistical analysis

Multivariable competing-risk regression analyses were performed to evaluate the relationship of gender on disease recurrence (DR) and cancer-specific mortality (CSM). We also tested the interaction of gender and tumor stage, nodal status, and lymphovascular invasion (LVI).

Results and limitations

Female patients were older at the time of RC (p = 0.033) and had higher rates of pathologic stage T3/T4 disease (p < 0.001). In univariable, but not in multivariable analysis, female gender was associated with a higher risk of DR (p = 0.022 and p = 0.11, respectively). Female gender was an independent predictor for CSM (p = 0.004). We did not find a significant interaction between gender and stage, nodal metastasis, or LVI (all p values >0.05).

Conclusions

We found female gender to be associated with a higher risk of CSM following RC. However, these findings do not appear to be explained by gender differences in pathologic stage, nodal status, or LVI. This gender disparity may be due to differences in care and/or the biology of UCB.     

Intensity of care in cancer patients in the last year of life: a retrospective data linkage study

Background Delivering high-quality palliative and end-of-life care for cancer patients poses major challenges for health services. We examine the intensity of cancer care in England in the last year of life.Methods We included cancer decedents aged 65+ who died between January 1, 2010 and December 31, 2017. We analysed healthcare utilisation and costs in the last 12 months of life including hospital-based activities and primary care.Results Healthcare utilisation and costs increased sharply in the last month of life. Hospital costs were the largest cost elements and decreased with age (0.78, 95% CI: 0.73–0.72, p < 0.005 for age group 90+ compared to age 65–69 and increased substantially with comorbidity burden (2.2, 95% CI: 2.09–2.26, p < 0.005 for those with 7+ comorbidities compared to those with 1–3 comorbidities). The costs were highest for haematological cancers (1.45, 95% CI: 1.38–1.52, p < 0.005) and those living in the London region (1.10, 95% CI: 1.02–1.19, p < 0.005).Conclusions Healthcare in the last year of life for advanced cancer patients is costly and offers unclear value to patients and the healthcare system. Further research is needed to understand distinct cancer populations’ pathways and experiences before recommendations can be made about the most appropriate models of care.Subject terms: Cancer, Cancer     

Advances in urinary proteome analysis and biomarker discovery

Noninvasive diagnosis of kidney diseases and assessment of the prognosis are still challenges in clinical nephrology. Definition of biomarkers on the basis of proteome analysis, especially of the urine, has advanced recently and may provide new tools to solve those challenges. This article highlights the most promising technological approaches toward deciphering the human proteome and applications of the knowledge in clinical nephrology, with emphasis on the urinary proteome. The data in the current literature indicate that although a thorough investigation of the entire urinary proteome is still a distant goal, clinical applications are already available. Progress in the analysis of human proteome in health and disease will depend more on the standardization of data and availability of suitable bioinformatics and software solutions than on new technological advances. It is predicted that proteomics will play an important role in clinical nephrology in the very near future and that this progress will require interactive dialogue and collaboration between clinicians and analytical specialists.     

Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL)

The best strategy for incorporating imatinib in front-line treatment of Ph+ acute lymphoblastic leukemia (ALL) has not been established. We enrolled 92 patients with newly diagnosed Ph+ ALL in a prospective, multicenter study to investigate sequentially 2 treatment schedules with imatinib administered concurrent to or alternating with a uniform induction and consolidation regimen. Coadministration of imatinib and induction cycle 2 (INDII) resulted in a complete remission (CR) rate of 95% and polymerase chain reaction (PCR) negativity for BCR-ABL in 52% of patients, compared with 19% in patients in the alternating treatment cohort (P = .01). Remarkably, patients with and without a CR after induction cycle 1 (INDI) had similar hematologic and molecular responses after concurrent imatinib and INDII. In the concurrent cohort, grades III and IV cytopenias and transient hepatotoxicity necessitated interruption of induction in 87% and 53% of patients, respectively; however, duration of induction was not prolonged when compared with patients receiving chemotherapy alone. No imatinib-related severe hematologic or nonhematologic toxicities were noted with the alternating schedule. In each cohort, 77% of patients underwent allogeneic stem cell transplantation (SCT) in first CR (CR1). Both schedules of imatinib have acceptable toxicity and facilitate SCT in CR1 in the majority of patients, but concurrent administration of imatinib and chemotherapy has greater antileukemic efficacy.     

Optimization of conditioning for marrow transplantation from unrelated donors for patients with aplastic anemia after failure of immunosuppressive therapy

In 87 patients with aplastic anemia who failed to respond to immunosuppressive treatment, we determined the minimal dose of total body irradiation (TBI) required when added to antithymocyte globulin (ATG, 30 mg/kg x 3) plus cyclophosphamide (CY, 50 mg/kg x 4) to achieve engraftment of unrelated donor marrow. TBI was started at 3 x 200 cGy, to be escalated or deescalated in steps of 200 cGy depending on graft failure or toxicity. Patients were aged 1.3 to 53.5 years (median, 18.6 years). The interval from diagnosis to transplantation was 3 to 328 months (median, 14.6 months). Donors were HLA-A, -B, -C, -DR, and -DQ identical for 62 patients, and nonidentical for 1 to 3 HLA loci at the antigen or allele level for 25. The dose-limiting toxicity was diffuse pulmonary injury. The optimum TBI dose was 1 x 200 cGy. Nine patients did not tolerate ATG and were prepared with CY + TBI. Graft failure occurred in 5% of patients. With a median follow-up of 7 years, 38 (61%) of 62 HLA-identical, and 10 (40%) of 25 HLA-nonidentical transplant recipients are surviving. The highest survival rate with HLA-identical transplants was observed at 200 cGy TBI. Thus, low-dose TBI + CY + ATG conditioning resulted in excellent outcome of unrelated transplants in patients with aplastic anemia who had received multiple transfusions.