Michael Froehner

Complications Following Radical Cystectomy for Bladder Cancer in the Elderly

CONTEXT The incidence of bladder cancer increases with advancing age. Considering the increasing life expectancy and the increasing proportion of elderly people in the general population, radical cystectomy will be considered for a growing number of elderly patients who suffer from muscle-invasive or recurrent bladder cancer. OBJECTIVE This article reviews contemporary complication and mortality rates after radical cystectomy in elderly patients and the relationship between age and short-term outcome after this procedure. EVIDENCE ACQUISITION A literature review was performed using the PubMed database with combinations of the following keywords cystectomy, elderly, complications, and comorbidity. English-language articles published in the year 2000 or later were reviewed. Papers were included in this review if the authors investigated any relationship between age and complication rates with radical cystectomy for bladder cancer or if they reported complication rates stratified by age groups. EVIDENCE SYNTHESIS Perioperative morbidity and mortality are increased and continence rates after orthotopic urinary diversion are impaired in elderly patients undergoing radical cystectomy. Complications are frequent in this population, particularly when an extended postoperative period (90 d instead of 30 d) is considered. CONCLUSIONS Although age alone does not preclude radical cystectomy for muscle-invasive or recurrent bladder cancer or for certain types of urinary diversion, careful surveillance is required, even after the first 30 d after surgery. Excellent perioperative management may contribute to the prevention of morbidity and mortality of radical cystectomy, supplementary to the skills of the surgeon, and is probably a reason for the better perioperative results obtained in high-volume centers.

Defining a standard set of patient-centered outcomes for men with localized prostate cancer.

BACKGROUND Value-based health care has been proposed as a unifying force to drive improved outcomes and cost containment. OBJECTIVE To develop a standard set of multidimensional patient-centered health outcomes for tracking, comparing, and improving localized prostate cancer (PCa) treatment value. DESIGN, SETTING, AND PARTICIPANTS We convened an international working group of patients, registry experts, urologists, and radiation oncologists to review existing data and practices. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The group defined a recommended standard set representing who should be tracked, what should be measured and at what time points, and what data are necessary to make meaningful comparisons. Using a modified Delphi method over a series of teleconferences, the group reached consensus for the Standard Set. RESULTS AND LIMITATIONS We recommend that the Standard Set apply to men with newly diagnosed localized PCa treated with active surveillance, surgery, radiation, or other methods. The Standard Set includes acute toxicities occurring within 6 mo of treatment as well as patient-reported outcomes tracked regularly out to 10 yr. Patient-reported domains of urinary incontinence and irritation, bowel symptoms, sexual symptoms, and hormonal symptoms are included, and the recommended measurement tool is the Expanded Prostate Cancer Index Composite Short Form. Disease control outcomes include overall, cause-specific, metastasis-free, and biochemical relapse-free survival. Baseline clinical, pathologic, and comorbidity information is included to improve the interpretability of comparisons. CONCLUSIONS We have defined a simple, easily implemented set of outcomes that we believe should be measured in all men with localized PCa as a crucial first step in improving the value of care. PATIENT SUMMARY Measuring, reporting, and comparing identical outcomes across treatments and treatment centers will provide patients and providers with information to make informed treatment decisions. We defined a set of outcomes that we recommend being tracked for every man being treated for localized prostate cancer.

Cisplatin, methotrexate and bleomycin for treating advanced penile carcinoma

To retrospectively evaluate the efficacy and toxicity of chemotherapy with cisplatinum, methotrexate and bleomycin (CMB) in the adjuvant and palliative setting, and its effect on survival in patients with locally advanced or metastatic penile carcinoma, which carries a very poor prognosis.

Comparison of the American Society of Anesthesiologists Physical Status classification with the Charlson score as predictors of survival after radical prostatectomy

OBJECTIVES To compare the American Society of Anesthesiologists Physical Status (ASA) classification with the Charlson score in the radical prostatectomy setting. The ASA classification is a widely accepted way to evaluate perioperative risk. At present, the Charlson score is probably the most frequently used comorbidity measure to predict long-term survival after radical prostatectomy. METHODS A total of 444 consecutive patients were enrolled in this study. The ASA classification was obtained from the anesthesia chart, and the Charlson score was assigned based on conditions noted during the preoperative cardiopulmonary risk assessment or mentioned on the discharge document. Kaplan-Meier time-event curves and Mantel-Haenszel hazard ratios were estimated for comorbid (noncancer) and overall survival. RESULTS After a mean follow-up of 5.9 years, both classifications were able to predict comorbid and overall survival in dose-response patterns. The ASA classification was superior in terms of a clearer discrimination of the survival curves (lower P values, higher hazard ratios). Both classifications identified a high-risk group (ASA 3 and Charlson score 2 or more), but only the ASA classification sufficiently defined a low-risk group (ASA 1). CONCLUSIONS In experienced hands, the ASA classification is a promising tool to improve the classification of prognostic comorbidity in the radical prostatectomy setting and may be used as an alternative to the Charlson score.

Treating renal cell cancer in the elderly

To determine whether age and comorbidity are predictors of peri‐operative complications and/or mortality in surgery for renal cell cancer in a retrospective study of patients aged >75 years.

Incidence, risk profile and morphological pattern of venous thromboembolism after prostate cancer surgery

Summary.  Background: Venous thromboembolism (VTE) is the most common non‐surgical complication after major pelvic surgery. Little is known about the risk factors or the time of development of postoperative venous thrombosis. Methods: A cohort of 523 consecutive patients undergoing radical prostatectomy with lymphadenectomy was prospectively assessed by complete compression ultrasound at days −1, +8 and +21. Results: Complete data were available in 415 patients, while four patients had VTE before surgery and were excluded from the analysis. In the remaining 411 patients, 71 VTE events were found in 69 patients (16.8%). Most were limited to calf muscle veins (56.5%), followed by deep calf vein thrombosis (23.2%), proximal deep vein thrombosis (DVT, 14.5%) and pulmonary embolism (PE, 5.8%). Of the 14 patients with proximal DVT/PE, 11 patients (78.6%) developed VTE between days 8 and 21. Risk factors for VTE were a personal history of VTE (OR 3.0), pelvic lymphoceles (LCs) impairing venous flow (OR 2.8) and necessity of more than two units of red blood cells (OR 2.6). Conclusion: Venous thromboembolism is common after radical prostatectomy. A significant proportion develops after day 8, suggesting that prolonged heparin prophylaxis should be considered. Since LCs with venous flow reduction result in higher rates of VTE, hemodynamically relevant lymphoceles should be surgically treated.

Comparison of systematic transrectal biopsy to transperineal magnetic resonance imaging/ultrasound-fusion biopsy for the diagnosis of prostate cancer

To compare targeted, transperineal magnetic resonance imaging (MRI)/ultrasound (US)‐fusion biopsy to systematic transrectal biopsy in patients with previous negative or first prostate biopsy and to evaluate the gain in diagnostic information with systematic biopsies in addition to targeted MRI/US‐fusion biopsies.

Perioperative Complications after Radical Prostatectomy: Open versus Robot-Assisted Laparoscopic Approach

Background: The best technique of radical prostatectomy - open versus robot-assisted approach - is controversially discussed. In this study, we compared the complication rates of open and robot-assisted radical prostatectomy during the introduction and subsequent routine use of a da Vinci® robotic device while open surgery remained the standard approach. Patients and Methods: Between January 1st, 2006, and June 4th, 2012, 2,754 men underwent radical prostatectomy at our department. Among them, 317 received robot-assisted and 2,438 open surgery. According to the requirements for prostate cancer centers certified by the Deutsche Krebsgesellschaft (German Cancer Society), a prospective database recording perioperative complications was built up. The complication rates of open and robot-assisted radical prostatectomy were compared with the χ2 or Fisher exact test. The distributions of quantitative variables were compared with U tests. Results: Whereas the demographic factors favored patients selected for robot-assisted radical prostatectomy, there were no differences between open and robot-assisted surgery concerning length of stay, autologous blood transfusion rates and the incidence of perioperative complications. Conclusions: Open and robot-assisted radical prostatectomy had comparable complication rates. With better patient- and tumor-related parameters as well as decreasing transfusion rates in the robot-assisted subgroup, this observation might reflect the learning curves of the involved robotic surgeons.

Analyses of potential predictive markers and survival data for a response to sunitinib in patients with metastatic renal cell carcinoma.

Background Patients with metastatic clear cell renal cell carcinoma (ccRCC) are frequently treated with tyrosine kinase inhibitors (TKI) such as sunitinib. It inhibits angiogenic pathways by mainly targeting the receptors of VEGF and PDGF. In ccRCC, angiogenesis is characterized by the inactivation of the von Hippel-Lindau gene (VHL) which in turn leads to the induction of HIF1α target genes such as CA9 and VEGF. Furthermore, the angiogenic phenotype of ccRCC is also reflected by endothelial markers (CD31, CD34) or other tumor-promoting factors like Ki67 or survivin. Methods Tissue microarrays from primary tumor specimens of 42 patients with metastatic ccRCC under sunitinib therapy were immunohistochemically stained for selected markers related to angiogenesis. The prognostic and predictive potential of theses markers was assessed on the basis of the objective response rate which was evaluated according to the RECIST criteria after 3, 6, 9 months and after last report (12–54 months) of sunitinib treatment. Additionally, VHL copy number and mutation analyses were performed on DNA from cryo-preserved tumor tissues of 20 ccRCC patients. Results Immunostaining of HIF-1α, CA9, Ki67, CD31, pVEGFR1, VEGFR1 and -2, pPDGFRα and -β was significantly associated with the sunitinib response after 6 and 9 months as well as last report under therapy. Furthermore, HIF-1α, CA9, CD34, VEGFR1 and -3 and PDGRFα showed significant associations with progression-free survival (PFS) and overall survival (OS). In multivariate Cox proportional hazards regression analyses high CA9 membrane staining and a response after 9 months were independent prognostic factors for longer OS. Frequently observed copy number loss and mutation of VHL gene lead to altered expression of VHL, HIF-1α, CA9, and VEGF. Conclusions Immunoexpression of HIF-1α, CA9, Ki67, CD31, pVEGFR1, VEGFR1 and -2, pPDGFRα and -β in the primary tumors of metastatic ccRCC patients might support the prediction of a good response to sunitinib treatment.

A review of studies of hormonal adjuvant therapy in prostate cancer.

There is increasing interest in the use of adjuvant hormonal therapies, which are given after the resection or destruction of all gross disease, in early-stage prostate cancer, as a significant proportion of patients experience progression and/or die from the disease despite undergoing therapy with curative intent. Several retrospective studies suggest that adjuvant hormonal therapy may improve long-term outcome after radical surgery in men with positive lymph nodes, although this approach has yet to be studied in a prospective setting. No studies of adjuvant therapy for patients with extracapsular extension at surgery have been completed, but in an interim analysis of an open controlled trial, adjuvant flutamide significantly improved progression-free survival at 4 years. Three prospective studies in the radiotherapy setting have shown that adjuvant luteinizing hormone-releasing hormone (LH-RH) agonist therapy significantly improves progression-free and/or overall survival. Future studies need to define patient subgroups who will benefit most from adjuvant therapy. The side effects of the different therapeutic options also need to be compared. It is hoped that many of the outstanding questions concerning adjuvant hormonal therapy will be answered by the ongoing Bicalutamide Early Prostate Cancer Programme.