Purpose of review

With the pervasive use of prostate-specific antigen-based screening, many men in the US are now diagnosed with prostate cancer in their 50s or earlier. However, the majority of tumors are still detected among men over 65-years-old. The appropriate management of localized disease among these older men is controversial.

Recent findings

The US Preventive Services Task Force recently strengthened its recommendation against screening men over 75 years old. To date, however, screening among older patients remains common, and does not adequately reflect patient life expectancy. Older men are more likely to be diagnosed with higher-risk tumors, but are less likely to receive curative local therapy, and are more likely to be managed with primary androgen deprivation therapy. Careful active surveillance is an increasingly viable option for selected older men with low-risk tumors; focal therapy and low-intensity medical therapy may be emerging alternatives in the near future.

Summary

Decisions regarding both screening and treatment should consider patient comorbidity, life expectancy, and treatment preferences rather than chronologic age. Treatment also must be tailored to the level of tumor risk. Increased use of active surveillance, together with diet and lifestyle intervention, is appropriate for many older men with lower-risk tumors. Conversely, those with high-risk disease should not be denied the opportunity for curative local therapy on the basis of age alone.

Purpose

Higher hospital and clinician volumes may be associated with improved patient outcomes for complex surgical and medical care, although the strength and consistency of this association varies markedly across specific conditions and procedures. Pressures from payors and policymakers exist to move complex care to high volume hospitals. The net effect of these pressures may be the regionalization of care. We quantified trends in the regionalization of inpatient care for urological oncology in a national administrative database.

Materials and methods

The Nationwide Inpatient Sample, a 20% stratified sample of United States community hospital admissions, was queried for surgical and nonsurgical admissions for bladder, renal and prostate cancer care between 1988 and 2002. Hospitals were grouped into tertiles by annual surgical volume. Trends over time in the annual discharge rate by hospital volume tertile, geographic region and insurance status were analyzed.

Results

High volume hospitals were defined by at least 22, 12 and 26 cases per year for bladder, renal and prostate cancer, respectively. High volume hospital discharges increased significantly as a proportion of all discharges for bladder (67% to 70%) and renal (67% to 73%) cancer surgery, and they were essentially constant for prostate surgery (76%). Trends were similar for Medicare and Medicaid patients except high volume hospital discharges for prostate cancer decreased during the study period. Significant regional variation was observed for the regionalization of surgical and nonsurgical care.

Conclusions

Nationwide Inpatient Sample data demonstrate the ongoing regionalization of urological oncology care. The policy implications of this trend are complex with potentially important benefits and risks in terms of access to and quality of care.

The surgical management of clinically localized bladder cancer is challenging, and the quality of care delivered to patients with bladder cancer is a subject of increasing interest. Multiple large studies have examined the association between surgical volume and outcomes after radical cystectomy. These studies generally find lower mortality and complication rates at high-volume centers, though interpretation of the data must be tempered by limitations of the datasets driving the studies. Benefits of regionalization of care also must be weighed against other measures proven to predict outcomes; a delay in time to cystectomy beyond 3 months, for example, is strongly associated with increased mortality. Other candidate process measures supported by existing literature include adequacy of lymphadenectomy as measured by nodal yield and availability or offering of orthotopic diversion when appropriate. Assessment and reporting of bladder cancer outcomes should be risk adjusted based on oncologic risk factors and patient comorbid illness. Perioperative morbidity and mortality, cause-specific survival, and overall survival are all key measures. Assessment of health-related quality of life after bladder cancer treatment should also be standardized for reporting. Multiple survey instruments have been developed in recent years, but none has yet been well validated or widely adopted. In particular, capturing variation in quality of life outcomes between patients undergoing bladder-sparing protocols vs. continent diversion vs. incontinent diversion is an important but difficult goal that has not yet been met. The urologic oncology community should take a strong lead in achieving consensus regarding the definition, assessment, and reporting of quality of care data for bladder cancer.

Objective

Apart from cystectomy, few treatment options exist for the management of bacillus Calmette-Guerin refractory non-muscle invasive bladder cancer (NMIBC). We report a multi-institutional experience with sequential intravesical combination chemotherapy using gemcitabine and mitomycin C (MMC) for NMIBC in the treatment of high-risk patients.

Methods

We performed a retrospective review of patients who received 6 weekly treatments with sequential intravesical gemcitabine (1g) and MMC (40 mg) chemotherapy for NMIBC. Gemcitabine was administered first and retained for 90 minutes and then drained. MMC was then administered directly after and retained for an additional 90 minutes. Forty-seven patients received treatment from 3 academic tertiary referral centers between 2000 and 2010.

Results

Forty-seven patients (median age 70, range 32-85; 36 males, 11 females) who previously failed a median of 2 intravesical treatments were reviewed. Complete response, 1-year, and 2-year recurrence-free survival rates for all patients were 68%, 48%, and 38%, respectively. Median recurrence-free survival for all patients was 9 months (range 1-80). Fourteen of 47 patients (30%) remained free of recurrence with a median time to follow-up of 26 months (range 6-80 mo). Ten patients required cystectomy.

Conclusion

Sequential intravesical combination chemotherapy using gemcitabine and MMC appears to be a useful treatment for patients with high-grade NMIBC as well as those with prior bacillus Calmette-Guerin failure. Further prospective studies are warranted.

Unlabelled

We have developed an in vivo method to quantify antibody uptake using (111)In-capromab pendetide SPECT combined with CT (SPECT/CT). Our goal was to evaluate this method for potential grading of prostate tumors.

Methods

Our phantom experiments focused on the robustness of an advanced iterative reconstruction algorithm that involves corrections for photon attenuation, scatter, and geometric blurring caused by radionuclide collimators. The conversion factors between image values and tracer concentrations (in Bq/mL) were calculated from a uniform phantom filled with an aqueous solution of (111)InCl(3) using the same acquisition protocol and reconstruction parameters as for patient studies. In addition, the spatial resolution of the reconstructed images was measured from a point source phantom. The measured spatial resolution was modeled into a point-spread function, and the point-spread function was implemented in a deconvolution-based partial-volume-error correction algorithm. The recovery capability to correctly estimate true tracer concentrations was tested using prostatelike and bladderlike lesion phantoms fitted in the modified National Electrical Manufacturers Association/International Electrotechnical Commission body phantom. Patients with biopsy-proven prostate cancer (n = 10) who underwent prostatectomy were prospectively enrolled in the preoperative SPECT/CT studies at the San Francisco Veterans Affairs Medical Center. The CT portion of SPECT/CT was used to generate CT-based attenuation maps and as an anatomic localization tool for clinical interpretation. Pathologic Gleason grades were compared with in vivo antibody uptake value (AUV) normalized by injected dose, effective half-life, and injection-scan time difference. AUVs were calculated in each lobe of the prostate gland with cylindric volumes of interest having dimensions of 1.5 cm in both diameter and height.

Results

Reconstructed SPECT images further corrected by the deconvolution-based partial-volume-error correction could recover tracer concentrations up to 90% of true values in measurements of phantom volumes as small as 7.77 mL. From patient studies, there was a statistically significant correlation (rho = 0.71, P = 0.033) between higher AUVs (from either left or right lobe) and higher components of pathologic Gleason scores.

Conclusion

Our results strongly indicate potential for noninvasive prostate tumor grading using quantitative (111)In-capromab pendetide SPECT/CT.

Introduction

Although randomized controlled trials (RCTs) remain the gold standard for determining evidence-based clinical practices, large disease registries that enroll large numbers of patients have become paramount as a relatively cost-effective additional tool.

Methods

We highlight the advantages of disease registries focusing on the example of prostate cancer and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE™) registry.

Results

CaPSURE collects approximately 1,000 clinical and patient-reported variables, in over 13,000 men that are enrolled. Thus far, CaPSURE has yielded over 130 peer-reviewed publications, with several others in press, in key areas of risk migration, practice patterns, outcome prediction, and quality of life outcomes.

Conclusions

Disease registries, like CaPSURE complement RCTs and CaPSURE, have provided a means to better understand many aspects of prostate cancer epidemiology, practice patterns, oncologic and HRQOL outcomes, and costs of care across populations. Specialized observational disease registries such as CaPSURE provide insight and have broad implications for disease management and policy.

Objectives

Currently, there are few options other than cystectomy for the management of BCG refractory non-muscle invasive bladder cancer. We report our experience with intravesical combination chemotherapy using gemcitabine and MMC in such patients.

Materials and methods

We identified all patients with non-muscle invasive bladder cancer who were BCG refractory or intolerant and had been treated with intravesical gemcitabine and MMC at our institution. Patients were treated with a combination of intravesical gemcitabine (1000 mg in 50 ml sterile water) followed sequentially by intravesical MMC (40 mg in 20 ml sterile water) every week for 6 weeks (induction). Induction therapy was followed by a maintenance regimen using the same dose of gemcitabine and MMC once a month for 12 months. Data regarding patient demographics and disease information such as previous intravesical therapy, previous cystoscopy, cytology results, time to recurrence, and side effect profile were collected.

Results

A total of 10 patients (6 male and 4 female) aged 48 to 85 years (median 67 years) underwent treatment with a median follow-up of 26.5 months (4-34 months). Six patients were recurrence free and have maintained their response at a median of 14 months (4-34 months). Four patients had biopsy proven recurrence. Median time to recurrence was 6 months (range 4-13 months). The therapy was well tolerated in all patients. There were no major complications. Two patients experienced irritative lower urinary tract symptoms, which did not require cessation of therapy and one experienced a maculopapillary rash that improved with benadryl.

Conclusions

In patients with recurrent BCG refractory bladder cancer, intravesical combination chemotherapy with gemcitabine and MMC appears to be well tolerated and yields a response in a good proportion number of patients.

[This corrects the article DOI: 10.1371/journal.pone.0089754.].