David A. Green

Intensity of 18Fluorodeoxyglucose Uptake in Positron Emission Tomography Distinguishes Between Indolent and Aggressive Non-Hodgkin’s Lymphoma

PURPOSE (18)Fluorodeoxyglucose positron emission tomography (FDG PET) is widely used for the staging of lymphoma. We investigated whether the intensity of tumor FDG uptake could differentiate between indolent and aggressive disease. MATERIALS AND METHODS PET studies of 97 patients with non-Hodgkins lymphoma who were untreated or had relapsed and/or persistent disease and had not received treatment within the last 6 months were analyzed, and the highest standardized uptake value (SUV) per study was recorded. Correlations were made with histopathology. RESULTS FDG uptake was lower in indolent than in aggressive lymphoma for patients with new (SUV, 7.0 +/- 3.1 v 19.6 +/- 9.3; P < .01) and relapsed (SUV, 6.3 +/- 2.7 v 18.1 +/- 10.9; P = .04) disease. Despite overlap between indolent and aggressive disease in the low SUV range (indolent, 2.3 to 13.0; aggressive, 3.2 to 43.0), all cases of indolent lymphoma had an SUV <or= 13. A receiver operating characteristic (ROC) analysis demonstrated that the SUV distinguished reasonably well between aggressive and indolent disease (area under ROC curve, 84.7%), and an SUV > 10 excluded indolent lymphoma with a specificity of 81%. With a higher cutoff for the SUV, the specificity would have been higher. CONCLUSION FDG uptake is lower in indolent than in aggressive lymphoma. Patients with NHL and SUV > 10 have a high likelihood for aggressive disease. This information may be helpful if there is discordance between biopsy and clinical behavior.

Urothelial carcinoma of the bladder and the upper tract: disparate twins.

PURPOSE Urothelial carcinoma of the bladder is the 4th most common malignancy in men and the 8th most common cause of male cancer death in the United States. Conversely, upper tract urothelial carcinoma accounts for only 5% to 10% of all urothelial carcinoma. Due to the relative preponderance of urothelial carcinoma of the bladder, much of the clinical decision making regarding upper tract urothelial carcinoma is extrapolated from evidence that is based on urothelial carcinoma of the bladder cohorts. In fact, only 1 major urological organization has treatment guidelines specific for upper tract urothelial carcinoma. While significant similarities exist between these 2 diseases, ignoring the important differences may be preventing us from optimizing therapy in patients with upper tract urothelial carcinoma. Therefore, we explored these dissimilarities, including the differential importance of gender, anatomy, staging, intracavitary therapy, surgical lymphadenectomy and perioperative systemic chemotherapy on the behavior of urothelial carcinoma of the bladder and upper tract urothelial carcinoma. MATERIALS AND METHODS A nonsystematic literature search using the MEDLINE/PubMed® database was conducted to identify original articles, review articles and editorials. Searches were limited to the English language and studies in humans and in adults, and used the key words urothelial carcinoma, upper tract urothelial carcinoma or transitional cell carcinoma combined with several different sets of key words to identify appropriate publications for each section of the manuscript. The key words, broken down by section, were 1) epidemiology, sex, gender; 2) location, tumor location; 3) staging, stage; 4) intracavitary, intravesical, topical therapy; 5) lymphadenectomy, lymph node, lymph node dissection and 6) adjuvant, neoadjuvant, chemotherapy. RESULTS Women who present with urothelial carcinoma of the bladder do so with less favorable tumor characteristics and have worse survival than men. However, gender does not appear to be associated with survival outcomes in upper tract urothelial carcinoma. The prognostic effect that urothelial carcinoma tumor location has on outcomes prediction is a matter of debate, and the influence of tumor location may reflect our technical ability to accurately stage and treat the disease more than the actual tumor biology. Moreover, technical limitations of upper tract urothelial carcinoma sampling compared to transurethral resection for urothelial carcinoma of the bladder are the most important source of staging differences between the 2 diseases. Intravesical chemotherapy and immunotherapy are essential components of standard of care for most nonmuscle invasive bladder cancer, while adjuvant intracavitary therapy for patients with upper tract urothelial carcinoma treated endoscopically or percutaneously has been sparsely used and without any clear guidelines. The widespread adoption of the use of intracavitary therapy in the upper tract will likely not only require additional data to support its efficacy, but will also require a less cumbersome means of administration. Lymphadenectomy at the time of radical cystectomy is widely accepted while lymphadenectomy at the time of radical nephroureterectomy is performed largely at the discretion of the surgeon. Among other reasons, this may be due in part to the variable lymphatic drainage along the course of the ureter compared to the relatively confined lymphatic landing sites for the bladder. Level I evidence has demonstrated a clear survival benefit for systemic chemotherapy before radical surgery or radiation in patients with clinical T2-4N0M0 urothelial carcinoma of the bladder. Such data are not available in the population with upper tract urothelial carcinoma. However, the use of neoadjuvant chemotherapy may be even more important in upper tract urothelial carcinoma than in urothelial carcinoma of the bladder because of the obligatory kidney function loss that occurs at radical nephroureterectomy. CONCLUSIONS While urothelial carcinoma of the bladder and upper tract urothelial carcinoma share many characteristics, they represent 2 distinct diseases. There are practical, anatomical, biological and molecular differences that warrant consideration when risk stratifying and treating patients with these disparate twin diseases. To overcome the challenges that impede progress toward evidence-based medicine in upper tract urothelial carcinoma, we believe that focused collaborative efforts will best augment our understanding of this rare disease and ultimately improve the care we deliver to our patients.

Impact of histological variants on oncological outcomes of patients with urothelial carcinoma of the bladder treated with radical cystectomy

OBJECTIVE To investigate the impact of variant histologies of urothelial carcinoma of the bladder (UCB) on oncologic outcomes after radical cystectomy (RC). MATERIALS AND METHODS Data from 1984 UCB patients treated by RC without preoperative chemo- or radiotherapy were reviewed for histological differentiation and variants. We analysed the differences between pure UCB and UCB with variant histology, and those between the different histological variants using various stratifications. RESULTS Overall, 488 (24.6%) patients had UCB variants with squamous cell (11.4%) and glandular differentiation (3.8%) being the most common. Histological UCB variants were associated with advanced tumour stage, lymphovascular invasion and lymph node metastasis (all p-values<0.01) when compared to pure UCB. In univariable analyses, patients with non-squamous UCB variants were at significantly higher risk for disease recurrence and cancer-specific mortality than those with pure UCB patients (p-values=0.001) and those with squamous cell differentiated UCB (p-values=0.04); the latter two had the same risk. In multivariable analyses that adjusted for the effects of standard clinicopathologic characteristics, variant UCB histology was not associated with both survival end-points. In patients treated with adjuvant chemotherapy (n=492) there was no difference in cancer-specific survival between pure UCB, squamous cell differentiated UCB and other histological UCB variants. CONCLUSIONS A quarter of UCB patients treated with RC harboured histological UCB variants. Variant UCB histologies were associated with features of biologically aggressive disease. While variant UCB histology was associated with worse outcomes in univariable analyses, this effect did not remain significant in multivariable analyses.

Impact of Histological Variants on Clinical Outcomes of Patients with Upper Urinary Tract Urothelial Carcinoma

PURPOSE We investigated the clinical and prognostic impact of variant histologies on upper tract urothelial carcinoma outcomes after radical nephroureterectomy. MATERIALS AND METHODS Data on 1,648 patients with upper tract urothelial carcinoma treated with radical nephroureterectomy without preoperative chemotherapy or radiotherapy were reviewed for histological differentiation and variants. We analyzed differences between pure upper tract urothelial carcinoma and upper tract urothelial carcinoma with variant histology, and differences in the histological variants using different stratifications. RESULTS A total of 398 patients (24.2%) had histological upper tract urothelial carcinoma variants. The most common variants were squamous cell and glandular differentiation in 9.9% and 4.4% of cases, respectively. Histological variants were associated with advanced tumor stage, tumor multifocality, sessile tumor architecture, tumor necrosis, lymphovascular invasion and lymph node metastasis compared to pure upper tract urothelial carcinoma (p ≤0.031). On univariable analysis variant histology was associated with disease recurrence (p = 0.002) and cancer specific mortality (p = 0.003). In 174 patients treated with adjuvant chemotherapy there was no difference in disease recurrence or survival between variant histology and pure upper tract urothelial carcinoma (p = 0.42 and 0.59, respectively). On multivariable analysis adjusted for the effects of standard clinicopathological characteristics variant histology was not associated with either end point. CONCLUSIONS Almost 25% of patients with upper tract urothelial carcinoma treated with radical nephroureterectomy harbored histological variants. Variant histology was associated with features of biologically aggressive upper tract urothelial carcinoma. While variant histology is associated with worse outcomes on univariable analysis but this effect did not remain significant on multivariable analysis.

Predictors of cancer-specific mortality after disease recurrence following radical cystectomy.

Study Type – Therapy (case series)

A prospective pilot study of 89Zr-J591/prostate specific membrane antigen positron emission tomography in men with localized prostate cancer undergoing radical prostatectomy

PURPOSE In this pilot study we explored the feasibility of (89)Zr labeled J591 monoclonal antibody positron emission tomography of localized prostate cancer. MATERIALS AND METHODS Before scheduled radical prostatectomy 11 patients were injected intravenously with (89)Zr-J591, followed 6 days later by whole body positron emission tomography. Patients underwent surgery the day after imaging. Specimens were imaged by ex vivo micro positron emission tomography and a custom 3 Tesla magnetic resonance scanner coil. Positron emission tomography images and histopathology were correlated. RESULTS Median patient age was 61 years (range 47 to 68), median prostate specific antigen was 5.2 ng/ml (range 3.5 to 12.0) and median biopsy Gleason score of the 11 index lesions was 7 (range 7 to 9). On histopathology 22 lesions were identified. Median lesion size was 5.5 mm (range 2 to 21) and median Gleason score after radical prostatectomy was 7 (range 6 to 9). Eight of 11 index lesions (72.7%) were identified by in vivo positron emission tomography. Lesion identification improved with increasing lesion size for in vivo and ex vivo positron emission tomography (each p <0.0001), and increasing Gleason score (p = 0.14 and 0.01, respectively). Standardized uptake values appeared to correlate with increased Gleason score but not significantly (p = 0.19). CONCLUSIONS To our knowledge this is the first report of (89)Zr-J591/prostate specific membrane antigen positron emission tomography in localized prostate cancer cases. In this setting (89)Zr-J591 bound to tumor foci in situ and positron emission tomography identified primarily Gleason score 7 or greater and larger tumors, likely corresponding to clinically significant disease warranting definitive therapy. A future, larger clinical validation trial is planned to better define the usefulness of (89)Zr-J591 positron emission tomography for localized prostate cancer.

Accurate preoperative prediction of non-organ-confined bladder urothelial carcinoma at cystectomy

Upstaging to non‐organ‐confined (NOC) disease is frequent at the time of radical cystectomy for urothelial carcinoma of the bladder (UCB). Pre‐surgical models that can accurately predict which patients are likely to have more extensive disease are sparse. The present study developed an accurate nomogram for the prediction of NOC‐UCB based on a cohort of patients with clinically organ‐confined disease. Adoption of such a tool into daily clinical decision‐making may lead to more appropriate integration of perioperative chemotherapy, thereby potentially improving survival in patients with UCB.

Role of magnetic resonance imaging in bladder cancer: current status and emerging techniques

Whats known on the subject? and What does the study add?

Robotic-assisted Radical Cystectomy With Extracorporeal Urinary Diversion for Urothelial Carcinoma of the Bladder: Analysis of Complications and Oncologic Outcomes in 175 Patients With a Median Follow-up of 3 Years

OBJECTIVE To report oncologic outcomes and complications after robotic-assisted radical cystectomy (RARC). MATERIALS AND METHODS From March 2004 to August 2011, 175 consecutive patients underwent RARC with extracorporeal urinary diversion at our institution by a single surgeon. The study design was prospective. Perioperative parameters and postoperative complications were prospectively collected using the modified Clavien system. Recurrence-free survival and cancer-specific survival curves were generated using the Kaplan-Meier method. RESULTS A total of 145 men and 30 women with a median age of 73 years and a median body mass index of 27 kg/m(2) underwent RARC. Four patients (2.3%) required conversion to open surgery because of difficulty to progress. One hundred nine patients (62%) underwent a transcutaneous ileal conduit, 40 patients (23%) an orthotopic neobladder, and 26 (15%) a continent cutaneous conduit. The median operating time was 360 minutes (interquartile range [IQR]: 300-420). The median estimated blood loss was 400 mL (IQR: 250-612), with a transfusion rate of 17.0%. The median postoperative length of stay was 7.0 days (IQR: 5.2-10). Early (<30 days) and late surgery-related complications (30-90 days) occurred in 74 (42%) and 59 (34%) patients, respectively. The perioperative mortality rate was 2.8%. The positive soft tissue surgical margins rate was 5%. The median number of lymph nodes removed was 19 (IQR: 12-28). The median follow-up was 37 months (IQR: 21.5-53.5). Actuarial recurrence-free survival and cancer-specific survival at 2, 3, and 5 years after RARC were 67%, 63%, 63% and 73%, 68%, 66%, respectively. CONCLUSION RARC achieved mid-term oncologic efficacy. Moreover, the complication rates were comparable with open radical cystectomy series.

Outcomes and prognostic factors in patients with a single lymph node metastasis at time of radical cystectomy

Lymph node (LN) metastasis is a critical predictor for disease recurrence and cancer‐specific survival in patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy. Patients with a low LN disease burden (pN1) might be cured by surgery alone, while patients with a high LN disease burden (stage ≥ pN2) might benefit most from adjuvant chemotherapy. We found that outcomes of patients with pN1 UCB are significantly affected by pathological stage and soft tissue surgical margin status. Our nomogram may help to improve outcomes prediction in patients with pN1 UCB. An accurate prediction of the individual risk of outcomes may help risk stratifying patients with pN1 UCB to help improve clinical decision‐making.