Delayed Intervention of Small Renal Masses on Active Surveillance

Although surgical excision is the standard of therapy for small renal masses (SRMs), there is a growing recognition of active surveillance as an option in select patients who are poor surgical candidates or who have shorter life expectancy. A number of patients on expectant management, however, subsequently advance to definitive therapy. In this study, we systematically reviewed the literature and performed a pooled analysis of active surveillance series to evaluate the rate and indications for definitive treatment after initiating a period of active surveillance. Fourteen clinical series (1245 patients; 1364 lesions) met our selection criteria. Mean lesion size at presentation was 2.30 ± 0.40 cm with a mean follow-up of 33.6 ± 16.9 months. Collectively, 34.0% of patients underwent delayed intervention, which ranged in individual series from 3.6% to 70.3%. Of patients undergoing delayed intervention, the average time on active surveillance prior to definitive treatment was 27.8 ± 10.6 months. A pooled analysis revealed that 41.0% of patients underwent therapy secondary to tumor growth rate and 51.9% secondary to patient or physician preference in the absence of clinical progression. Overall, 1.1% of all patients progressed to metastatic disease during the average follow-up period. Thus, active surveillance may be an appropriate option for carefully selected patients with SRMs. However, delayed treatment is pursued in a significant percentage of patients within 3 years. Prospective registries and clinical trials with standardized indications for delayed intervention are needed to establish true rates of disease progressions and recommendations for delayed intervention

Predictive Nomogram for Recurrence following Surgery for Nonmetastatic Renal Cell Cancer with Tumor Thrombus

Purpose Following surgery for nonmetastatic renal cell carcinoma with tumor thrombus the risk of recurrence is significant but variable among patients. The purpose of this study was to develop and validate a predictive nomogram for individual estimation of recurrence risk following surgery for renal cell carcinoma with venous tumor thrombus. Materials and Methods Comprehensive data were collected on patients with nonmetastatic renal cell carcinoma and thrombus treated at a total of 5 institutions from 2000 to 2013. Independent predictors of recurrent renal cell carcinoma from a competing risks analysis were developed into a nomogram. Predictive accuracy was compared between the development and validation cohorts, and between the nomogram and the UISS (UCLA Integrated Staging System, SSIGN (Stage, Size, Grade and Necrosis) and Sorbellini models. Results A total of 636 patients were analyzed, including the development cohort of 465 and the validation cohort of 171. Independent predictors, including tumor diameter, body mass index, preoperative hemoglobin less than the lower limit of normal, thrombus level, perinephric fat invasion and nonclear cell histology, were developed into a nomogram. Estimated 5-year recurrence-free survival was 49% overall. Five-year recurrence-free survival in patients with 0, 1, 2 and more than 2 risk factors was 77%, 53%, 47% and 20%, respectively. Predictive accuracy was similar in the development and validation cohorts (AUC 0.726 and 0.724, respectively). Predictive accuracy of the thrombus nomogram was higher than that of the UISS (AUC 0.726 vs 0.595, p = 0.001), SSIGN (AUC 0.713 vs 0.612, p = 0.04) and Sorbellini models (AUC 0.709 vs 0.638, p = 0.02). Conclusions We present a predictive nomogram for postoperative recurrence in patients with nonmetastatic renal cell carcinoma with venous thrombus. Improving individual postoperative risk assessment may allow for better design and analysis of future adjuvant clinical trials

Treatment trends of muscle invasive bladder cancer: Evidence from the Surveillance, Epidemiology, and End Results database, 1988 to 2013

Objective: Guidelines for muscle-invasive bladder cancer (MIBC) recommend that patients receive neoadjuvant chemotherapy with radical cystectomy as treatment over radical cystectomy alone. Though trends and practice patterns of MIBC have been defined using the National Cancer Database, data using the Surveillance, Epidemiology, and End Results (SEER) program have been poorly described. Methods: Using the SEER database, we collected data of MIBC according to the American Joint Commission on Cancer. We considered differences in patient demographics and tumor characteristics based on three treatment groups: chemotherapy (both adjuvant and neoadjuvant) with radical cystectomy, radical cystectomy, and chemoradiotherapy. Multinomial logistic regression was performed to compare likelihood ratios. Temporal trends were included for each treatment group. Kaplan-Meier curves were performed to compare cause-specific survival. A Cox proportional-hazards model was utilized to describe predictors of survival. Results: Of 16 728 patients, 10 468 patients received radical cystectomy alone, 3236 received chemotherapy with radical cystectomy, and 3024 received chemoradiotherapy. Patients who received chemoradiotherapy over radical cystectomy were older and more likely to be African American; stage III patients tended to be divorced. Patients who received chemotherapy with radical cystectomy tended to be males; stage II patients were less likely to be Asian than Caucasian. Stage III patients were less likely to receive chemoradiotherapy as a treatment option than stage II. Chemotherapy with radical cystectomy and chemoradiotherapy are both underutilized treatment options, though increasingly utilized. Kaplan-Meier survival curves showed significant differences between stage II and III tumors at each interval. A Cox proportional-hazards model showed differences in gender, tumor stage, treatment modality, age, and marital status. Conclusion: Radical cystectomy alone is still the most commonly used treatment for muscle-invasive bladder cancer based on temporal trends. Significant disparities exist in those who receive radical cystectomy over chemoradiotherapy for treatment

Clinicopathologic Data at Diagnosis.

<p>Clinicopathologic Data at Diagnosis.</p

Higher GLB1 levels after neoadjuvant ADT in prostate cancer tumor tissues.

<p>Immunohistochemistry for GLB1 was performed on tissue arrays as described in the methods and staining quantitated automatically using VECTRA. Lower power H&E staining (20X) of control (A) and neoadjuvant (B) ADT treated intermediate grade prostate cancer tissues. Morphologic changes associated with ADT exposure include shrinkage/loss of acini (→) making Gleason scoring inapplicable. Increased levels of GLB1 (purple) are shown in nuclear and cytoplasmic compartments of ADT treated (D) and untreated (C) epithelium under higher power. (E) Epithelial (tumor) levels of GLB1 were significantly increased in ADT treated specimens overall and in the cytoplasm. (F) No significant increases in GLB1 expression in stromal tissue treated with ADT compared to untreated tissues. *p<0.05; mean±SE.</p

GLB1 levels increase after ADT in intermediate grade PCa and over time.

<p>(A) GLB1 expression was measured in radical prostatectomy specimens categorized by ADT status and pretreatment Gleason grade. Higher levels of GLB1 were expressed in intermediate PCa tissues treated with ADT. GLB1 after ADT was not increased in high grade cancers (Gleason 8 + 9). (B) GLB1 expression was evaluated over neoadjuvant ADT treatment duration. PCa tissues exposed to ADT longer than 5 months expressed significantly higher levels of GLB1 compared to no ADT, but shorter durations of ADT exposure did not reach significance. (*p<0.05;**p<0.01; mean±SE).</p

Cleaved caspase 3 (CC3) expression increases in intermediate grade cancers and occurs early after ADT.

<p>CC3 immunohistochemistry was performed on neoadjuvant ADT and control prostate tissues and then quantitated using the automated imaging analyzer VECTRA. Gleason scoring was performed on pretreatment biopsies. (A) Cell nuclear and cytoplasmic levels of CC3 demonstrate increased expression in ADT treated PCa tissues and increased levels in Gleason score 6 and 7 (B) compared to untreated controls. (C) CC3 expression is shown according to duration of neoadjuvant ADT treatment and compared to untreated controls. Significant increases in CC3 levels were seen within 1-5mo after ADT initiation. *p<0.05; mean±SE.</p