Bishoy A. Gayed

A paradigm for the treatment of prostate cancer bone metastases based on an understanding of tumor cell–microenvironment interactions

The pliability of cancer cells to mutate into several different phenotypes in an attempt to find one that will survive and colonize at the metastatic site is a tremendous “hurdle” to overcome in designing novel cancer therapeutics. New targets of therapy are essential if we are to effectively overcome the evasiveness of cancer. The interaction between the tumor cell and the surrounding microenvironment creates a vicious cycle that perpetuates disease survival and progression. The future of cancer therapy resides in the ability to focus on the recruited and exploited relationships of the cancer cell with the host environment. These therapies target cancer cell growth early and interrupt the vicious cycle that is created by the tumor cells interacting with bone components by inhibiting osteoclasts, osteoblasts, stromal cells, and endothelial cells. They alter the bone microenvironment, creating a hostile “soil” that prevents the “seed” from developing into bone metastases and represent a potential new platform for the development of prostate cancer therapeutics.

Prospective Analysis of Ki-67 as an Independent Predictor of Oncologic Outcomes in Patients with High Grade Upper Tract Urothelial Carcinoma

PURPOSE We determined the association of the proliferation marker Ki-67 with pathological parameters and oncologic outcomes in patients with high grade upper tract urothelial carcinoma. MATERIALS AND METHODS Immunohistochemical staining for Ki-67 was done prospectively in 101 consecutive patients undergoing radical nephroureterectomy/ureterectomy for high grade upper tract urothelial carcinoma. Data were compared based on Ki-67 status (normal vs over expressed). Survival was assessed by the Kaplan-Meier method. Cox regression analysis was done to identify independent predictors of time dependent outcomes. RESULTS Median patient age was 70.0 years and median followup was 22.0 months (range 1 to 77). Overall, 30.2% of the population experienced recurrence and 24.8% died of upper tract urothelial carcinoma. Organ confined disease (T2 or less and lymph node negative), lymphovascular invasion and sessile architecture were present in 56.3%, 33.3% and 20.8% of patients, respectively. Ki-67 was over expressed in 73.3% of patients and associated with adverse pathological features. Patients with over expressed Ki-67 had significantly worse recurrence-free survival (43.2 vs 69.0 months, p = 0.006) and cancer specific survival (48.9 vs 68.9 months, p = 0.031) than patients with normal Ki-67. Patients with nonmetastatic disease similarly had worse recurrence-free survival (40.7 vs 71.8 months, p = 0.003) and cancer specific survival (41 months vs not attained, p = 0.008) for over expressed vs normal Ki-67. After adjusting for the effects of organ vs nonorgan confined disease Ki-67 over expression was an independent predictor of recurrence-free survival in the total cohort (HR 4.3, p = 0.05) and in patients with nonmetastatic disease (HR 8.5, p = 0.038). CONCLUSIONS Ki-67 over expression was associated with adverse pathological features in cases of upper tract urothelial carcinoma. It was also an independent predictor of recurrence-free survival in patients with high grade upper tract urothelial carcinoma.

Degree of hydronephrosis predicts adverse pathological features and worse oncologic outcomes in patients with high-grade urothelial carcinoma of the upper urinary tract

OBJECTIVE To evaluate degree of hydronephrosis (HN) as a surrogate for adverse pathological features and oncologic outcomes in patients with high-grade (HG) and low-grade (LG) upper tract urothelial carcinomas (UTUCs). METHODS We retrospectively reviewed 141 patients with localized UTUCs that underwent extirpative surgery at a tertiary referral center. Preoperative imaging was used to evaluate presence and degree of ipsilateral HN. We evaluated degree of HN (none/mild vs. moderate/severe), pathological findings, and oncologic outcomes. RESULTS HG UTUC was present in 113 (80%) patients, muscle-invasive disease (≥pT2) in 49 (35%), and non-organ-confined disease (≥pT3) in 41 (29%). At a median follow-up of 34 months, 49 (35%) patients experienced intravesical recurrence, 28 (20%) developed local/systemic recurrence, and 24 (17%) died of UTUC. HN was graded as none/mild in 77 (55%) patients and moderate/severe in 64 (45%). In patients with HG UTUC, but not LG, degree of HN was associated with advanced pathological stage (P<0.001), positive lymph nodes (P = 0.01), local/systemic recurrence-free survival (hazard ratio [HR] = 5.5, P = 0.02), and cancer-specific survival (HR = 5.2, P = 0.02). On multivariable analysis of preoperative factors, degree of HN in patients with HG UTUC was associated with muscle invasion (HR = 9.3; 95% CI: 3.08-28.32; P<0.001), non-organ-confined disease (HR = 4.5; 95% CI: 1.66-12.06; P = 0.003), local/systemic recurrence-free survival (HR = 2.5; 95% CI: 1.07-5.64; P = 0.04), and cancer-specific survival (HR = 2.6; 95% CI: 1.05-6.22; P = 0.04). CONCLUSIONS Degree of HN can serve as a surrogate for advanced disease and predict worse oncologic outcomes in HG UTUC. Degree of HN was not predictive of intravesical or local/systemic recurrence in LG UTUC.

Obesity Adversely Affects Health Related Quality of Life Before and After Radical Retropubic Prostatectomy

PURPOSE Obesity adversely affects surgical procedures and outcomes. We used a validated health related quality of life measure to examine the effects of obesity on disease specific health related quality of life before and following radical retropubic prostatectomy. MATERIALS AND METHODS From June 2000 to April 2003, 575 consecutive patients with prostate cancer were approached to participate in a prospective, health related quality of life study. Health related quality of life was assessed before surgery, and 1, 4, 12, 24 and 36 months postoperatively. Repeated measures mixed models were constructed to determine the independent effects of body mass index on health related quality of life. RESULTS Of 472 consenting subjects 376 (80%) completed a baseline and at least 1 followup survey. Higher body mass index was associated with worse preoperative hormonal/vitality function (p = 0.0009) and bother (p = 0.02), and delayed recovery of bowel function (p = 0.01) and bother (p = 0.01) health related quality of life. There were no measurable differences postoperatively in hormonal/vitality, urinary or sexual health related quality of life associated with higher body mass index. Increased body mass index was associated with prostate specific antigen recurrence (p = 0.05) and adjuvant treatment (p = 0.02). Adjuvant treatment was independently associated with worse bowel function (p = 0.01) and bother (p = 0.01) health related quality of life in obese patients. At 24 months bowel health related quality of life in obese patients no longer significantly differed from that in nonobese patients. CONCLUSIONS Obesity is associated with worse preoperative hormonal/vitality health related quality of life, slower recovery of bowel function and bother health related quality of life after radical retropubic prostatectomy, and prostate specific antigen recurrence. Impaired health related quality of life recovery in obese patients is influenced by disease recurrence and resultant adjuvant therapies. Despite these findings obese patients should not be dissuaded from considering prostatectomy as definitive treatment for localized prostate cancer.

Ki67 is an independent predictor of oncological outcomes in patients with localized clear‐cell renal cell carcinoma

To validate the impact of Ki67 expression on oncological outcomes of patients treated for clinically localized clear‐cell renal cell carcinoma (ccRCC).

Comparative Analysis of Oncologic Outcomes of Partial Ureterectomy vs Radical Nephroureterectomy in Upper Tract Urothelial Carcinoma

OBJECTIVE To compare oncologic outcomes in an international cohort of patients who underwent either partial ureterectomy (PU) or radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS A subgroup of patients from the UTUC Collaboration with operation classified as PU or RNU was used (n = 835). Clinicopathologic outcomes were evaluated. Survival was assessed using the Kaplan-Meier method. Cox regression addressed recurrence-free survival (RFS) and cancer-specific survival (CSS). RESULTS Median age and follow-up were 69 years (range 32-97 years) and 34 months (range 1-246 months), respectively. Relapse occurred in 28.5% of patients (19.6% local, 8.9% systemic). At analysis, 180 patients (21.6%) died of UTUC. Eighty-one patients (9.7%) underwent PU and 754 (90.3%) underwent RNU. High tumor grade (77.3% vs 55.6%, P <.001) and advanced T stage (>T1, 41.7% vs 30.9%, P <.001) were significantly more common in the RNU cohort. Significantly more patients in the PU group received adjuvant chemotherapy than the RNU arm (25.9% vs 16.8%, respectively, P = .05). Kaplan-Meier median 5-year survival probabilities for RFS (69.4% vs 75.9%, P = .06) and CSS (67.5% vs 72.1%, P = .06) were not significantly different between PU and RNU. On multivariable analysis, Eastern Cooperative Oncology Group (ECOG) performance status, tumor stage, tumor necrosis, and lymph node (LN) status were significantly associated with CSS. CONCLUSION In patients with UTUC, PU seems to provide oncologic efficacy equal to RNU. Ability to maximize global renal function with utilization of PU is an attractive strategy in carefully selected patients.

Cost-Effectiveness of Fluorescence In Situ Hybridization in Patients with Atypical Cytology for the Detection of Urothelial Carcinoma

PURPOSE Patients with atypical cytology and equivocal or negative cystoscopy pose a challenge due to uncertainty about the presence of cancer. We determined the cost-effectiveness of using fluorescence in situ hybridization assays to determine the need for biopsy in patients with atypical cytology and equivocal or negative cystoscopy. MATERIALS AND METHODS Data from 2 large prospective studies evaluating the usefulness of fluorescence in situ hybridization in the setting of atypical cytology to detect urothelial carcinoma were combined. The data were used to calculate sensitivity and specificity for the UroVysion fluorescence in situ hybridization assay in various clinical scenarios. Cost data were obtained from our institution and Medicare reimbursement rates. Evaluations with or without bladder biopsy and with or without upper tract evaluation were considered. RESULTS The study included 263 patients with atypical cytology and equivocal (62) or negative (201) cystoscopy. In patients with equivocal cystoscopy (assuming biopsy was performed in the operating room) biopsy based on fluorescence in situ hybridization results saved

Prospective comparison of molecular signatures in urothelial cancer of the bladder and the upper urinary tract - Is there evidence for discordant biology?

1,740 per patient (

Prognostic role of cell cycle and proliferative biomarkers in patients with clear cell renal cell carcinoma.

3,267 vs

Surgical management of the distal ureter during radical nephroureterectomy is an independent predictor of oncological outcomes: results of a current series and a review of the literature.

1,527 per patient) and avoided 42 biopsies compared to biopsy in all patients. If office based biopsies were used then cost savings using fluorescence in situ hybridization results were