Matthew Kent

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

Study Type – Therapy (case series)

Gender-specific differences in clinicopathologic outcomes following radical cystectomy: An international multi-institutional study of more than 8000 patients

BACKGROUND The impact of gender on the staging and prognosis of urothelial carcinoma of the bladder (UCB) is insufficiently understood. OBJECTIVE To assess gender-specific differences in pathologic factors and survival of UCB patients treated with radical cystectomy (RC). DESIGN, SETTING, AND PARTICIPANTS Data from 8102 patients treated with RC (6497 men [80%] and 1605 women [20%]) for UCB between 1971 and 2012 were analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Multivariable competing-risk regression analyses were performed to evaluate the relationship of gender on disease recurrence (DR) and cancer-specific mortality (CSM). We also tested the interaction of gender and tumor stage, nodal status, and lymphovascular invasion (LVI). RESULTS AND LIMITATIONS Female patients were older at the time of RC (p=0.033) and had higher rates of pathologic stage T3/T4 disease (p<0.001). In univariable, but not in multivariable analysis, female gender was associated with a higher risk of DR (p=0.022 and p=0.11, respectively). Female gender was an independent predictor for CSM (p=0.004). We did not find a significant interaction between gender and stage, nodal metastasis, or LVI (all p values >0.05). CONCLUSIONS We found female gender to be associated with a higher risk of CSM following RC. However, these findings do not appear to be explained by gender differences in pathologic stage, nodal status, or LVI. This gender disparity may be due to differences in care and/or the biology of UCB.

A case-mix-adjusted comparison of early oncological outcomes of open and robotic prostatectomy performed by experienced high volume surgeons

Radical prostatectomy provides local‐regional control of prostate cancer and is the most common treatment for prostate cancer in the United States. Over the past decade there has been a shift in the surgical approach used to treat this disease, moving from open retropubic approach to robot‐assisted laparoscopic prostatectomy. While robotic prostatectomy has been demonstrated to result in less blood loss, fewer transfusions and shorter hospital duration, it has never been demonstrated in a meaningful prospective manner to result in improved or even equivalent oncological outcomes. Prior attempts to address this question have been hampered by methodological issues with study design, differences in case mix, or differences in surgical learning curve between surgeons. In this retrospective study we compared the oncological outcomes of open radical prostatectomy and robotic prostatectomy limiting our analysis to expert surgeons in their respective surgical approaches. Importantly, the patient cohort contained a majority of patients with intermediate‐ and high‐risk features and all surgeons attempted to adhere to strict oncological principles, including performing complete pelvic lymph node dissections in almost all of the patients in the study. The results demonstrate that oncological outcomes show no significant difference with respect to surgical approach, even for patients with higher risk features, and that there is more variation between individual surgeons than between surgical approaches.

Combining smoking information and molecular markers improves prognostication in patients with urothelial carcinoma of the bladder

OBJECTIVES Tissue-based markers improve the accuracy of prediction models in urothelial carcinoma of the bladder (UCB). Current smoking status and cumulative exposure also affect outcomes. To evaluate whether the combination of molecular markers and smoking features further improved the prognostication of patients who underwent radical cystectomy (RC) for UCB. MATERIALS AND METHODS A total of 588 patients underwent RC and bilateral lymphadenectomy for UCB from 1995 to 2005. Immunohistochemistry for p53, p21, pRB, p27, Ki-67, and survivin was performed on tissue microarrays from the RC specimen. Smoking features were routinely assessed at diagnosis. Multivariable Cox regression models assessed time to disease recurrence and cancer-specific mortality. RESULTS Of the 588 patients, 128 were never (22%), 283 former (48%), and 177 current smokers (30%). In total, 227 patients experienced disease recurrence, whereas 190 died of UCB. Smoking status was independently associated with both outcomes (hazard ratio [HR] = 1.48 and 2.62, for former and current vs. never smokers, respectively, P<0.001). All markers were significantly associated with both outcomes (P<0.05) except for survivin. The combination of the 4 cell cycle markers p53, p21, pRB, and p27 increased the discrimination of clinicopathologic model for former and current vs. never smokers with c-indices 0.779 and 0.780, respectively (base model c-indices of 0.741 and 0.740 for former and current vs. never smokers, respectively). The further addition of smoking features and biomarker status improved the discrimination of the model (c-indices of 0.783 and 0.786 for former and current vs. never smokers, respectively). CONCLUSIONS We confirmed that smoking information and tissue markers status improve prognostication of UCB outcomes after RC; the combination of both reaching the highest level of discrimination.

Risk Factors for the Development of Parastomal Hernia after Radical Cystectomy

PURPOSE Parastomal hernia is a frequent complication of stoma formation after radical cystectomy. We determined the prevalence and risk factors for the development of parastomal hernia after radical cystectomy. MATERIALS AND METHODS We conducted a retrospective study of 433 consecutive patients who underwent open radical cystectomy and ileal conduit between 2006 and 2010. Postoperative cross-sectional imaging studies performed for routine oncologic followup (1,736) were evaluated for parastomal hernia, defined as radiographic evidence of protrusion of abdominal contents through the abdominal wall defect created by forming the stoma. Univariable and multivariable Cox regression analyses were used to determine clinical and surgical factors associated with parastomal hernia. RESULTS Complete data were available for 386 patients with radiographic parastomal hernia occurring in 136. The risk of a parastomal hernia developing was 27% (95% CI 22, 33) and 48% (95% CI 42, 55) at 1 and 2 years, respectively. Clinical diagnosis of parastomal hernia was documented in 93 patients and 37 were symptomatic. Of 16 patients with clinical parastomal hernia referred for repair 8 had surgery. On multivariable analysis female gender (HR 2.25; 95% CI 1.58, 3.21; p<0.0001), higher body mass index (HR 1.08 per unit increase; 95% CI 1.05, 1.12; p<0.0001) and lower preoperative albumin (HR 0.43 per gm/dl; 95% CI 0.25, 0.75; p=0.003) were significantly associated with parastomal hernia. CONCLUSIONS The overall risk of radiographic evidence of parastomal hernia approached 50% at 2 years. Female gender, higher body mass index and lower preoperative albumin were most associated with the development of parastomal hernia. Identifying those at greatest risk may allow for prospective surgical maneuvers at the time of initial surgery, such as placement of prophylactic mesh in selected patients, to prevent the occurrence of parastomal hernia.

A Systematic Literature Review of Life Expectancy Prediction Tools for Patients with Localized Prostate Cancer

PURPOSE We aimed to develop a clinical decision support tool for clinicians counseling patients with localized prostate cancer. The tool would provide estimates of patient life expectancy based on age, comorbidities and tumor characteristics. We reviewed the literature to find suitable prediction models. MATERIALS AND METHODS We searched the literature for prediction models for life expectancy. Models were evaluated in terms of whether they provided an estimate of risk, incorporated comorbidities, were clinically feasible and gave plausible estimates. Clinical feasibility was defined in terms of whether the model provided coefficients and could be used in the initial consultation for men across a wide age range without an undue burden of data gathering. RESULTS Models in the literature were characterized by the use of life years rather than a risk of death, questionable approaches to comorbidities, implausible estimates, questionable recommendations and poor clinical feasibility. We found tools that involved applying an unvalidated approach to assessing comorbidities to a clearly erroneous life expectancy table, or requiring that a treatment decision be made before life expectancy could be calculated, or giving highly implausible estimates such as a substantial risk of prostate cancer specific mortality even for a highly comorbid 80-year-old with Gleason 6 disease. CONCLUSIONS We found gross deficiencies in current tools that predict risk of death from other causes. No existing model was suitable for implementation in our clinical decision support system.

Preoperative predictive model of recovery of urinary continence after radical prostatectomy

To build a predictive model of urinary continence recovery after radical prostatectomy (RP) that incorporates magnetic resonance imaging (MRI) parameters and clinical data.

Lymph node dissection during cytoreductive nephrectomy: A retrospective analysis

To assess whether regional lymph node dissection could improve the prognosis of patients with metastatic renal cell carcinoma.

Adult UrologyOncology: Prostate/Testis/Penis/UrethraA Systematic Literature Review of Life Expectancy Prediction Tools for Patients with Localized Prostate Cancer

PURPOSE We aimed to develop a clinical decision support tool for clinicians counseling patients with localized prostate cancer. The tool would provide estimates of patient life expectancy based on age, comorbidities and tumor characteristics. We reviewed the literature to find suitable prediction models. MATERIALS AND METHODS We searched the literature for prediction models for life expectancy. Models were evaluated in terms of whether they provided an estimate of risk, incorporated comorbidities, were clinically feasible and gave plausible estimates. Clinical feasibility was defined in terms of whether the model provided coefficients and could be used in the initial consultation for men across a wide age range without an undue burden of data gathering. RESULTS Models in the literature were characterized by the use of life years rather than a risk of death, questionable approaches to comorbidities, implausible estimates, questionable recommendations and poor clinical feasibility. We found tools that involved applying an unvalidated approach to assessing comorbidities to a clearly erroneous life expectancy table, or requiring that a treatment decision be made before life expectancy could be calculated, or giving highly implausible estimates such as a substantial risk of prostate cancer specific mortality even for a highly comorbid 80-year-old with Gleason 6 disease. CONCLUSIONS We found gross deficiencies in current tools that predict risk of death from other causes. No existing model was suitable for implementation in our clinical decision support system.

Accuracy of post-radiotherapy biopsy before salvage radical prostatectomy

To determine whether post‐radiotherapy (RT) biopsy (PRB) adequately predicts the presence, location, and histological features of cancer in the salvage radical prostatectomy (SRP) specimen. Before salvage treatment, a PRB is required to confirm the presence of locally recurrent or persistent cancer and to determine the extent and location of the prostate cancer.