William P. Parker

Identification of Site-specific Recurrence Following Primary Radiation Therapy for Prostate Cancer Using C-11 Choline Positron Emission Tomography/Computed Tomography: A Nomogram for Predicting Extrapelvic Disease

BACKGROUND Management of recurrent prostate cancer (CaP) after radiotherapy (RT) is dependent on accurate localization of the site of recurrent disease. OBJECTIVE To describe the anatomic patterns and clinical features associated with CaP recurrence following RT identified on advanced imaging. DESIGN, SETTING, AND PARTICIPANTS Retrospective review of 184 patients with a rising prostate-specific antigen (PSA) after RT for CaP. INTERVENTION C-11 choline positron emission tomography/computed tomography (CholPET). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Recurrence patterns were classified as pelvic soft tissue only (as a surrogate for potentially salvageable disease) versus any extrapelvic disease, and clinical features were compared between patterns. Multivariable logistic regression was used to generate a predictive nomogram for extrapelvic recurrence. Discrimination was assessed with a c-index. RESULTS AND LIMITATIONS Recurrence site was identified in 161 (87%) patients, with 95 (59%) sites histologically confirmed. Factors associated with the detection of recurrence included the difference between PSA nadir and PSA at CholPET (odds ratio: 1.30, p<0.01) and National Comprehensive Cancer Network high-risk classification (odds ratio: 10.83, p=0.03). One hundred (54.3%) patients recurred in the pelvic soft tissue only, while 61 (33%) had extrapelvic recurrence. Of 21 patients who underwent CholPET prior to meeting the Phoenix criteria of biochemical failure, 15 (71%) had recurrence identified on CholPET with 11 localized to the pelvis. On multivariable analysis, the difference between PSA nadir and PSA at CholPET, time from RT, and National Comprehensive Cancer Network risk group were predictive of recurrence outside of the pelvis, and a nomogram was generated with a c-index of 0.79. CONCLUSIONS CholPET identified the site of recurrence in 87% of patients with a rising PSA after RT; most commonly within the pelvis in potentially salvageable locations. A predictive nomogram was generated, and pending external validation, this may aid in assessing the risk of disease beyond the pelvis. These findings underscore the importance of advanced imaging when considering management strategies for patients with a rising PSA following primary RT. PATIENT SUMMARY We identified anatomic patterns of recurrence in patients with a rising prostate-specific antigen after radiotherapy using C-11 choline positron emission tomography/computed tomography. Most recurrences were localized to the pelvis and we were able to generate a tool to aid in disease localization prior to evaluation with advanced imaging.

Outcomes Following Complete Surgical Metastasectomy for Patients with Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Purpose: The benefit of complete surgical metastasectomy for patients with metastatic renal cell carcinoma remains controversial due to limited outcome data. We performed a systematic review and meta‐analysis to determine whether complete surgical metastasectomy confers a survival benefit compared to incomplete or no metastasectomy for patients with metastatic renal cell carcinoma. Materials and Methods: Ovid Embase®, MEDLINE®, Cochrane and Scopus® databases were searched for studies evaluating complete surgical metastasectomy for metastatic renal cell carcinoma through January 19, 2016. Only comparative studies reporting adjusted hazard ratios (aHRs) for all cause mortality of incomplete surgical metastasectomy vs complete surgical metastasectomy were included in the analysis. Generic inverse variance with random effects models was used to determine the pooled aHR. Risk of bias was assessed with the Newcastle‐Ottawa Scale. Results: Eight published cohort studies with a low or moderate potential for bias were included in the final analysis. The studies reported on a total of 2,267 patients (958 undergoing complete surgical metastasectomy and 1,309 incomplete surgical metastasectomy). Median overall survival ranged between 36.5 and 142 months for those undergoing complete surgical metastasectomy, compared to 8.4 to 27 months for incomplete surgical metastasectomy. Complete surgical metastasectomy was associated with a reduced risk of all cause mortality compared with incomplete surgical metastasectomy (pooled aHR 2.37, 95% CI 2.03–2.87, p <0.001), with low heterogeneity (I2 = 0%). Complete surgical metastasectomy remained independently associated with a reduction in mortality across a priori subgroup and sensitivity analyses, and regardless of whether we adjusted for performance status. Conclusions: Complete surgical metastasectomy for metastatic renal cell carcinoma is associated with improved survival compared with incomplete surgical metastasectomy based on meta‐analysis of observational data. Consideration should be given to performing complete surgical metastasectomy, when technically feasible, in patients with metastatic renal cell carcinoma who are surgical candidates.

Application of the Stage, Size, Grade, and Necrosis (SSIGN) Score for Clear Cell Renal Cell Carcinoma in Contemporary Patients

BACKGROUND The tumor stage, size, grade, and necrosis (SSIGN) score was originally defined using patients treated with radical nephrectomy (RN) between 1970 and 1998 for clear cell renal cell carcinoma (ccRCC), excluding patients treated with partial nephrectomy (PN). OBJECTIVE To characterize the original SSIGN score cohort with longer follow-up and evaluate a contemporary series of patients treated with RN and PN. DESIGN, SETTING, AND PARTICIPANTS Retrospective single-institution review of 3600 consecutive surgically treated ccRCC patients grouped into three cohorts: original RN, contemporary (1999-2010) RN, and contemporary PN. INTERVENTION RN or PN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The association of the SSIGN score with risk of death from RCC was assessed using a Cox proportional hazards regression model, and predictive ability was summarized with a C-index. RESULTS AND LIMITATIONS The SSIGN scores differed significantly between the original RN, contemporary RN, and contemporary PN cohorts (p<0.001), with SSIGN ≥4 in 53.5%, 62.7%, and 4.7%, respectively (p<0.001). The median durations of follow-up for these groups were 20.1, 9.2, and 7.6 yr, respectively. Each increase in the SSIGN score was predictive of death from RCC (hazard ratios [HRs]: 1.41 for original RN, 1.37 for contemporary RN, and 1.70 for contemporary PN; all p<0.001). The C-indexes for these models were 0.82, 0.84, and 0.82 for original RN, contemporary RN, and contemporary PN, respectively. After accounting for an era-specific improvement in survival among RN patients (HR: 0.53 for contemporary vs original RN; p<0.001), the SSIGN score remained predictive of death from RCC (HR: 1.40; p<0.001). CONCLUSIONS The SSIGN score remains a useful prediction tool for patients undergoing RN with 20-yr follow-up. When applied to contemporary RN and PN patients, the score retained strong predictive ability. These results should assist in patient counseling and help guide surveillance for ccRCC patients treated with RN or PN. PATIENT SUMMARY We evaluated the validity of a previously described tool to predict survival following surgery in contemporary patients with kidney cancer. We found that this tool remains valid even when extended to patients significantly different than were initially used to create the tool.

Impact of Postoperative Radiotherapy in Men with Persistently Elevated Prostate-specific Antigen After Radical Prostatectomy for Prostate Cancer: A Long-term Survival Analysis

BACKGROUND Prostate cancer (PCa) patients with prostate-specific antigen (PSA) persistence after radical prostatectomy (RP) are at increased risk of mortality, although the natural history of these men is heterogeneous and the optimal management has not been established. OBJECTIVE To develop a model to predict cancer-specific mortality (CSM) and to test the impact of radiotherapy (RT) on survival in this setting. DESIGN, SETTING, AND PARTICIPANTS We identified 496 patients treated with RP and lymph node dissection at two referral centers between 1994 and 2014 who had PSA persistence, defined as a PSA level between 0.1 and 2 ng/ml at 6-8 wk after RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES A multivariable model predicting CSM was developed. We assessed whether the impact of postoperative PSA levels on survival differed according to baseline CSM risk. The nonparametric curve fitting method was then used to explore the relationship between baseline CSM risk and 10-yr CSM rates according to postoperative RT. RESULTS AND LIMITATIONS Median follow-up for survivors was 110 mo. Overall, 49 patients experienced CSM. The 10-yr CSM-free survival was 88%. Pathologic grade group and pathologic stage were independent predictors of CSM (all p=0.01). The association between CSM-free survival and PSA at 6-8 wk differed by the baseline CSM risk, whereby the effect of increasing PSA was evident only in patients with a CSM risk of ≥10%. Postoperative RT was beneficial when the predicted risk of CSM was ≥30% (p=0.001 by an interaction test). Our study is limited by its retrospective design. CONCLUSIONS Increasing PSA levels should be considered as predictors of mortality exclusively in men with worse pathologic characteristics. Postoperative RT in this setting was associated with a survival benefit in patients with a CSM risk of ≥30%. Conversely, individuals with a CSM risk of <30% should be initially managed expectantly. PATIENT SUMMARY Not all patients with prostate-specific antigen persistence have a poor prognosis. Pathologic characteristics should be used to estimate the risk of cancer-specific mortality in these individuals and to identify patients who could benefit from postoperative radiotherapy.

Characterization of perioperative infection risk among patients undergoing radical cystectomy: Results from the national surgical quality improvement program.

OBJECTIVES To evaluate the incidence, risk factors, and timing of infections following radical cystectomy (RC). METHODS The American College of Surgeons National Surgical Quality Improvement Project database was queried to identify patients undergoing RC for bladder cancer from 2006 to 2013. Characteristics including year of surgery, age, sex body mass index, diabetes, smoking, renal function, steroid usage, preoperative albumin, preoperative hematocrit, perioperative blood transfusion (PBT), and operative time were assessed for association with the risk of infection within 30 days of RC using multivariable logistic regression. RESULTS A total of 3,187 patients who had undergone RC were identified, of whom 766 (24.0%) were diagnosed with a postoperative infection, at a median of 13 days (interquartile ranges 8-19) after RC. Infections included surgical site infection (SSI) (404; 12.7%), sepsis/septic shock (405; 12.7%), and urinary tract infection (UTI) (309; 9.7%). On multivariable analysis, body mass index≥30kg/m2 (odds ratios [OR] = 1.52; P<0.01), receipt of a PBT (OR = 1.27; P<0.01), and operative time≥480 minutes (OR = 1.72; P<0.01) were significantly associated with the risk of infection. When the outcomes of UTI, SSI, and sepsis were analyzed separately, operative time≥480 minutes remained independently associated with increased infection risk in each model (OR = 2.11 for UTI, OR = 1.63 for SSI, and OR = 1.80 for sepsis/septic shock; all P<0.05), whereas PBT was associated with SSI and sepsis/septic shock (OR = 1.33 and OR = 1.29, respectively; both P< 0.05). CONCLUSIONS Approximately 25% of patients undergoing RC experience an infection within 30 days of surgery. Several potentially modifiable risk factors for infection were identified, specifically PBT and prolonged operative time, which may represent opportunities for future care improvement.

Predicting Oncologic Outcomes in Renal Cell Carcinoma After Surgery

BACKGROUND Predicting oncologic outcomes is important for patient counseling, clinical trial design, and biomarker study testing. OBJECTIVE To develop prognostic models for progression-free (PFS) and cancer-specific survival (CSS) in patients with clear cell renal cell carcinoma (ccRCC), papillary RCC (papRCC), and chromophobe RCC (chrRCC). DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort review of the Mayo Clinic Nephrectomy registry from 1980 to 2010, for patients with nonmetastatic ccRCC, papRCC, and chrRCC. INTERVENTION Partial or radical nephrectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS PFS and CSS from date of surgery. Multivariable Cox proportional hazards regression was used to develop parsimonious models based on clinicopathologic features to predict oncologic outcomes and were evaluated with c-indexes. Models were converted into risk scores/groupings and used to predict PFS and CSS rates after accounting for competing risks. RESULTS AND LIMITATIONS A total of 3633 patients were identified, of whom 2726 (75%) had ccRCC, 607 (17%) had papRCC, and 222 (6%) had chrRCC. Models were generated for each histologic subtype and a risk score/grouping was developed for each subtype and outcome (PFS/CSS). For PFS, the c-indexes were 0.83, 0.77, and 0.78 for ccRCC, papRCC, and chrRCC, respectively. For CSS, c-indexes were 0.86 and 0.83 for ccRCC and papRCC. Due to only 22 deaths from RCC, we did not assess a multivariable model for chrRCC. Limitations include the single institution study, lack of external validation, and its retrospective nature. CONCLUSIONS Using a large institutional experience, we generated specific prognostic models for oncologic outcomes in ccRCC, papRCC, and chrRCC that rely on features previously shown-and validated-to be associated with survival. These updated models should inform patient prognosis, biomarker design, and clinical trial enrollment. PATIENT SUMMARY We identified routinely available clinical and pathologic features that can accurately predict progression and death from renal cell carcinoma following surgery. These updated models should inform patient prognosis, biomarker design, and clinical trial enrollment.

Venous thromboembolism after radical cystectomy: Experience with screening ultrasonography

Abstract Objectives: To detect the incidence of immediate postoperative deep vein thrombosis (DVT) using screening lower extremity ultrasonography (US) in patients undergoing radical cystectomy (RC) and to determine the rate of symptomatic pulmonary embolism (PE) after RC and identify risk factors for venous thromboembolic (VTE) events in a RC population. Patients and methods: We performed a retrospective review of prospective data collected on patients who underwent RC between July 2008 and January 2012. These patients underwent screening US at 2/3 days after RC to determine the rate of asymptomatic DVT. A chart review was completed to identify those who had a symptomatic PE. Univariate and multivariable analysis was used to identify risk factors associated with DVT, PE and total VTE events. Results: In all, 221 patients underwent RC and asymptomatic DVT was identified in 21 (9.5%) on screening US. Nine (4.5%) developed symptomatic PE at a median of 9 days, of which no patients had positive lower extremity US postoperatively. Increased length of hospital stay, increased estimated blood loss, and lower body mass index were linked to risk of PE, and only a previous history of DVT was associated with postoperative DVT. Conclusion: Patients who undergo RC are at high-risk for thromboembolic events and multimodal prophylaxis should be administered. Clinicians should be especially vigilant in those who demonstrate factors associated with higher risk for VTE events.

Evaluation of beta-blockers and survival among hypertensive patients with renal cell carcinoma

OBJECTIVES Beta-blocker use is associated with improved survival for multiple nonurologic malignancies. Our objective was to evaluate the association between beta-blocker use and survival among surgically managed hypertensive patients with clear-cell renal cell carcinoma (ccRCC). METHODS Hypertensive patients with ccRCC treated with either radical or partial nephrectomy between 2000 and 2010 were identified from our Nephrectomy Registry. Beta-blocker use within 90 days before surgery was identified. The associations between beta-blocker use and risk of disease progression, death from renal cell carcinoma (RCC), and all-cause mortality were assessed using Cox proportional hazards regression models. RESULTS In total, 913 hypertensive patients were identified who underwent either partial or radical nephrectomy for ccRCC. Of these, 104 (11%) had documented beta-blocker use within 90 days before surgery. At last follow-up (median 8.2y among survivors), 258 patients showed progression (median 1.6y following surgery), and 369 patients had died (median 4.1y following surgery), including 138 who died of RCC. After adjusting for PROG (progression-free survival) and SSIGN (cancer-specific survival) scores, beta-blocker use was not significantly associated with the risk of disease progression (hazard ratio [HR] = 0.94; 95% CI: 0.61-1.47; P = 0.80) or the risk of death from RCC (HR = 0.74; 95% CI: 0.38-1.41; P = 0.35). Similarly, on multivariable analysis adjusting for clinicopathologic features, there was not a significant association between beta-blocker use and the risk of all-cause mortality (HR = 0.83; 95% CI: 0.59-1.16; P = 0.27). CONCLUSIONS Beta-blocker use for hypertension within 90 days before surgery was not associated with the risk of progression, death from RCC, or death from any cause.

Patient factors associated with 30-day complications after partial nephrectomy: A contemporary update

INTRODUCTION Patient-level factors associated with perioperative complications after partial nephrectomy (PN) have not been well described in a contemporary series. METHODS Single-institution retrospective study evaluating patients undergoing open, laparoscopic, and robotic PN between 2001 and 2012. Univariable and multivariable logistic regression models were evaluated to assess factors associated with complications within 30 days of surgery. RESULTS We identified 1,763 patients who underwent 1,773 PNs between 2001 and 2012. From 2001 to 2006, 766 PNs were performed (85% open, 15% laparoscopic, and<1% robotic); in contrast, from 2007 to 2012, 1,007 PNs were performed (75% open, 8% laparoscopic, and 17% robotic); P<0.001. Overall, 241 (14%) PNs resulted in an early surgical complication. Patients undergoing a minimally invasive approach had smaller tumors (P<0.001), were less likely to have a solitary kidney (P<0.001), and had a lower Charlson score (P = 0.004). On multivariable analysis, factors independently associated with an increased risk of any complication included male sex (odds ratio [OR] = 1.40), solitary kidney (OR = 1.71), estimated glomerular filtration rate (OR = 2.89 for estimated glomerular filtration rate<30), Charlson score (OR = 1.97 for Charlson score≥3), and tumor size (OR = 1.12 for each 1-cm increase in tumor size); meanwhile, laparoscopic and robotic approaches were associated with a lower risk for complication (OR = 0.017 and 0.016, respectively), all P< 0.05. CONCLUSION Several patient-level factors are associated with 30-day complications after PN, regardless of surgical approach. These data may inform counseling before PN, including potential identification and selection of high-risk surgical candidates for percutaneous ablative approaches.

Identification of Recurrence Sites Following Post-Prostatectomy Treatment for Prostate Cancer Using 11C-Choline Positron Emission Tomography and Multiparametric Pelvic Magnetic Resonance Imaging

Purpose We describe anatomical sites of recurrence in patients with prostate cancer who had biochemical recurrence following radical prostatectomy and who received radiotherapy and/or androgen deprivation therapy postoperatively. We performed 11C‐choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging. Materials and Methods After radiotherapy and/or androgen deprivation therapy patients who underwent radical prostatectomy were evaluated by 11C‐choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging to determine recurrence patterns and clinicopathological features. Recurrent sites were described as local only (seminal vesicle bed/prostate fossa, vesicourethral anastomosis and bladder neck) or distant metastatic disease. Features associated with the identification of any distant metastatic disease were evaluated by multivariable logistic regression. Results A total of 550 patients were identified. Treatment included androgen deprivation therapy in 108, radiotherapy in 201, and androgen deprivation therapy and radiotherapy in 241. Median prostate specific antigen at evaluation was 3.9, 3.6 and 2.8 ng/ml in patients treated with androgen deprivation therapy, radiotherapy and a combination, respectively. Recurrence developed locally in 77 patients (14%), as distant metastasis only in 411 (75%), and as local and distant metastatic disease in 62 (11%). On multivariable analysis treatment with radiotherapy (OR 7.18, 95% CI 2.92–17.65), and radiotherapy and hormonal therapy (OR 9.23, 95% CI 3.90–21.87, all p <0.01) was associated with increased odds of distant failure at evaluation. Conclusions The combination of 11C‐choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging successfully identified patterns of recurrence after postoperative radiotherapy and/or androgen deprivation therapy at a median prostate specific antigen of less than 4 ng/ml. Half of this cohort had local only recurrence and/or a low disease burden limited to pelvic lymph nodes. These patients may benefit from additional local therapy. These data and this analysis may facilitate the evaluation of such patients with biochemically recurrent prostate cancer.