Matthew K. Tollefson

Long-Term Risk of Clinical Progression After Biochemical Recurrence Following Radical Prostatectomy: The Impact of Time from Surgery to Recurrence

BACKGROUND The natural history of biochemical recurrence (BCR) after radical retropubic prostatectomy (RRP) is variable and does not always translate into systemic progression or prostate cancer (PCa) death. OBJECTIVE To evaluate long-term clinical outcomes of patients with BCR and to determine predictors of disease progression and mortality in these men. DESIGN, SETTING, AND PARTICIPANTS We reviewed our institutional registry of 14 632 patients who underwent RRP between 1990 and 2006 to identify 2426 men with BCR (prostate-specific antigen [PSA] levels ≥ 0.4 ng/ml) who did not receive neoadjuvant or adjuvant therapy. Median follow-up was 11.5 yr after RRP and 6.6 yr after BCR. INTERVENTION RRP. MEASUREMENTS Patients were grouped into quartiles according to time from RRP to BCR. Survival after BCR was estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazard regression models were used to analyze clinicopathologic variables associated with systemic progression and death from PCa. RESULTS AND LIMITATIONS Median systemic progression-free survival (PFS) and cancer-specific survival (CSS) had not been reached after 15 yr of follow-up after BCR. Cancer-specific mortality 10 yr after BCR was 9.9%, 9.3%, 7.8%, and 4.7% for patients who experienced BCR <1.2 yr, 1.2-3.1 yr, 3.1-5.9 yr, and >5.9 yr after RRP, respectively (p=0.10). On multivariate analysis, time from RRP to BCR was not significantly associated with the risk of systemic progression (p=0.50) or cancer-specific mortality (p=0.81). Older patient age, increased pathologic Gleason score, advanced tumor stage, and rapid PSA doubling time (DT) predicted systemic progression and death from PCa. Limitations included retrospective design, varied utilization of salvage therapies, and the inclusion of few patients with positive lymph nodes. CONCLUSIONS Only a minority of men experience systemic progression and death from PCa following BCR. The decision to institute secondary therapies must balance the risk of disease progression with the cost and morbidity of treatment, independent of time from RRP to BCR.

Long-Term Complications of Conduit Urinary Diversion

PURPOSE We evaluated long-term surgical complications and clinical outcomes in a large group of patients treated with conduit urinary diversion. MATERIALS AND METHODS We identified 1,057 patients who underwent radical cystectomy with conduit urinary diversion using ileum or colon at our institution from 1980 to 1998 with complete followup information. Patients were followed for long-term clinical outcomes and analyzed for the incidence of diversion specific complications. RESULTS A total of 844 patients died at a median of 4.1 years (range 0.1 to 28.1) following cystectomy. Median followup of the surviving 213 patients was 15.5 years (range 0.3 to 29.1). There were 643 (60.8%) patients with 1,453 complications directly attributable to the urinary diversion performed with a mean of 2.3 complications per patient. Bowel complications were the most common, occurring in 215 patients (20.3%), followed by renal complications in 213 (20.2%), infectious complications in 174 (16.5%), stomal complications in 163 (15.4%) and urolithiasis in 162 (15.3%). The least common were metabolic abnormalities, which occurred in 135 patients (12.8%), and structural complications, which occurred in 122 (11.5%). Increasing age at cystectomy (HR 1.21, p <0.001), increasing Eastern Cooperative Oncology Group performance status (HR 1.23, p = 0.02) and recent era of surgery (HR 1.68, p <0.001) were significantly associated with a higher incidence of complications. CONCLUSIONS Conduit urinary diversion is associated with a high overall complication rate but a low reoperation rate. Long-term followup of these patients is necessary to closely monitor for potential complications from the urinary diversion that can occur decades later.

Sarcopenia in patients with bladder cancer undergoing radical cystectomy: Impact on cancer‐specific and all‐cause mortality

The authors evaluated sarcopenia as a predictor of cancer‐specific survival (CSS) and overall survival (OS) among patients with urothelial cancer of the bladder undergoing radical cystectomy (RC).

The Impact of Perioperative Blood Transfusion on Cancer Recurrence and Survival Following Radical Cystectomy

BACKGROUND While the receipt of a perioperative blood transfusion (PBT) has been associated with an increased risk of mortality for a number of malignancies, the relationship between PBT and survival following radical cystectomy (RC) for bladder cancer (BCa) has not been well established. OBJECTIVE To evaluate the association of PBT with disease recurrence and mortality following RC. DESIGN, SETTING, AND PARTICIPANTS We identified 2060 patients who underwent RC at the Mayo Clinic between 1980 and 2005. PBT was defined as transfusion of allogenic red blood cells during RC or postoperative hospitalization. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Survival was estimated using the Kaplan-Meier method and was compared with the log-rank test. Cox proportional hazard regression models were used to evaluate the association of PBT with outcome, controlling for clinicopathologic variables. RESULTS AND LIMITATIONS A total of 1279 patients (62%) received PBT. The median number of units transfused was 2 (interquartile range [IQR]: 2-4). Patients receiving PBT were significantly older (median: 69 yr vs 66 yr; p<0.0001), had a worse Eastern Cooperative Oncology Group performance status (p<0.0001), and were more likely to have muscle-invasive tumors (56% vs 49%; p = 0.004). Median postoperative follow-up was 10.9 yr (IQR: 7.9-15.7). Receipt of PBT was associated with significantly worse 5-yr recurrence-free survival (58% vs 64%; p = 0.01), cancer-specific survival (59% vs 72%; p<0.001), and overall survival (45% vs 63%; p<0.001). On multivariate analyses, PBT remained associated with significantly increased risks of postoperative tumor recurrence (hazard ratio [HR]: 1.20; p = 0.04), death from BCa (HR: 1.31; p = 0.003), and all-cause mortality (HR: 1.27; p = 0.0002). Among patients who received PBT, an increasing number of units transfused was independently associated with increased cancer-specific mortality (HR: 1.07; p<0.0001) and all-cause mortality (HR: 1.05; p<0.0001). Limitations include selection bias and lack of standardized transfusion criteria. CONCLUSIONS We found that PBT is associated with significantly increased risks of cancer recurrence and mortality following RC. While external validation is required, continued efforts to reduce the use of blood products in these patients are warranted.

Pretreatment Neutrophil-to-Lymphocyte Ratio Is Associated with Advanced Pathologic Tumor Stage and Increased Cancer-specific Mortality Among Patients with Urothelial Carcinoma of the Bladder Undergoing Radical Cystectomy

BACKGROUND Pretreatment neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been associated with adverse survival in a variety of malignancies. However, the relationship between NLR and oncologic outcomes following radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) has not been well studied. OBJECTIVE To evaluate the association of preoperative NLR with clinicopathologic outcomes following RC. DESIGN, SETTING, AND PARTICIPANTS We identified 899 patients who underwent RC without neoadjuvant therapy at our institution between 1994 and 2005 and who had a pretreatment NLR. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Preoperative NLR (within 90 d prior to RC) was recorded. Recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox proportional hazard and logistic regression models were used to analyze the association of NLR with clinicopathologic outcomes. RESULTS AND LIMITATIONS Median postoperative follow-up was 10.9 yr (interquartile range: 8.3-13.9 yr). Higher preoperative NLR was associated with significantly increased risks of pathologic, extravesical tumor extension (odds ratio [OR]: 1.07; p=0.03) and lymph node involvement (OR: 1.09; p=0.02). Univariately, 10-yr cancer-specific survival was significantly worse among patients with a preoperative NLR (≥2.7 [51%] vs. <2.7 [64%]; p<0.001). Moreover, on multivariate analysis, increased preoperative NLR was independently associated with greater risks of disease recurrence (hazard ratio [HR]: 1.04; p=0.02), death from bladder cancer (HR: 1.04; p=0.01), and all-cause mortality (HR: 1.03; p=0.01). CONCLUSIONS Elevated preoperative NLR among patients undergoing RC is associated with significantly increased risk for locally advanced disease as well as subsequent disease recurrence, and cancer-specific and all-cause mortality. These data suggest that serum NLR may be a useful prognostic marker for preoperative patient risk stratification, including consideration for neoadjuvant therapy and clinical trial enrollment.

Long-term prognostic significance of primary Gleason pattern in patients with Gleason score 7 prostate cancer: impact on prostate cancer specific survival.

PURPOSE We determined the long-term clinical significance of primary Gleason pattern in patients with Gleason score 7 prostate cancer. MATERIALS AND METHODS We reviewed the records of all patients who underwent bilateral pelvic lymph node dissection and radical retropubic prostatectomy for Gleason score 7 prostate cancer at our institution. All patients who underwent adjuvant hormonal or radiation therapy were excluded from analysis. Patients were monitored for biochemical failure, that is PSA progression, systemic recurrence and cancer specific survival. RESULTS We identified 1,688 patients who met admission criteria, of whom 1,256 (74.4%) had primary Gleason pattern 3 and 432 (25.6%) had primary Gleason pattern 4. Median followup was 6.9 years. At 10 years primary Gleason pattern 3 was associated with increased biochemical recurrence-free survival (48% vs 38%, p <0.001), lower systemic recurrence (8% vs 15%, p <0.001) and higher cancer specific survival (97% vs 93%, p = 0.013) for Gleason primary grades 3 and 4, respectively. All of these end points remained significant on multivariate analysis when controlling for preoperative PSA, seminal vesicle involvement, margin status, DNA ploidy and TNM staging. PSA doubling time was shorter in patients with primary Gleason pattern 4 (1.64 vs 1.01 years). Systemic recurrence and cancer specific survival were associated with a PSA doubling time of less than 1 year. CONCLUSIONS Gleason score 7 prostate cancer is a heterogeneous entity. We should continue to stratify patients according to primary Gleason pattern. Patients with Gleason score 4 + 3 prostate cancer have more aggressive disease and experience higher rates of biochemical failure, systemic recurrence and cancer specific death.

The Implications of Hospital Acquired Adverse Events on Mortality, Length of Stay and Costs for Patients Undergoing Radical Cystectomy for Bladder Cancer

PURPOSE The incidence of hospital acquired adverse events in radical cystectomy and their implications for hospital outcomes and costs remain poorly described. We describe the incidence of hospital acquired adverse events in radical cystectomy, and characterize its relationship with in-hospital mortality, length of stay and hospitalization costs. MATERIALS AND METHODS We identified 10,856 patients who underwent radical cystectomy for bladder cancer at 1,175 hospitals in the Nationwide Inpatient Sample from 2001 to 2008. We used hospital claims to identify adverse events for accidental puncture, decubitus ulcer, deep vein thrombosis/pulmonary embolus, methicillin-resistant Staphylococcus aureus, Clostridium difficile, surgical site infection and sepsis. Logistic regression and generalized estimating equation models were used to test the associations of hospital acquired adverse events with mortality, predicted prolonged length of stay and total hospitalization costs. RESULTS Hospital acquired adverse events occurred in 11.3% of all patients undergoing radical cystectomy (1,228). Adverse events were associated with a higher odds of in-hospital death (OR 8.07, p<0.001), adjusted prolonged length of stay (41.3%) and total costs (

Comparative performance of comorbidity indices for estimating perioperative and 5-year all cause mortality following radical cystectomy for bladder cancer.

54,242 vs

Ki-67 and coagulative tumor necrosis are independent predictors of poor outcome for patients with clear cell renal cell carcinoma and not surrogates for each other

26,306; p<0.001) compared to no adverse events on multivariate analysis. The incremental total costs attributable to hospital acquired adverse events were

Functional and oncological outcomes after orthotopic neobladder reconstruction in women

43.8 million. Postoperative sepsis was associated with the highest risk of mortality (OR 17.56, p<0.001), predicted prolonged length of stay (62.22%) and adjusted total cost (