Abstract 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.
Diagnostic ureteroscopic biopsy for upper tract urothelial carcinoma (UTUC) has been hypothesized to increase intravesical recurrence of urothelial carcinoma after radical nephroureterectomy (RNU). ...Moreover, the impact of ureteroscopy without biopsy or percutaneous biopsy on intravesical recurrence remains unknown. Herein, we compared post-RNU intravesical recurrences across UTUC diagnostic modalities.
Patients undergoing RNU at our institution between 1995 and 2019 were categorized by UTUC diagnostic modality: 1) no ureteroscopy or percutaneous biopsy; 2) percutaneous biopsy; 3) ureteroscopy without biopsy; 4) ureteroscopic biopsy. Intravesical recurrences were compared using Kaplan-Meier analyses and Cox-proportional hazard models. Results of group 4 vs 1 were pooled with the literature using a fixed effects meta-analysis.
In a cohort of 834 RNU patients, 210 (25.2%) had undergone no ureteroscopy, 57 (6.6%) percutaneous biopsy, 125 (15.0%) ureteroscopy without biopsy, and 442 (53.0%) ureteroscopic biopsy. Two-year intravesical recurrence rates were 15.0%, 12.7%, 18.4%, and 21.9% for groups 1 through 4, respectively (p=0.09). Multivariable analysis found that group 4 had increased intravesical recurrences (HR 1.40, p=0.04) relative to group 1 while group 2 (HR 1.07, p=0.87) and group 3 (HR 1.15, p=0.54) did not. Group 4 remained associated with intravesical recurrence on subset analyses accounting for post-RNU surveillance cystoscopy frequency. On meta-analysis including 11 other series, ureteroscopic biopsy was associated with intravesical recurrence (HR 1.47, p <0.01).
Ureteroscopic biopsy before RNU, but not percutaneous biopsy or ureteroscopy without biopsy, was associated with increased intravesical recurrence. Clinical trials of intravesical chemotherapy after ureteroscopic biopsy are warranted to reduce intravesical recurrences.
Abstract 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.
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.
Purpose Radical cystectomy continues to be associated with a nonnegligible risk of perioperative death and all cause mortality in the years after surgery remains relatively high. We investigated the ...comparative ability of various comorbidity indices to predict perioperative and 5-year all cause mortality after radical cystectomy. Materials and Methods We evaluated 891 patients who underwent radical cystectomy between 1994 and 2005. The associations of American Society of Anesthesiologists (ASA) score, Charlson comorbidity index, Elixhauser index and ECOG (Eastern Cooperative Oncology Group) performance status with outcomes were assessed using Cox regression models. Model performance was compared with area under receiver operating curves. Results A total of 33 (3.7%) patients died within 90 days of radical cystectomy. On multivariate analysis locally advanced pathological tumor stage (HR 4.86, p = 0.002) as well as Elixhauser index (HR 1.48, p = 0.002), ASA score (HR 3.17, p = 0.001) and ECOG (HR 2.40, p <0.0001) were significantly associated with 90-day perioperative mortality. Median followup after radical cystectomy was 10.1 years, during which time 576 patients died. Charlson comorbidity index (HR 1.23, p <0.0001), Elixhauser index (HR 1.28, p <0.0001), ASA score (HR 1.44, p = 0.007) and ECOG (HR 1.97, p <0.0001) were independent predictors of 5-year all cause mortality. Moreover Charlson comorbidity index (AUC 0.798, p <0.0001), Elixhauser index (AUC 0.770, p = 0.03) and ECOG (AUC 0.769, p = 0.03) significantly enhanced the performance of a base model which did not include comorbidity status (AUC 0.757) to predict 5-year all cause mortality. Conclusions Comorbidity status is predictive of perioperative death and 5-year all cause mortality after radical cystectomy and, therefore, should be incorporated into patient counseling and risk stratification models. Further prospective studies are warranted to overcome the retrospective limitations in determining the relative prognostic value of various comorbidity indices.
Purpose We evaluated the long-term natural history of renal function after radical cystectomy with urinary diversion and determined factors associated with decreased renal function. Materials and ...Methods We reviewed the records of 1,631 patients who underwent radical cystectomy between 1980 and 2006. The estimated glomerular filtration rate was calculated preoperatively and at various intervals after surgery. A renal function decrease was defined as a greater than 10 ml per minute/1.73 m2 reduction in the estimated glomerular filtration rate. Multivariate analysis was done to evaluate the association of clinicopathological features, incontinent vs continent diversion type and postoperative complications with decreased renal function. Results A total of 1,241 patients (76%) underwent incontinent diversion and 390 (24%) underwent continent diversion. Median followup after radical cystectomy in patients alive at last followup was 10.5 years (IQR 7.1, 15.3). The median preoperative estimated glomerular filtration rate was higher in the continent diversion cohort (67 vs 59 ml per minute/1.73 m2 , p <0.0001). This difference was maintained until 7 years postoperatively, after which no difference was noted in renal function by diversion type. By 10 years after radical cystectomy the risk of a renal function decrease was similar for incontinent and continent diversion (71% and 74%, respectively, p = 0.13). On multivariate analysis risk factors associated with decreased renal function included age (HR 1.03, p <0.0001), preoperative estimated glomerular filtration rate (HR 1.05, p <0.0001), chronic hypertension (HR 1.2, p = 0.01), postoperative hydronephrosis (HR 1.2, p = 0.03), pyelonephritis (HR 1.3, p = 0.01) and ureteroenteric stricture (HR 1.6, p <0.0001). Conclusions Decreased renal function is noted in most patients during long-term followup after radical cystectomy. Postoperative hydronephrosis, pyelonephritis and ureteroenteric stricture represent potentially modifiable factors associated with a decrease. Choice of urinary diversion was not independently associated with decreased renal function.
Purpose We assess the impact of obesity, as measured conventionally by body mass index vs excess adiposity as measured by fat mass index, on mortality after radical cystectomy for bladder cancer, ...adjusting for the presence of skeletal muscle wasting. Materials and Methods This retrospective cohort study included 262 patients treated with radical cystectomy for bladder cancer between 2000 and 2008 at the Mayo Clinic. Lumbar skeletal muscle and adipose compartment areas were measured on preoperative imaging. Overall survival was compared according to gender specific consensus fat mass index and skeletal muscle index thresholds as well as conventional body mass index based criteria. Predictors of all cause mortality were assessed by multivariable modeling. Results Increasing body mass index correlated with improved overall survival (p=0.03) while fat mass index based obesity did not (p=0.08). After stratification by sarcopenia, no obesity related 5-year overall survival benefit was observed (68% vs 51.4%, p=0.2 obese vs normal and 40% vs 37.4%, p=0.7 sarcopenia vs sarcopenic/obese). On multivariable analysis class I obesity according to body mass index (HR 0.79, p=0.33) or fat mass index criteria (HR 0.85, p=0.45) was not independently associated with all cause mortality after adjusting for sarcopenia (HR 1.7, p=0.01) as well as age, performance status, pTN stage and smoking status. However, in patients with normal lean muscle mass each 1 kg/m2 increase in weight or adipose mass was associated with a 7% to 14% decrease in all cause mortality. Conclusions After adjusting for lean muscle wasting, neither measurements of obesity nor adiposity were significantly associated with all cause mortality in patients treated with radical cystectomy, although subanalyses suggest a potential benefit among those with normal lean muscle mass.
Many early universe theories predict the creation of Primordial Black Holes (PBHs). PBHs could have masses ranging from the Planck mass to 105 solar masses or higher depending on the size of the ...universe at formation. A Black Hole (BH) has a Hawking temperature which is inversely proportional to its mass. Hence a sufficiently small BH will quasi-thermally radiate particles at an ever-increasing rate as emission lowers its mass and raises its temperature. The final moments of this evaporation phase should be explosive and its description is dependent on the particle physics model. In this work we investigate the final few seconds of BH evaporation, using the Standard Model and incorporating the most recent Large Hadron Collider (LHC) results, and provide a new parameterization for the instantaneous emission spectrum. We calculate for the first time energy-dependent PBH burst light curves in the GeV/TeV energy range. Moreover, we explore PBH burst search methods and potential observational PBH burst signatures. We have found a unique signature in the PBH burst light curves that may be detectable by GeV/TeV gamma-ray observatories such as the High Altitude Water Cerenkov (HAWC) observatory. The implications of beyond the Standard Model theories on the PBH burst observational characteristics are also discussed, including potential sensitivity of the instantaneous photon detection rate to a squark threshold in the 5–10 TeV range.
We sought to independently validate the AJCC (American Joint Committee on Cancer) 8th edition prostate cancer staging classification, which includes the elimination of pT2 subcategories and the ...reclassification of patients with prostate specific antigen 20 ng/ml or greater and Gleason Grade Group 5 as stage groups III-A and III-C, respectively.
We identified 13,839 men who underwent radical prostatectomy at Mayo Clinic between 1987 and 2011 from our institutional registry. Outcomes included biochemical recurrence-free, metastasis-free and cancer specific survival. Kaplan-Meier analyses and Cox regression models with the c-index were used.
Median followup was 10.5 years (IQR 7.1–15.3). Among patients with pT2 prostate cancer the subclassification demonstrated limited discrimination for biochemical recurrence-free, metastasis-free and cancer specific survival (c-index 0.531, 0.545 and 0.525, respectively). At the same time patients with 7th edition stage group II prostate cancer and prostate specific antigen 20 ng/ml or greater had significantly worse 15-year biochemical recurrence-free survival (42.2% vs 58.8%), metastasis-free survival (78.2% vs 88.8%) and cancer specific survival (88.0% vs 94.4%, all p <0.001) than patients with 7th edition stage group II prostate cancer and prostate specific antigen less than 20 ng/ml. However, patients with 7th edition stage group II prostate cancer and prostate specific antigen 20 ng/ml or greater had significantly better 15-year biochemical recurrence-free survival (42.2% vs 31.3%, p = 0.007), metastasis-free survival (78.2% vs 68.0%, p <0.001) and cancer specific survival (88.0% vs 83.4%, p = 0.01) than patients with 7th edition stage group III. Also, patients with 7th edition stage group II prostate cancer and Gleason Grade Group 5 had significantly worse 15-year biochemical recurrence-free survival (37.1% vs 57.9%, p <0.001), metastasis-free survival (63.8% vs 88.5%, p <0.001) and cancer specific survival (73.0% vs 94.3%, p <0.001) than patients with 7th edition stage group II prostate cancer and Gleason Grade Group 1-4 as well as worse 15-year cancer specific survival (73.0% vs 83.4%, p = 0.005) than patients with 7th edition stage group III prostate cancer.
Our data support the changes in the new AJCC classification.
Abstract Objective To compare the predictive ability for oncologic outcomes among current tumor size cut-points and clinically relevant alternatives in order to determine which are optimal. Methods ...Patients who underwent radical or partial nephrectomy between 1970-2010 for T1-2Nx/N0M0 renal cell carcinoma (RCC) were identified. Associations between tumor size and progression-free survival (PFS) and cancer-specific survival (CSS) were evaluated using Kaplan-Meier analyses and Cox models. Predictive ability was assessed using c-indexes. Results The cohort included 3304 patients with a median age of 63 years (IQR 53,70). Median follow-up among survivors was 9.9 years (IQR 6.9,14.3). There were 536 patients who progressed and who 354 died from RCC. For RCC tumors ≤3.0cm, 10-year PFS and CSS rates were 93-95% and 97-99%, respectively. For tumors >3.0-4.0cm, PFS and CSS began to decline (91% and 95%, respectively), with further gradual declines in PFS and CSS with increasing tumor size. Plots of hazard ratios for progression and RCC-death as a function of tumor size did not reveal major inflection points. Differences in discrimination based on various combinations of tumor-size cut-points for progression or RCC-death were small, with c-indexes ranging between 0.691-0.704 and 0.734-0.750, respectively. Conclusions RCC tumors ≤3.0cm in size are associated with favorable outcomes. Thereafter, risks of progression and RCC-death increase gradually with tumor size, with no compelling biological reason to endorse a given cut-point over another.
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