Ilias Cagiannos

International Validation of a Preoperative Nomogram for Prostate Cancer Recurrence After Radical Prostatectomy

PURPOSE We evaluated the predictive accuracy of a recently published preoperative nomogram for prostate cancer that predicts 5-year freedom from recurrence. We applied this nomogram to patients from seven different institutions spanning three continents. METHODS Clinical data of 6,754 patients were supplied for validation, and 6,232 complete records were used. Nomogram-predicted probabilities of 60-month freedom from recurrence were compared with actual follow-up in two ways. First, areas under the receiver operating characteristic curves (AUCs) were determined for the entire data set according to several variables, including the institution where treatment was delivered. Second, nomogram classification-based risk quadrants were compared with actual Kaplan-Meier plots. RESULTS The AUC for all institutions combined was 0.75, with individual institution AUCs ranging from 0.67 to 0.83. Nomogram predictions for each risk quadrant were similar to actual freedom from recurrence rates: predicted probabilities of 87% (low-risk group), 64% (intermediate-low-risk group), 39% (intermediate-high-risk group), and 14% (high-risk group) corresponded to actual rates of 86%, 64%, 42%, and 17%, respectively. The use of neoadjuvant therapy, variation in the prostate-specific antigen recurrence definitions between institutions, and minor differences in the way the Gleason grade was reported did not substantially affect the predictive accuracy of the nomogram. CONCLUSION The nomogram is accurate when applied at international treatment institutions with similar patient selection and management strategies. Despite the potential for heterogeneity in patient selection and management, most predictions demonstrated high concordance with actual observations. Our results demonstrate that accurate predictions may be expected across different patient populations.

Contemporary outcomes of 2287 patients with bladder cancer who were treated with radical cystectomy: a Canadian multicentre experience.

Study Type – Therapy (case series)

URETEROPELVIC JUNCTION DISRUPTION SECONDARY TO BLUNT TRAUMA: EXCRETORY PHASE IMAGING (DELAYED FILMS) SHOULD HELP PREVENT A MISSED DIAGNOSIS

PURPOSE Ureteropelvic junction disruption is a rare condition which is often diagnosed after some delay. The aim of this study is to examine the current status of this entity and to determine if improvements could be made in the diagnosis. MATERIALS AND METHODS We evaluated 5 consecutive adult cases of ureteropelvic junction disruption secondary to blunt trauma and compared the findings to those reported in literature. RESULTS The diagnosis was delayed by at least 24 hours in 4 of the 5 cases (80%). Compared to the literature, in which most delays in diagnosis were the result of genitourinary tract imaging being omitted, most of our delays (3 cases) were a result of the initial contrast enhanced spiral (helical) computerized tomography (CT) failing to provide the diagnosis. This failure occurred because of either absence of contrast extravasation (2 cases) or only subtle extravasation (1 case), which was not recognized by the radiologist. The delay in diagnosis resulted in added morbidity in all circumstances. CONCLUSIONS Ureteropelvic junction disruption continues to be diagnosed late in a large proportion of cases. Absence of gross contrast extravasation on nephrogram phase scanning using spiral CT may not exclude a major injury of the ureteropelvic junction. Addition of delayed CT of the kidney 5 to 8 minutes or longer after contrast material injection (during the excretory phase) may increase the probability of extravasation being demonstrated and, thus, reduce the possibility of missing a ureteropelvic junction disruption.

Preservation of Renal Function Following Partial or Radical Nephrectomy Using 24-Hour Creatinine Clearance

OBJECTIVE To compare the effect on renal function of partial and radical nephrectomy using creatinine clearance measurements from 24-hr urine collection. METHODS All patients with a solid enhancing renal mass suspicious for renal cell carcinoma, a normal contralateral kidney, and not dialysis dependent were enrolled in this prospective cohort study. Patients were treated with partial or radical nephrectomy by one urologist. Creatinine clearance (CrCl) measurements were prospectively obtained by 24-hr urine collection preoperatively, and at 3, 6, and 12 mo postoperatively. Mean change in creatinine clearance from baseline was compared at 3, 6, and 12 mo. Serum creatinine and Cockcroft-Gault calculations were also performed for comparison. Mixed model analysis incorporating patient and tumor characteristics and the procedure type was performed in SAS Version 9.1. RESULTS Sixty-three consecutive patients were enrolled in this study. The partial nephrectomy (n=26) and radical nephrectomy (n=37) groups were similar with respect to age, sex, presence of hypertension, vascular disease, diabetes mellitus, and angiotensin converting enzyme inhibitor or receptor blocker use. The postoperative change in creatinine clearance was significantly less (p-value < 0.0001) in the partial nephrectomy group (-0.09mL/s, -6.1%) compared to the radical nephrectomy group (-0.56mL/s, -31.6%). Linear regression analysis showed intervention type (partial vs. radical nephrectomy) was the most significant predictor of change in creatinine clearance (p-value < 0.0001). CONCLUSIONS There is significantly less deterioration in the overall renal function of patients who are treated with partial nephrectomy compared to radical nephrectomy. This highlights the importance of performing nephron-sparing surgery on appropriate patients.

Association of Diagnostic Radiation Exposure and Second Abdominal-Pelvic Malignancies After Testicular Cancer

PURPOSE The evidence associating cancer risk with diagnostic radiation exposure is unclear. Men recovering from low-grade testicular cancer frequently undergo serial abdominal-pelvic computerized tomography (CT) scanning to monitor for recurrent disease. METHODS We used population-based administrative data sets to identify every incident case of testicular cancer between 1991 and 2004 in Ontario, Canada. We excluded those with previous cancer, concurrent radiation therapy, retroperitoneal lymph node dissection, or fewer than 5 years observation. Patients were observed until the occurrences of death or development of a second abdominal-pelvic malignancy or until December 31, 2009. RESULTS A total of 2,569 men (mean age, 34.7 years; standard deviation, 10.2) were observed for a median of 11.2 years (interquartile range [IQR], 8.3 to 14.3). During the first 5 years after diagnosis, men underwent a median of 10 computed tomography (CT) scans (IQR, 4 to 18) of the abdominal-pelvic area, and they were exposed to a median of 110 mSv of radiation from radiologic investigations (IQR, 44 to 190). After this, 14 men were diagnosed with a second abdominal-pelvic malignancy (rate, five per 10,000 patient-years observation, 95% CI, three to eight); the most common diagnoses were colorectal and kidney malignancies. Radiation exposure was not associated with an excess risk of second cancers (hazard ratio per 10 mSv increase, 0.99; 95% CI, 0.95 to 1.04). This association did not change if men observed for fewer than 5 years were included in the analysis (hazard ratio, 1.00; 95% CI, 0.96 to 1.04). CONCLUSION Second malignancies of the abdomen-pelvis are uncommon in men with low-grade testicular cancer. In this study, the risk of second cancer was not associated with the amount of diagnostic radiation exposure.

Peri-operative morbidity associated with radical cystectomy in a multicenter database of community and academic hospitals.

Objective To characterize the frequency and timing of complications following radical cystectomy in a cohort of patients treated at community and academic hospitals. Patients and Methods Radical cystectomy patients captured from NSQIP hospitals from January 1 2006 to December 31 2012 were included. Baseline information and complications were abstracted by study surgical clinical reviewers through a validated process of medical record review and direct patient contact. We determined the incidence and timing of each complication and calculated their associations with patient and operative characteristics. Results 2303 radical cystectomy patients met inclusion criteria. 1115 (48%) patients were over 70 years old and 1819 (79%) were male. Median hospital stay was 8 days (IQR 7–13 days). 1273 (55.3%) patients experienced at least 1 post-operative complication of which 191 (15.6%) occurred after hospital discharge. The most common complication was blood transfusion (n = 875; 38.0%), followed by infectious complications with 218 (9.5%) urinary tract infections, 193 (8.4%) surgical site infections, and 223 (9.7%) sepsis events. 73 (3.2%) patients had fascial dehiscence, 82 (4.0%) developed a deep vein thrombosis, and 67 (2.9%) died. Factors independently associated with the occurrence of any post-operative complication included: age, female gender, ASA class, pre-operative sepsis, COPD, low serum albumin concentration, pre-operative radiotherapy, pre-operative transfusion >4 units, and operative time >6 hours (all p<0.05). Conclusion Complications remain common following radical cystectomy and a considerable proportion occur after discharge from hospital. This study identifies risk factors for complications and quality improvement needs.

Surveillance guidelines based on recurrence patterns after radical cystectomy for bladder cancer: the Canadian Bladder Cancer Network experience

Study Type – Prognosis (cohort)

Adjuvant chemotherapy for upper-tract urothelial carcinoma treated with nephroureterectomy: Assessment of adequate renal function and influence on outcome

OBJECTIVES Upper-tract urothelial carcinoma (UTUC) is associated with poor outcomes. Our aim was to assess adequacy of renal function and evaluate the role of adjuvant chemotherapy (AC) in patients with UTUC treated by radical nephroureterectomy (RNU) in a universal health care system. MATERIALS AND METHODS Retrospective data from 1,029 patients treated with RNU across 10 Canadian academic centers were collected. Tested variables included various clinico-pathological parameters, the use of perioperative chemotherapy, preoperative and postoperative creatinine values, and estimated glomerular filtration rates (eGFR). Univariable and multivariable Cox regression models addressed overall survival and disease-specific survival after surgery. Kaplan-Meier survival curves were used to compare outcomes in patients who received or did not receive AC. RESULTS Median age of patients was 70 years with a median follow-up of patients who were alive of 26 months. The median preoperative and postoperative eGFR rates were 59 mL/min/1.73 m(2) and 47 mL/min/1.73 m(2), respectively. Using a cutoff eGFR of 60, 49% of all the patients and 48% of the patients with ≥ pT3 or pTxN+ or both diseases would have been eligible for cisplatin-based chemotherapy preoperatively and only 18% and 21% of the patients, respectively remained eligible postoperatively. Of the patients who received AC, 75% had an eGFR<60. On multivariate analysis, AC was not prognostic for improved overall survival or disease-specific survival. CONCLUSIONS Chronic kidney disease is common in patients with UTUC. Following RNU, 57% of the high-risk patients with good preoperative renal function became ineligible for cisplatin-based chemotherapy. Use of AC did not translate into improved survival. Whether this is due to inherent biases of retrospective analysis, limited efficacy of AC in patients with UTUC, or use of suboptimal regimen or dose because of poor postoperative renal function requires further evaluation.

The Contemporary Role of Lymph Node Dissection During Nephroureterectomy in the Management of Upper Urinary Tract Urothelial Carcinoma: The Canadian Experience

OBJECTIVE To investigate the association between lymph node dissection (LND) and survival among patients undergoing nephroureterectomy for upper urinary tract urothelial cell carcinoma (UTUC). METHODS This study includes 1029 patients from 10 Canadian institutions who underwent nephroureterectomy between 1990 and 2010. Disease-specific survival (DSS), overall survival (OS), and recurrence-free survival (RFS) were compared for patients with a node-negative LND (N0), node-positive LND (N+), or no LND (Nx) using Kaplan-Meyer analysis and Cox regression analysis. The association between survival and number of positive nodes, number of nodes removed, and ratio of positive nodes to nodes removed was also investigated. RESULTS The median follow-up for the entire cohort was 19.8 months (interquartile range = 7.2-53.8). LND was performed in 276 (26.8%) patients, and 77 (27.9%) had N+ disease. Patients with N+ disease had significantly shorter OS, DSS, and RFS compared with N0 and Nx patients(P < .01). No differences were identified between N0 and Nx patients in any survival categories (P > .05). A ratio of positive nodes to nodes removed ≥ 20% had a per annum hazard ratio of 2.24 (95% confidence interval [CI] 1.18-4.65) for OS, 2.70 (95% CI = 1.25-5.83) for DSS, and 1.94 (95% CI = 1.13-3.32) for RFS. The number of positive nodes and the number of nodes removed were not associated with survival in any survival category (P > .05). CONCLUSION LND during nephroureterectomy provides more accurate staging and prediction of survival; however, it remains uncertain whether LND independently improves survival in patients with UTUC.

PERCENT FREE PROSTATE SPECIFIC ANTIGEN IS NOT AN INDEPENDENT PREDICTOR OF ORGAN CONFINEMENT OR PROSTATE SPECIFIC ANTIGEN RECURRENCE IN UNSCREENED PATIENTS WITH LOCALIZED PROSTATE CANCER TREATED WITH RADICAL PROSTATECTOMY

PURPOSE We studied the controversial relationship of percent free prostate specific antigen (PSA) with organ confined prostate cancer and PSA failure after radical prostatectomy. MATERIALS AND METHODS We tested the characteristics of the percent free PSA monoclonal Immulite DPC Immunoassay (Diagnostic Products Corp., Los Angeles, California) for predicting organ confinement in 698 consecutive unscreened men treated only with radical prostatectomy between 1995 and 2000. In addition, we assessed the ability of percent free PSA to predict post-radical prostatectomy PSA failure, defined as PSA 0.1 ng./ml. or greater, in a subset of 581 men in whom followup was available. All statistical analyses were repeated for stage T1c cancer with PSA between 2 and 10 ng./ml. RESULTS On univariate analyses percent free PSA achieved significance for predicting organ confined disease at all clinical stages (p <0.001) and for stage T1c cancer with PSA between 2 and 10 ng./ml. (p = 0.012). However, significance dissipated after controlling for total PSA, biopsy Gleason sum and clinical stage (p = 0.135 and 0.851, respectively). In univariate Cox models percent free PSA failed to predict PSA failure across stages (p = 0.341), as well as in stage T1c cancer (p = 0.93). In multivariate analyses controlling for traditional PSA biopsy grade and clinical stage (p <0.001), percent free PSA failed to contribute to predicting PSA failure (p = 0.342). In the stage T1c subset biopsy Gleason sum (p <0.001) and PSA (p = 0.018) remained significant, in contrast to percent free PSA (p = 0.237). CONCLUSIONS Percent free PSA has no independent, statistically significant association with organ confined status or posttreatment PSA outcome in unscreened patients who undergo radical prostatectomy for localized prostate cancer.