Darrel Drachenberg

Circulating levels of interleukin-6 in patients with hormone refractory prostate cancer.

Interleukin‐6 (IL‐6) is a cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities. It is found in high levels in human ejaculate, and has recently been found to regulate prostate‐specific protein expression in prostate cancer cells through nonsteroidal activation of the androgen receptor. IL‐6 may be a candidate mediator of morbidity in patients with metastatic disease. We attempted to evaluate the potential of circulating IL‐6 levels as a marker of disease progression.

Active Surveillance of Small Renal Masses: Progression Patterns of Early Stage Kidney Cancer ☆

BACKGROUND Most early stage kidney cancers are renal cell carcinomas (RCCs), and most are diagnosed incidentally by imaging as small renal masses (SRMs). Indirect evidence suggests that most small RCCs grow slowly and rarely metastasize. OBJECTIVE To determine the progression and growth rates for newly diagnosed SRMs stratified by needle core biopsy pathology. DESIGN, SETTING, AND PARTICIPANTS A multicenter prospective phase 2 clinical trial of active surveillance of 209 SRMs in 178 elderly and/or infirm patients was conducted from 2004 until 2009 with treatment delayed until progression. INTERVENTION Patients underwent serial imaging and needle core biopsies. MEASUREMENTS We measured rates of change in tumor diameter (growth measured by imaging) and progression to ≥ 4 cm, doubling of tumor volume, or metastasis with histology on biopsy. RESULTS AND LIMITATIONS Local progression occurred in 25 patients (12%), plus 2 progressed with metastases (1.1%). Of the 178 subjects with 209 SRMs, 127 with 151 SRMs had>12 mo of follow-up with two or more images, with a mean follow-up of 28 mo. Their tumor diameters increased by an average of 0.13 cm/yr. Needle core biopsy in 101 SRMs demonstrated that the presence of RCC did not significantly change growth rate. Limitations included no central review of imaging and pathology and a short follow-up. CONCLUSIONS This is the first SRM active surveillance study to correlate growth with histology prospectively. In the first 2 yr, the rate of local progression to higher stage is low, and metastases are rare. SRMs appear to grow very slowly, even if biopsy proven to be RCC. Many patients with SRMs can therefore be initially managed conservatively with serial imaging, avoiding the morbidity of surgical or ablative treatment.

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

Study Type – Therapy (case series)

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.

Comparison of oncological outcomes for open and laparoscopic radical nephroureterectomy: results from the Canadian Upper Tract Collaboration

Open radical nephroureterectomy (ORNU) with excision of the ipsilateral bladder cuff is a standard treatment for upper tract urothelial carcinoma (UTUC). However, over the past decade laparoscopic RNU (LRNU) has emerged as a minimally invasive surgical alternative. Data comparing the oncological efficacy of ORNU and LRNU have reported mixed results and the equivalence of these surgical techniques have not yet been established. We found that surgical approach was not independently associated with overall or disease‐specific survival; however, there was a trend toward an independent association between LRNU and poorer recurrence‐free survival (RFS). To our knowledge, this is the first large, multi‐institutional analysis to show a trend toward inferior RFS in patients with UTUC treated with LRNU.

Multifocality rather than tumor location is a prognostic factor in upper tract urothelial carcinoma

OBJECTIVES Whether a patient has urothelial carcinoma located within the renal pelvis or ureter remains a controversial prognostic indicator in clinical urology. We wished to evaluate whether tumor location is associated with recurrence in patients undergoing nephroureterectomy for upper tract urothelial cancer in a large volume patient cohort. SUBJECTS AND METHODS We created a retrospective database of patients from 7 academic centers throughout Canada who underwent nephroureterectomy for upper tract urothelial carcinoma. Patient demographics as well as pathologic and surgical factors were analyzed to evaluate any statistical association between tumor location and overall survival, disease-free survival, and disease-specific survival. RESULTS A total of 1,029 patients had data available for analysis with a mean follow up of 3.2 years. Kaplan Meier 5-year disease-free survivals (DFS) were 46%, 37%, and 19% for renal pelvis tumors, ureteric tumors, and multifocal tumors respectively. There was no association between the location of the tumor and the DFS, however, disease involving both the ureter and renal pelvis was associated with lower DFS and overall survival (OS) (P < 0.001). CONCLUSIONS Tumor location does not appear to have any influence on the risk of recurrence of disease following nephroureterectomy in this large patient cohort. However, multifocal tumors involving both the ureter and renal pelvis had a significantly worse prognosis and should be considered for more aggressive management.

Pathological Upstaging of Clinical T1 to Pathological T3a Renal Cell Carcinoma: A Multi-institutional Analysis of Short-term Outcomes

OBJECTIVE To determine the oncological impact of pathological upstaging among patients with clinical T1 (cT1) disease treated by partial nephrectomy or radical nephrectomy. METHODS The Canadian Kidney Cancer Information System comprises a prospectively maintained multi-institutional database for patients with renal cell carcinoma. Nonmetastatic, cT1 renal cell carcinoma cases were evaluated. Upstaging was defined as pathological T3a disease. Multivariate Cox regression analysis identified predictors for recurrence (local recurrence and/or metastatic disease) whereas logistic regression identified predictors of pathological upstaging. Kaplan-Meier methods estimated survival. RESULTS Of 1448 eligible cT1 patients, upstaging was observed in 134 (9%). One thousand fifty-eight (73%) were treated by partial nephrectomy. After a median follow-up of 23 months, the 3-year recurrence-free survival was 76% in upstaged patients compared with 93% in those not upstaged (P < .001). Controlling for age, gender, year of surgery, histology, tumor size, surgical approach, and margin status, pathological upstaging was independently associated with disease recurrence (hazard ratio 2.03, 95% confidence interval [CI] 1.12-3.68). Increasing age (odds ratio [OR] 1.02, 95% CI 1.00-1.05), Fuhrman grade (OR 2.47, 95% CI 1.47-4.14), and tumor size (OR 1.16, 95% CI 1.00-1.36) were independently associated with a risk of pathological upstaging. CONCLUSION Pathological upstaging confers a negative prognosis and highlights the importance of accurate clinical staging. A number of factors have been identified, including some attainable by renal biopsy, which may predict upstaging and provide valuable adjunct information to inform risk stratification and management decisions among patients with cT1 renal masses.

Disease progression and kidney function after partial vs. radical nephrectomy for T1 renal cancer

PURPOSE Partial nephrectomy (PN) for early stage renal cancer preserves renal function better than radical nephrectomy (RN) and is generally considered oncologically similar. The Intergroup European Organisation for Research and Treatment of Cancer trial comparing outcomes after PN vs. RN, however, showed reduced overall survival in the PN group. Our aim was to evaluate recurrence, death, and renal function after PN vs. RN for T1 tumors in a Canadian population. MATERIALS AND METHODS From 2000 to 2015, 2,358 patients with a first occurrence of a clinical T1 renal cancer who underwent PN or RN were identified from the Canadian Kidney Cancer Information System. Clinical, surgical, and pathologic parameters were analyzed. Time to progression was compared after PN vs. RN using a Cox proportional hazards model, adjusted for pertinent variables. RESULTS Inclusion criteria were met in 1,615 PN and 743 RN. Preoperative characteristics appeared similar in both groups. Time to progression was not different after PN vs. RN, adjusted for potential confounders (hazard ratio = 1.17 [95% CI: 0.8-1.72, P = 0.42]). Postoperative estimated glomerular filtration rate at 1 and 3 years was significantly greater for PN vs. RN in a linear regression model, accounting for preoperative estimated glomerular filtration rate. CONCLUSIONS These results suggest that progression-free survival after PN and RN in patients with T1 renal cancer was similar, but that there was better preservation of renal function after PN. This suggests that both PN and RN have similar oncological efficiency, and that selection of surgical approach should be based on other factors such as technical feasibility, potential complications, and preservation of renal function.