Ryan Dorin

Super Extended Versus Extended Pelvic Lymph Node Dissection in Patients Undergoing Radical Cystectomy for Bladder Cancer: A Comparative Study

PURPOSE There is evidence from retrospective studies that radical cystectomy with extended pelvic lymph node dissection provides better staging and outcomes than limited lymph node dissection. However, the optimal limits of extended lymph node dissection remain unclear. We compared oncological outcomes at 2 cystectomy centers where 2 different extended lymph node dissection templates are practiced to determine whether removing lymphatic tissue up to the inferior mesenteric artery confers an additional survival advantage. MATERIALS AND METHODS Patients undergoing radical cystectomy and extended lymph node dissection with curative intent from 1985 to 2005 were included in analysis if they met certain criteria, including clinically organ confined urothelial bladder carcinoma (cN0M0), pathological stage pT2-pT3, negative surgical margins and no neoadjuvant therapy. Survival and recurrence data were analyzed. RESULTS Demographic data and pathological subgroup distribution (pT2 and pT3) were similar in the 554 University of Southern California and 405 University of Bern patients. University of Southern California patients had higher median number of lymph nodes removed than University of Bern patients (38 vs 22, p <0.0001) and a higher incidence of lymph node metastasis (35% vs 28%, p = 0.02). However, the University of Southern California and University of Bern groups had similar 5-year recurrence-free survival for pT2pN0-2 (57% vs 67%) and pT3pN0-2 (32% vs 34%) disease (p = 0.55 and 0.44, respectively). The overall recurrence rate was equal at the 2 institutions (38%). CONCLUSIONS Meticulous extended lymph node dissection up to the mid-upper third of the common iliac vessels appears to provide survival and recurrence outcomes similar to those of a super extended template up to the inferior mesenteric artery. Complete skeletonization in the extended lymph node dissection template is more important than nodal yield. This does not exclude the possibility that certain patient subgroups with suspicious nodes or after neoadjuvant chemotherapy may benefit from more extensive lymph node dissection.

Lymph Node Dissection Technique Is More Important Than Lymph Node Count in Identifying Nodal Metastases in Radical Cystectomy Patients: A Comparative Mapping Study

BACKGROUND The value of lymph node dissection (LND) in the treatment of bladder urothelial carcinoma is well established. However, standards for the quality of LND remain controversial. OBJECTIVE We compared the distribution of lymph node (LN) metastases in a two-institution cohort of patients undergoing radical cystectomy (RC) using a uniformly applied extended LND template. DESIGN, SETTING, AND PARTICIPANTS Patients undergoing RC at the University of Southern California (USC) Institute of Urology and at Oregon Health Sciences University (OHSU) were included if they met the following criteria: (1) no prior pelvic radiotherapy or LND; (2) lymphatic tissue submitted from all nine predesignated regions, including the paracaval and para-aortic LNs; (3) bladder primary; and (4) category M0 disease. The number and location of LN metastases were prospectively entered into corresponding databases. MEASUREMENTS LN maps were constructed and correlated with preoperative and pathologic characteristics. Kaplan-Meier curves were constructed to estimate overall survival (OS) and recurrence free survival (RFS) among LN-positive (LN+) patients. RESULTS AND LIMITATIONS Inclusion criteria were met by 646 patients (439 USC, 207 OHSU), and 23% had LN metastases at time of cystectomy. Although there was a difference in the median per-patient LN count between institutions, there were no significant interinstitutional differences in the incidence or distribution of positive LNs, which were found in 11% of patients with ≤pT2b and in 44% of patients with ≥pT3a tumors. Among LN+ patients, 41% had positive LNs above the common iliac bifurcation. Estimated 5-yr RFS and OS rates for LN+ patients were 45% and 33%, respectively, and did not differ significantly between institutions. CONCLUSIONS LN metastases in regions outside the boundaries of standard LND are common. Adherence to meticulous dissection technique within an extended template is likely more important than total LN count for achieving optimal oncologic outcomes.

Early Complications of Cystectomy After High Dose Pelvic Radiation

PURPOSE Radical cystectomy in patients with a history of pelvic radiation therapy is often a challenging and morbid procedure. We report early complication rates in patients undergoing cystectomy and urinary diversion after high dose pelvic radiation. MATERIALS AND METHODS From 1983 to 2008, 2,629 patients underwent cystectomy with urinary diversion at a single institution. Of these patients 148 received 60 Gy or greater pelvic radiation therapy before surgery. Patient medical records were retrospectively reviewed and any complication within 90 days of surgery was graded using the Clavien-Dindo system. RESULTS Median patient age was 74 years with a median American Society of Anesthesiologists score of 3. Patients received a median of 70 Gy pelvic radiation therapy a median of 2.3 years before surgery. Urinary diversions performed were ileal conduit in 65 patients (43.9%), continent cutaneous pouch in 35 (23.6%) and orthotopic neobladder in 48 (32.4%). A total of 335 early complications were identified. The highest grade complication was 0 in 23% of the patients, grade 1 in 12.2%, grade 2 in 32.4%, grade 3 in 18.9%, grade 4 in 7.4% and grade 5 in 6.1%. Age older than 65 years and American Society of Anesthesiologists score were statistically significant predictors of postoperative complications (p=0.0264 and p=0.0252, respectively). The type of urinary diversion did not significantly affect the grade distribution or number of early complications per patient (p=0.7444 and p=0.1807, respectively). CONCLUSIONS The early complication rate using a standardized reporting system in patients undergoing radical cystectomy after radiation therapy is higher than previously published in nonirradiated subjects. Age and American Society of Anesthesiologists score but not urinary diversion type were associated with early complications in this population.

Unaltered oncological outcomes of radical cystectomy with extended lymphadenectomy over three decades

To evaluate oncological outcome trends over the last three decades in patients after radical cystectomy (RC) and extended pelvic lymph node (LN) dissection.

Neoadjuvant chemotherapy with gemcitabine/cisplatin vs. methotrexate/vinblastine/doxorubicin/cisplatin for muscle-invasive urothelial carcinoma of the bladder: A retrospective analysis from the University of Southern California☆

OBJECTIVES We evaluated pathologic and survival outcomes of GC (gemcitabine/cisplatin) and methotrexate/vinblastine/doxorubicin/cisplatin (M-VAC) neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS A retrospective analysis of prospectively collected data on 116 patients who received NAC (GC: n = 58; M-VAC: n = 58) before radical cystectomy and superextended pelvic lymph node dissection for clinical stage T2-4N0M0 bladder cancer was performed. The outcomes were complete response rate (CRR; pT0N0), partial response rate (PRR; pT0N0, pTaN0, pT1N0, or pTisN0), overall mortality (OM), and recurrence. The Kaplan-Meier method and multivariable Cox regression analysis were used to analyze OM. The cumulative incidence method and Fine and Grays competing risk regression analysis were used to analyze recurrence. RESULTS The median follow-up duration was 2.1 years for the GC group and 7.4 years for the M-VAC group (P < 0.001). There were no statistically significant differences between the GC and M-VAC groups with regard to CRR (27.3% vs. 17.1%, P = 0.419) or PRR (45.5% vs. 37.1%, P = 0.498). The predicted 5-year freedom from OM rate (P = 0.634) and cumulative incidence of recurrence rate (P = 0.891) did not differ between the GC and M-VAC groups. Multivariable analysis showed that there was no independent association between type of NAC and OM (P = 0.721) or recurrence (P = 0.065). CONCLUSIONS Pathologic and survival outcomes did not differ in patients who received GC and M-VAC NAC. These data support the use of the GC regimen in the neoadjuvant setting.

Critical Evaluation of the American Joint Committee on Cancer TNM Nodal Staging System in Patients with Lymph Node–Positive Disease after Radical Cystectomy

BACKGROUND The current 7th edition of the American Joint Committee on Cancer TNM staging system for bladder cancer stages lymph node (LN)-positive disease based on LN location rather than LN size. In addition, common iliac LNs are now considered regional LNs. Whether these changes improve prognostication for node-positive patients, however, remains unclear. OBJECTIVE To investigate whether the 7th edition of the TNM nodal staging system provides superior prognostication compared with the 6th edition. DESIGN, SETTING, AND PARTICIPANTS Patients between 2002 and 2008 with LN metastases after radical cystectomy combined with extended or superextended LN dissection were included. Patients were staged using both TNM staging systems. Median follow-up was 54 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Kaplan-Meier curves were used to estimate overall survival (OS) and recurrence-free survival (RFS). Log-rank tests and Cox proportional hazard regression models were used to test associations of pathologic variables with OS and RFS. RESULTS AND LIMITATIONS Included were 146 patients with LN metastases of whom 131 patients underwent superextended LN dissection and 15 patients underwent extended LN dissection. Although in the 7th TNM edition many patients moved from the N2 category to the N3 category, RFS did not significantly differ within the nodal subgroups in either editions. LN metastases at or above the aortic bifurcation were not associated with decreased RFS (p=0.67). On multivariable analysis, the presence of extravesical disease (hazard ratio [HR]: 2.84; p=0.002), absence of adjuvant chemotherapy (HR: 0.32; p<0.0001), and more than six positive LNs (HR: 2.72; p=0.007) were associated with decreased RFS. This was a retrospective study with inherent limitations. CONCLUSIONS LNs at or above the aortic bifurcation should be considered regional LNs. Neither the 6th nor the 7th TNM staging system performed well as a prognostic tool. A better staging system for LN-positive bladder cancer needs to be developed.

Outcomes after radical prostatectomy for patients with clinical stages T1-T2 prostate cancer with pathologically positive lymph nodes in the prostate-specific antigen era

OBJECTIVES To evaluate the outcomes of radical prostatectomy (RP) and pelvic lymph node dissection (PLND) for clinically organ confined prostate cancer (CaP) with regional lymph node metastases (pN1) treated in the era of prostate-specific antigen (PSA) screening. MATERIALS AND METHODS A single institution cohort of 2,487 men with cT1-T2 CaP treated with open radical prostatectomy and pelvic lymph node dissection between 1988 and 2008 were analyzed. Kaplan-Meier and Cox proportional regression models were used to analyze overall survival (OS), clinical recurrence-free survival (cRFS), and biochemical recurrence-free survival (bRFS). RESULTS Overall, 150 out of 2,487 patients (6%) had pN1 disease, with a median follow-up of 10.4 years. The predicted 10-year OS, cRFS, and bRFS rates for patients with pN0 and pN1 were 86% and 74% (Log rank P < 0.001), 97% and 84% (Log rank P < 0.001), and 88% and 57% (Log rank P < 0.001), respectively. In the subset of pN1 patients treated with surgery only (n = 49), the predicted 10-year OS, cRFS, and bRFS rates were 81%, 80%, and 59%, respectively. Exploratory univariate regression analysis showed that age (P = 0.003), total number of lymph nodes identified (P = 0.040), and total number of positive lymph nodes identified (P = 0.004) were associated with OS. Total number of positive lymph nodes (LNs) identified was also significantly associated with cRFS (P = 0.05). CONCLUSIONS The incidence of pN1 in patients with cT1-T2 CaP treated with surgery in the era of PSA screening was low. RP and PLND demonstrated therapeutic efficacy in a subset of pN1 patients treated with surgery alone.

Extended lymphadenectomy in bladder cancer.

Purpose of review Radical cystectomy with pelvic lymph node dissection (PLND) is the preferred treatment for invasive bladder cancer. It not only results in the best disease-free term survival rates, but also provides the most accurate disease staging and most effective local symptom control. Recent investigations have demonstrated a clinical benefit to performance of an extended PLND, including all lymphatic tissue to the level of the aortic bifurcation. This review will summarize recent findings regarding the clinical benefits of radical cystectomy with extended lymphadenectomy, and will also examine the latest surgical techniques for optimizing the performance of this technically demanding procedure. Recent findings Recent studies have demonstrated increased recurrence-free survival and overall survival rates in patients undergoing radical cystectomy with extended PLND, even in cases of pathologically lymph node negative disease. The growing use of minimally invasive techniques has prompted interest in robotic radical cystectomy and extended PLND, and recent reports have demonstrated the feasibility of this technique. The standardization of extended PLND templates has also been a focus of contemporary research. Summary Contemporary research strongly suggests that all patients undergoing radical cystectomy for bladder cancer should undergo concomitant extended PLND. Randomized trials are still needed to confirm the benefits of extended over ‘standard’ PLND, and to clarify which patients may receive the greatest benefit from this procedure.

The Impact of Body Mass Index on Perioperative Outcomes in Robot-Assisted Laparoscopic Partial Nephrectomy

BACKGROUND AND PURPOSE Obese patients undergoing surgical procedures are at increased risk for perioperative morbidity. The purpose of this study is to determine whether there is an association with body mass index (BMI), clinicopathologic features, and perioperative outcomes and complications in patients undergoing robot-assisted laparoscopic partial nephrectomy (RPN). PATIENTS AND METHODS Medical records of 283 patients who underwent RPN between 2007 and 2012 were reviewed from an Institutional Review Board approved database. We analyzed the association of perioperative outcomes and complications of the surgery with BMI and clinicopathologic features using analysis of variance, Kruskal-Wallis test, t test and chi-square-test. Eventually, independent factors associated with perioperative outcomes and complications were studied using univariate and multivariate regression analysis. RESULTS Perioperative outcomes including estimated blood loss (EBL), length of hospital stay (LOS) and operative time (OT) were significantly associated with BMI (P=0.002, P=0.009 and P=0.002, respectively). Warm ischemia time (WIT), perioperative complications, and change in glomerular filtration rate (GFR) before and after surgery were not associated with BMI (P=0.459, P=0.86 and P=0.773). In multivariate analysis, BMI, tumor size≥4 cm, and collecting system invasion were independently associated with EBL and OT. Increased LOS was independently associated with BMI and tumor size ≥4 cm. CONCLUSIONS Increasing BMI was not associated with a significant increase in perioperative complications, WIT, or change in GFR in patients undergoing RPN at a high-volume tertiary medical center. Collecting system invasion or tumor size ≥4 cm and BMI were independently associated with higher EBL, LOS, and OT, however.

Was a Change to a Urologist Owned Pathology Laboratory Associated with a Change in Prostate Biopsy Use

Introduction: We assessed the impact of self‐referral to urologist owned pathology facilities on prostate biopsy practice patterns, clinical decision making and pathology service use. Methods: We reviewed a transrectal ultrasound guided prostate biopsy database during 2 periods, including 1) August 5, 2008 to April 10, 2010 (613 days) when pathology samples were sent to an independent service laboratory, and 2) June 11, 2010 to February 13, 2012 (613 days) when samples were assessed at a urologist owned pathology laboratory. We also examined data on 3 additional preceding equal length periods before urologist ownership to determine baseline biopsy rates. Billing databases were used to identify the number of new patient visits for increased prostate specific antigen and/or abnormal digital rectal examination. The Student t‐test, and Wilcoxon rank sum and chi‐square tests were used for statistical comparisons. Results: All biopsies were obtained using a standard transrectal ultrasound guided prostate biopsy protocol. The biopsy rate in patients with increased or abnormal digital rectal examination was 39% during the urologist owned pathology laboratory era, and 35%, 40%, 35% and 40% during the 4 preceding independent service laboratory periods of equal length. There was no statistically significant difference in patient age, rate of abnormal digital rectal examination or indications for repeat transrectal ultrasound guided prostate biopsy among the periods. The prostate cancer detection rate was 45% in the independent service laboratory era and 46% in the urologist owned pathology laboratory era. Conclusions: Self‐referral of transrectal ultrasound guided prostate biopsy specimens to urologist owned pathology facilities was not associated with a significant variation in the biopsy rate, the repeat biopsy rate, indications triggering repeat biopsy or the cancer detection rate.