Tom J.N. Hermans

Variations in pelvic lymph node dissection in invasive bladder cancer: A Dutch nationwide population-based study during centralization of care

OBJECTIVES To assess temporal trends in radical cystectomy (RC) and pelvic lymph node dissection (PLND) and the effect of centralization of care in the Netherlands between 2006 and 2012. PATIENTS AND METHODS This nationwide population-based study included 3524 patients from the Netherlands Cancer Registry who underwent RC as the primary treatment for cT1-4a, N0 or Nx, M0 urothelial carcinoma. Annual application rates of PLND, median LNC, and rates of node-positive disease (pN+) were compared by linear-by-linear association. Multivariable logistic regression was performed to identify patients׳ and hospital characteristics associated with PLND and LNC≥10, and to study associations between LNC and pN+disease. RESULTS In total, 3,191 (91%) patients had PLND during RC and the use increased from 84% in 2006 to 96% in 2012 (P<0.001). Owing to centralization of care in 2010 (at least 10RCs/y/hospital), significantly more patients were treated in high-volume hospitals (≥20RC per year) in 2011 and 2012. PLND use was highest in males, younger patients and in academic, teaching, and high-volume hospitals (≥20RC per year). In 2012, PLND application rates were comparable for academic, teaching, and nonteaching hospitals (P = 0.344). Median LNC increased from 7 in 2006 to 13 in 2012 (P<0.001), 55% had an LNC≥10 (63% in 2012). Furthermore, lymph node count (LNC)≥10 was associated with cT3-4a and, pN+disease, R0 and treatment in academic, teaching, or high-volume hospitals (≥20RC per year). Rate of pN+disease increased from 18% to 24% between 2006 and 2012 (P = 0.014). This trend was significantly associated with increased LNC on a continuous scale (odds ratio = 1.03). CONCLUSIONS After centralization of care, PLND during RC for cT1-4a, N0 or Nx, M0 urothelial carcinoma has become standard in all types of Dutch hospitals. The increase in LNC between 2006 and 2012 was associated with a higher incidence of pN+disease and suggests more adequate template extension and adherence to contemporary guidelines in recent years.

Lymph node count at radical cystectomy does not influence long-term survival if surgeons adhere to a standardized template

INTRODUCTION Multiple bladder cancer studies report that the number of removed lymph nodes (lymph node count [LNC]) at radical cystectomy (RC) is positively associated with survival. Although these reports suggest that LNC can be used as a proxy for surgical quality, all studies used variable or inconsistent pelvic lymph node dissection (PLND) templates. We therefore wished to establish whether LNC at RC influences survival if surgeons adhere to a standardized PLND template. MATERIALS AND METHODS We included 274 patients who underwent RC from January 2005 until December 2012. All RCs were performed in either one of 2 hospitals (hospital A or B) by the same 4 urologists (all from hospital A) and a standardized PLND template was applied. PLND specimens were processed by 2 independent pathology departments (hospital A and B). We used Cox regression analysis to investigate the prognostic value of LNC adjusted for patient characteristics. We also compared LNC between hospitals and surgeons and investigated the effect of both the variables on overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). RESULTS Median LNC was 17 (interquartile range = 12). At a median follow-up of 64.3 months, there was no association between LNC and OS (P = 0.328), CSS (P = 0.645), or DFS (P = 0.450). Median LNC was higher in hospital B than in hospital A (20.0 vs. 16.0, P = 0.003). Median LNC varied significantly among surgeons (12-20, P<0.001). Neither the hospital of surgery nor the surgeon performing PLND influenced OS (P = 0.771 and P = 0.982, respectively), CSS (P = 0.310 and P = 0.691, respectively), or DFS (P = 0.256 and P = 0.296, respectively). CONCLUSION If surgeons adhere to a standardized template, LNC at RC does not affect long-term survival.

Neoadjuvant treatment for muscle-invasive bladder cancer: The past, the present, and the future

BACKGROUND Approximately half of patients who undergo radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) will succumb to metastatic disease. We summarize the evidence for neoadjuvant radiation (NAR), chemo (NAC), and immunotherapy (checkpoint inhibition) prior to RC for MIBC. MATERIALS AND METHODS Data were obtained by a search of PubMed, ClinicalTrials.gov, and Cochrane databases for English language articles published from 1925 up to 2017. RESULTS NAC usage has increased over the last decade, while NAR is rarely administered. Although NAR results in downstaging, its impact on survival is inconclusive. Based on level I evidence, cisplatin-based NAC (CB-NAC) is considered standard of care in cT2-4aN0M0 MIBC. NAC results in a 6% absolute 10-year overall survival (OS) benefit. In-depth analyses of key randomized controlled trials showed that failure to correct for uniform staging, surgical variation, and patient selection compromises the ability to identify factors predictive of response to NAC. The benefit appears to be restricted to patients downstaged to ypT1N0 or less. In these patients, 5-year OS is 80% to 90%. Regarding a number needed to treat of 17, most patients with cT2-4aN0M0 MIBC will be exposed to toxicity without benefit. Possible approaches to reduce overtreatment are suggested in this article and include patient selection, the chosen NAC regimen, and emerging molecular data to predict responsiveness to NAC. Neoadjuvant immunotherapy with checkpoint inhibitors is a promising future perspective currently under investigation. CONCLUSIONS Past studies on NAR show inconclusive results and NAR is rarely administered. Instead, CB-NAC is advised in eligible patients with cT2-4aN0M0 MIBC prior to RC. In the near future, predictive biomarkers will be the key to tailor the use of CB-NAC and reduce harm to nonresponders.

Re: Trends in the Use of Perioperative Chemotherapy for Localized and Locally Advanced Muscle-invasive Bladder Cancer: A Sign of Changing Tides

early chemotherapy, which can be potentially harmful. Many patients have slowly developing disease, low-volume disease, or oligometastatic disease, and do very well with standard-of-care ADT (with or without other local therapies). There are not enough data available for patients with low-volume disease to recommend routine use of chemotherapy, as pointed out in the National Comprehensive Cancer Network guidelines. These trial data challenge how we think about and treat metastatic prostate cancer. We must now critically analyze each individual patient and ascertain which patients are fit enough, are willing to accept the risks, and will truly derive benefit from early chemotherapy. As responsible physicians we must always remember the Hippocratic maxim primum non nocere: above all, do no harm.

Oncologic outcome after laparoscopic radical cystectomy without neoadjuvant or adjuvant therapy with a median follow-up of 32 months.

Introduction: We report the oncological outcome after laparoscopic radical cystectomy (LRC) and standard laparoscopic pelvic lymph node dissection (PLND) without neoadjuvant or adjuvant therapy in the treatment of bladder cancer with a median follow-up of 32 months. Materials and Methods: From September 2006 to January 2011, 40 consecutive patients underwent an LRC and standard laparoscopic PLND, and were included in this prospective observational cohort study. No patient received neoadjuvant or adjuvant therapy. Demographic, perioperative, complication, histopathologic and survival data were collected and analyzed. Results: The 2002 TNM staging for the tumors were: pT0, 4 cases; pTis, 5 cases; pT1, 4 cases; pT2, 7 cases; pT3, 13 cases; pT4, 7 cases. Positive surgical margins were reported in 3 patients (7.5%) and lymph node involvement in 9 patients (23.7%). No patient was lost to follow-up. The overall, cancer-specific and recurrence-free survival rates were 53, 73 and 70% with a median follow-up of 32 months. Eleven patients (27.5%) died of metastatic disease or local recurrence. Nonorgan-confined disease (≥pT3) and primary lymph node involvement (pN+) were significantly associated with worse overall, cancer-specific and recurrence-free survival rates. Conclusion: We report acceptable mid-term and promising long-term oncological outcome after LRC and standard laparoscopic PLND without neoadjuvant or adjuvant therapy.

Transperitoneal laparoscopic radical nephrectomy in a patient with severe scoliosis.

OBJECTIVE To report the first case of a left transperitoneal laparoscopic nephrectomy in a patient with a severe left convex lumbar scoliosis and to elaborate on the technical difficulties of this procedure. METHODS The surgical procedure was performed by an experienced laparoscopic surgeon after rigorous pre-operative visualization of the altered visceral and vascular abdominal anatomy. A transperitoneal laparoscopic approach with an open introduction technique according to Hasson and a caudo-cranial dissection of the left renal hilum were performed to prevent major vascular and visceral injury in this challenging surgical procedure. RESULTS The operation time was 102 minutes and the estimated blood loss was 100 mL. The surgeon was able to complete the transperitoneal laparoscopic radical nephrectomy without complications. CONCLUSION Transperitoneal laparoscopic radical nephrectomy in patients with severe spinal deformities is feasible, but should only be performed by experienced laparoscopic surgeons to ensure patient safety and cancer control.

Superior efficacy of neoadjuvant chemotherapy and radical cystectomy in cT3-4aN0M0 compared to cT2N0M0 bladder cancer: Superior efficacy of neoadjuvant chemotherapy and radical cystectomy

In this study, we compared complete pathological downstaging (pCD, ≤(y)pT1N0) and overall survival (OS) in patients with cT2 versus cT3–4aN0M0 UC of the bladder undergoing radical cystectomy (RC) with or without neoadjuvant chemo‐ (NAC) or radiotherapy (NAR). A population‐based sample of 5,517 patients, who underwent upfront RC versus NAC + RC or NAR + RC for cT2‐4aN0M0 UC between 1995–2013, was identified from the Netherlands Cancer Registry. Data were retrieved from individual patient files and pathology reports. pCD‐rates were compared using Chi‐square tests and OS was estimated by Kaplan–Meier analyses. Multivariable analyses were conducted to determine odds (OR) and hazard ratios (HR) for pCD‐status and OS, respectively. We included 4,504 (82%) patients with cT2 and 1,013 (18%) with cT3–4a UC. Median follow‐up was 9.2 years. In cT2 UC, pCD‐rate was 25% after upfront RC versus 43% (p < 0.001) and 33% (p = 0.130) after NAC + RC and NAR + RC, respectively. In cT3–4a UC, pCD‐rate was 8% after upfront RC versus 37% (p < 0.001) and 16% (p = 0.281) after NAC + RC and NAR + RC, respectively. In cT2 UC, 5‐year OS was 57% and 51% for NAC + RC and upfront RC, respectively (p = 0.135), whereas in cT3–4a UC, 5‐year OS was 55% for NAC + RC versus 36% for upfront RC (p < 0.001). In multivariable analysis for OS, NAC was beneficial in cT3–4a UC (HR: 0.67, 95%CI 0.51–0.89) but not in cT2 UC (HR: 0.91, 95%CI 0.72–1.15). NAR did not influence OS. In conclusion, NAC + RC was associated with superior pCD compared to RC alone and NAR + RC. Superior OS for NAC + RC compared to RC alone was especially evident in cT3–4a disease.