The survival benefit of lymph node dissection at the time of removal of kidney, prostate and urothelial carcinomas: what is the evidence?

Introduction

Lymph node dissection (LND) has been advocated by oncologic surgeons to completely eradicate cancer. However, evidence for that strategy is solely based on poor quality data. Some randomized studies done outside the field of urology failed to show any benefit to LND. Our objective was to evaluate whether LND at the time of removal of prostate, kidney and urothelial carcinomas results in a survival benefit.

Methods

For that purpose, we performed a systematic literature review.

Results

For kidney cancer, LND might be able to cure some patients with N+ disease. In N0 patients, although a randomized trial has been completed, the value of LND remains uncertain. LND at the time of radical prostatectomy can be useful in some patients with lymph node invasion. However, studies on the impact of LND in pN0 patients are retrospective and conflictive. Extended LND has been recommended when performing a radical cystectomy based on improved outcomes observed in retrospective studies. However, these studies are limited by selection biases and results of ongoing randomized trials will specify the template and the advantages of LND when removing a bladder cancer. Recent data of large series of radical nephro-ureterectomies for upper tract urothelial carcinomas are conflicting. Some found a benefit of LND in N0 patients while others did not.

Conclusion

The studies that support LND at the time of surgery for prostate, kidney and urothelial carcinomas have low level of evidence. This should encourage urologists to design and perform well-designed randomized trials to assess the potential survival impact of a commonly done procedure.     

Prognostic role of ERCC1 protein expression in upper tract urothelial carcinoma following radical nephroureterectomy with curative intent

Background

Excision repair cross-complementing 1 (ERCC1) has been associated with outcomes of urothelial carcinoma of the bladder, but was not yet studied in upper tract urothelial carcinoma (UTUC). The aim of this study was to assess the prognostic role of ERCC1 expression in a large international cohort of UTUC patients.

Methods

Immunohistochemical ERCC1 expression was evaluated in 716 UTUC patients who underwent radical nephroureterectomy with curative intent. ERCC1 was considered positive when the H-score was >1.0. Associations with overall survival and cancer-specific survival were assessed using univariable and multivariable Cox models.

Results

ERCC1 was expressed in 303 tumors (42.3 %) and linked with the presence of tumor necrosis (16.2 vs. 10.4 %, p = 0.023), but not with any other clinical or pathological variable. ERCC1 status did not predict cancer-specific survival and overall survival on both univariable (p = 0.70 and 0.32, respectively) and multivariable analyses (p = 0.48 and 0.33, respectively).

Conclusions

ERCC1 is expressed in a significant proportion of UTUC and is linked with tumor necrosis, but its expression appears not to be associated with prognosis following radical nephroureterectomy.

     

Neoadjuvant targeted molecular therapies in patients undergoing nephrectomy and inferior vena cava thrombectomy: is it useful?

Objective

To assess the effect of neoadjuvant targeted molecular therapies (TMTs) on size and level of inferior vena cava tumor thrombi and to evaluate their impact on surgical management.

Methods

We retrospectively analyzed the data of 14 patients treated for a clear cell renal cell carcinoma with inferior vena cava thrombi by neoadjuvant TMT before nephrectomy. Clinical, pathological and perioperative data were gathered retrospectively at each institution. The primitive tumor size and the thrombus size were defined by computed tomography before TMT. The tumor thrombus level was defined according to the Novick’s classification.

Results

Before TMT, thrombus level was staged I for 1 (7 %), II for 10 (72 %) and III (21 %) for 3 patients. First-line therapy was sunitinib in 11 cases and sorafenib in 3 cases. Median therapy duration was two cycles (1–5). Three patients experienced major adverse effects (grade III) during TMT. Following TMT, 6 (43 %) patients had a measurable decrease, 6 (43 %) had no change, and 2 (14 %) had an increase in the thrombus. One patient (7 %) had a downstage of thrombus level, 12 (85 %) had stable thrombi, and 1 (7 %) had an upstage. Regarding primary tumor, 7 (50 %), 5 (36 %) and 2 (14 %) patients had a decrease, stabilization and an increase in tumor size, respectively.

Conclusion

Neoadjuvant TMT appears to have limited effects on renal tumor thrombi. This retrospective study failed to demonstrate a significant impact of neoadjuvant TMT on surgical management of clear cell renal cell carcinoma with inferior vena cava tumor thrombi.     

Predictors of Cancer-specific Mortality After Disease Recurrence in Patients with Squamous Cell Carcinoma of the Penis

Disease recurrence occurs frequently after surgical treatment for squamous cell carcinoma of the penis (SCCp). We sought to determine prognostic factors that influence cancer-specific mortality (CSM) after disease recurrence in patients with SCCp. We performed a retrospective analysis of 314 patients who experienced disease recurrence after surgical treatment for SCCp between 1949 and 2012. Competing risk regression analysis addressed factors associated with CSM after SCCp recurrence. Median time from surgery to disease recurrence was 10.5 mo (interquartile range [IQR]: 5.9–21.3). Of the recurrences, 165 (53%), 118 (38%), and 31 (9.9%) were local, regional, or distant, respectively. Within a median follow-up of 4.5 yr (IQR: 2.0–6.5), 108 patients died of SCCp and 41 patients died of causes other than SCCp. Shorter time to disease recurrence was found to be significantly associated with a higher risk of CSM (p = 0.0006). Lymph node metastasis at the time of initial treatment (subdistribution hazard ratio [SHR]: 1.96; 95% confidence interval [CI] 1.23– 3.11; p = 0.005) and regional recurrence (SHR: 4.14; 95% CI, 2.16–7.93; p < 0.0001) or distant recurrence (SHR: 5.75; 95% CI, 2.59–12.73; p < 0.0001) were associated with increased risk of CSM after disease recurrence. Inclusion of time to recurrence into risk stratification may help patient counseling and treatment planning.     

Blood- and tissue-based biomarkers for prediction of outcomes in urothelial carcinoma of the bladder

ObjectivesUrothelial carcinoma of the bladder (UCB) is a highly heterogeneous malignancy that causes significant morbidity and mortality. Standard pathologic features (stage, grade, and nodal status) are insufficient to predict accurately a patient's outcome. Biomarkers could help clinicians provide individualized prognostications and allow risk-stratified clinical decision making regarding surgical and medical treatment. This review summarizes the existing tissue- and blood-based biomarkers in UCB.Material and methodsA PubMed/Medline search was conducted to identify original articles regarding molecular biomarkers and UCB. Searches were limited to papers published in English. Keywords included urothelial carcinoma, bladder cancer, transitional cell, biomarker, marker, staining, cystectomy, recurrence or progression, survival, prediction, and prognosis.ResultsThe articles with the highest level of evidence were selected and reviewed, with the consensus of all the authors of this paper.ConclusionsThere is no doubt that a panel of biomarkers would eventually improve our clinical decision making regarding treatment and follow-up. However, to date, no biomarker panel is yet validated for daily clinical practice.