Primary renal neuroendocrine neoplasms: A systematic literature review, report of four local cases, and original survival analysis of 63 patients from a national registry 2012–2018

Abstract

Primary renal neuroendocrine neoplasms (NEN) are rare. We aimed to conduct a systematic review, present local cases, and analyse data from the England's National Cancer Registration and Analysis Service (NCRAS) to provide comprehensive evidence on clinical experience, incidence, and survival to better characterize these tumours. First, a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method; second, a synthesis of local cases; and, finally, a retrospective population-based cohort analysis of renal NEN recorded between 2012 and 2018 on NCRAS were performed. Kaplan-Meier estimator was used to calculate overall survival and Cox proportional hazard regression to identify prognostic factors. Systematic review identified 48 articles and the evidence was summarized and presented. We reported data from four local cases presenting with abdominal and back pain but without carcinoid syndrome. In population-based analysis, we identified 63 cases of renal NEN between 2012 and 2018 from the registry. Age-standardized incidence was 0.09-0.32 per million with a median age of 64 years (interquartile range = 48-72 years). Survival was worse in males and those aged 64 years and over. Five-year survival for renal neuroendocrine tumours (NET) was 69.8% (95% confidence interval = 66.6-72.7) and neuroendocrine carcinomas (NEC) was 38.4% (95% confidence interval = 34.6-42.0). No independent predictive factor was identified in the multivariable analyses. We have given a systematic review of evidence, published local experience, and reported incidence and survival of renal NEN in England for the first time. We have provided clinicians with evidence on diagnosis and proposed a treatment algorithm of theses rare tumours. The incidence and median age of presentation in England is similar to other published series. Renal NET has better survival than renal NEC as expected. A uniform classification system would reduce inconsistencies in reporting and standardize treatment decisions for this neoplasia.

Extrapulmonary Neuroendocrine Carcinomas: Current Management and Future Perspectives

“…Due to the very low incidence of renal NECs, little is known about their clinical characteristics, and therapeutic strategies are yet very limited. A recent comprehensive systematic review, which also put together case reports and data from England's National Cancer Registration and Analysis Service (NCRAS) registry, highlighted that renal NECs are diagnosed at a median age of 70 years (thus, in older individuals when compared with well-differentiated renal NETs), while inconsistent associations between sex and renal NENs have been found [170]. Furthermore, the primary tumors of renal NECs are larger in size than those of well-differentiated renal NETs, as about 20% of renal NECs have a tumor size greater than 10 cm, which is negatively associated with prognosis [170].…”

“…A recent comprehensive systematic review, which also put together case reports and data from England's National Cancer Registration and Analysis Service (NCRAS) registry, highlighted that renal NECs are diagnosed at a median age of 70 years (thus, in older individuals when compared with well-differentiated renal NETs), while inconsistent associations between sex and renal NENs have been found [170]. Furthermore, the primary tumors of renal NECs are larger in size than those of well-differentiated renal NETs, as about 20% of renal NECs have a tumor size greater than 10 cm, which is negatively associated with prognosis [170]. Indeed, 80% of renal NECs are metastatic at diagnosis, frequently spreading to the liver and bones, but also to the brain and lungs as reported in several case series [171].…”

“…Renal NEC does not seem to be associated with horseshoe kidney. Paraneoplastic syndromes, such as inappropriate antidiuretic hormone syndrome (SIADH), have been reported in a few cases of metastatic renal NECs [170,171]. Due to the rarity of this disease and the lack of prospective trials, no recommendations about the optimal therapeutic strategies, combined or sequential treatments, are available to date.…”

“…Due to the rarity of this disease and the lack of prospective trials, no recommendations about the optimal therapeutic strategies, combined or sequential treatments, are available to date. There is some evidence that a platinum-based chemotherapy regimen can substantially impact the survival of these patients, since a median survival of 20 months was observed in patients with renal SCNECs receiving platinum-based chemotherapy, compared to 8 months in patients receiving other chemotherapy regimens without platinum [170]. Moreover, survival analyses were conducted in 63 patients with renal NENs reported in the NCRAS between 2012-2018, confirming the aggressiveness of this disease, as the 5-year survival of renal NECs was 38.4% [170].…”

“…There is some evidence that a platinum-based chemotherapy regimen can substantially impact the survival of these patients, since a median survival of 20 months was observed in patients with renal SCNECs receiving platinum-based chemotherapy, compared to 8 months in patients receiving other chemotherapy regimens without platinum [170]. Moreover, survival analyses were conducted in 63 patients with renal NENs reported in the NCRAS between 2012-2018, confirming the aggressiveness of this disease, as the 5-year survival of renal NECs was 38.4% [170]. Registry data have shown a significant correlation between stage and prognosis, even though the prognosis of these patients remains poor in any stage, with an OS of 3 months in patients with advanced renal SCNECs and an OS of 11 months in patients with localized renal SCNECs [171].…”