Cytoreductive nephrectomy in metastatic papillary renal cell carcinoma

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Published: 9 Feb 2018
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Dr Jeffrey Graham - Tom Baker Cancer Centre, Calgary, Canada

Dr Graham speaks with ecancer at the 2018 ASCO Genitourinary Cancers Symposium about a retrospective analysis of patients with papillary metastatic renal cell carcinoma treated with or without cytoreductive nephrectomy. 

He highlights that the use of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma and papillary histology appears to be associated with improved survival when compared to no cytoreductive nephrectomy after adjustment for risk criteria.

Our abstract is titled 'Cytoreductive nephrectomy in papillary metastatic renal cell carcinoma: results from the IMDC.' Basically there's evidence that removing the primary tumour in the setting of metastatic renal cell carcinoma is associated with an improvement in survival. This is based on prospective data in the interferon era as well as retrospective analyses in the more modern targeted therapy era. The majority of these studies have focussed on clear cell renal cell carcinoma which is the most common subtype of renal cell carcinoma; there is less information on non-clear cell renal cell carcinoma. Of non-clear cell renal cell carcinoma the most popular subtype, the most prevalent subtype, is papillary renal cell carcinoma. There's evidence to suggest that, compared to clear cell, papillary renal cell carcinoma has distinct biological and clinical characteristics and given that background the aim of our study was to analyse the role of cytoreductive nephrectomy in papillary metastatic renal cell carcinoma.

Basically the definition of a cytoreductive nephrectomy is surgically resecting the primary renal tumour in the setting of metastatic disease. That's distinct from a nephrectomy done prior to the development of metastatic disease. So, for instance, a patient who had a nephrectomy two years in the past and then develops metastatic disease as opposed to having metastatic disease develop synchronously with the primary renal tumour.

Essentially we analysed the IMDC, which is the International Metastatic Renal Cell Database Consortium. It's a multi-institutional database that includes metastatic renal cell carcinoma patients. It currently has just under 9,000 patients and around 38 institutions contribute information to it. We collect data on a number of biological and clinical variables for each patient. So, using that database we retrospectively identified patients with papillary histology and then of those we identified those who had a cytoreductive nephrectomy and those who did not. We actually excluded those who had a nephrectomy prior to the diagnosis of metastatic disease, thus isolating those with a synchronous metastatic disease. So our final numbers were 109 patients were identified as not having a nephrectomy and around 244 patients had a cytoreductive nephrectomy. Those represented our final numbers in our analysis.

Basically we compared outcomes between those two groups, including progression free survival and overall survival and we performed multivariable regression analysis controlling for inherent prognostic imbalances between those two groups. The factors that we controlled for were the IMDC risk factors and those include a low haemoglobin, an elevated neutrophil count, an elevated corrected calcium, an elevated platelet count as well as a poor performance status and a diagnosis to treatment interval of less than one year. So those variables were controlled for in order to come up with our final hazard ratios.

Our findings suggest that in the setting of metastatic papillary renal cell carcinoma that a cytoreductive nephrectomy does appear to offer a survival benefit. The median overall survival was almost doubled in the group receiving the surgical resection and when controlling for the previously mentioned prognostic factors the hazard ratio was 0.62, suggesting that even when controlling for inherent prognostic imbalances between the two groups that there does appear to be a survival advantage with cytoreductive nephrectomy in papillary renal cell carcinoma.

What is the take home message?

I think the take home points of this are that, similar to the clear cell literature, that a number of different databases have suggested that there is a signal that cytoreductive nephrectomy does appear to be associated with a survival benefit. Our study is, to our knowledge, the largest looking at exclusively papillary histology and the findings are similar to the clear cell population. So our clinical take home points would be that in clinical practice patients who have papillary histology and develop or present with synchronous metastatic disease, that a cytoreductive nephrectomy may offer them a survival benefit. The important point to note is that due to the rarity of this subgroup a prospective clinical trial may not be feasible in the future given the low patient numbers globally of this subtype thus leaving these retrospective analyses the best evidence we have for this procedure.