The incidence of renal cell carcinoma (RCC) is higher in patients with end-stage renal disease (ESRD), with a relatively recent study reporting a standardized incidence ratio (SIR) of 4.03 (95% CI, 3.88-4.19).1 The underlying pathophysiology to explain this increased incidence is likely multifactorial and includes increased oxidative stress, impaired immunity, excess free radicals, and reduced DNA repair.2 Patients undergoing hemodialysis (HD) may develop different variations of RCC, including bilateral, multicentric and non–clear cell tumors.3

There are currently mixed data regarding the clinical outcomes of patients with RCC who are concomitantly on HD, with some reports indicating a better prognosis based on an earlier diagnosis being made.4,5 In contrast, other studies have shown no differences in cancer-specific survival (CSS) when comparing patients with RCC on HD to those not receiving HD.6 Recently, a group led by Hayami et al conducted a retrospective study to further investigate the prognostic role of HD in patients with RCC and published their findings in Seminars in Dialysis.3

The authors performed a retrospective chart review of 388 patients who underwent a radical or partial nephrectomy for RCC at a single hospital in Japan from 2005 to 2013. In it, they found that 66 of 388 (17%) of patients were found to be on HD, of which the median duration of dialysis was 168 months. The most common causes of ESRD on HD were chronic glomerulonephritis (59%), autosomal dominant polycystic kidney disease (20%), diabetic nephropathy (8%), and miscellaneous causes (17%). Forty-one percent of the patients on HD had multicentric tumors with different histologic types. 

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When comparing the HD and non-HD groups, there were no significant differences between sex and age of patients at surgery. An incidental diagnosis was made more frequently in the non-HD group compared with the HD group (78% vs 65%, P =.014). HD patients had a shorter follow-up compared with non-HD patients (42.5 months vs 54.5 months, P =.021).

With respect to histologic subtype, clear cell was the most common in both groups, however, it was significantly higher in the non-HD vs HD group (89% vs 53%, P <.001). Papillary, clear cell papillary, and acquired cystic disease (ACD)-associated subtypes were all significantly more common in the HD group. Patients in the HD group were more likely to be classified as TNM stage I compared with the non-HD group (86% vs 74%, P =.045). Similarly, patients in the HD group were significantly more likely to have Fuhrman nuclear grade 3 and 4 compared with non-HD patients. In general, patients on HD were more likely to have smaller (median 3 cm vs 4 cm, P =.002), multicentric (41% vs 1.2%, P <.001), and bilateral tumors (14% vs 0.6%, P <.001). More patients in the HD group were found to have a sarcomatoid component (11% vs 3%, P =.002).

When evaluating clinical outcomes, patients in the HD group had a significantly worse 5-year CSS compared with non-HD: 82.8% vs 93.5% (P =.02). Similarly, HD was also associated with significantly lower overall survival (OS), although the specific percentages were not provided from the Kaplan-Meier analysis and curves.

Multivariate analyses indicated that HD (hazard ratio [HR], 5.11; P =.002), stage (HR, 7.50-125; P <.025) and Fuhrman nuclear grade 4 (HR, 26; P =.002) were independent prognostic factors for RCC CSS. Univariate analysis also found HD to be an independent prognostic factor for CSS, albeit at a lower HR (2.34, P =.024). Outside of death from RCC itself, the most common causes of death in patients on HD included cardiovascular events (myocardial infarctions, strokes, and sudden cardiac death), infections and malignancy other than RCC.

The authors concluded that patients with RCC who are on HD had a worse prognosis compared with those not receiving HD. These findings are in contrast to some prior studies, including a study published by Neuzillet et al that evaluated a total of 1250 patients with RCC (303 HD, 947 non-HD) from 24 university departments in France.7 In this study, the univariate analysis found that ESRD was a favorable prognostic factor, while multivariate analysis did not show any significance.

Hayami et al explained that their findings may be due to the high 5-year CSS rates in the patients not getting HD, which may be at least partially attributable to higher rates of incidental diagnosis. These high rates of incidental diagnosis can also be a byproduct of the Japan’s national health insurance system. In contrast, the 5-year CSS rates for those patients on HD were lower when compared with prior studies.6,7 The authors attributed this to the long duration of HD with a median time of 168 months along with higher incidence of several of the more aggressive subtypes of RCC (ACD-associated, sarcomatoid component, and Fuhrman grade 3/4). In addition, the authors also believed it was reasonable to attribute worse outcomes in the HD group to the complex underlying pathophysiology, including reduced immunity and excess free radicals. These processes may directly impact the development and worsening of RCC, as well as provide a nidus for pathophysiologic states to arise, especially in the cardiovascular and oncologic realm.

This study was limited by several factors, including its retrospective nature and limited patient population, especially in the HD group. The data were taken only from 1 center in a single country. It will be interesting to evaluate the impact of HD on RCC outcomes in future studies, especially those that incorporate multiple centers from different countries.

References

  1. Butler AM, Olshan AF, Kshirsagar AV, et al. Cancer incidence among US Medicare ESRD patients receiving hemodialysis, 1996-2009. Am J Kidney Dis. 2015;65(5):763–772. doi:10.1053/j.ajkd.2014.12.013
  2. Petrolla AA, Maclennan GT. Renal cell carcinoma associated with end stage renal disease. J Urol. 2006;176(1):345. doi:10.1016/j.juro.2006.04.007
  3. Hayami N, Ubara Y, Okaneya T, et al. Outcome of renal cell carcinoma in patients on dialysis compared to non-dialysis patients. Semin Dial. 2020;33(4):316-321. doi:10.1111/sdi.12888.
  4. Satoh S, Tsuchiya N, Habuchi T, et al. Renal cell and transitional cell carcinoma in a Japanese population undergoing maintenance dialysis. J Urol. 2005;174(5):1749-1753. doi:10.1097/01.ju.0000177489.98031.54
  5. Kojima Y, Takahara S, Miyake O, Nonomura N, Morimoto A, Mori H. Renal cell carcinoma in dialysis patients: a single center experience. Int J Urol. 2006;13(8):1045-1048. doi:10.1111/j.1442-2042.2006.01498.x
  6. Hashimoto Y, Takagi T, Kondo T, et al. Comparison of prognosis between patients with renal cell carcinoma (RCC) on hemodialysis and those with renal cell carcinoma in the general population. Int J Clin Oncol. 2015;20(5):1035-1041. doi:10.1007/s10147-015-0812-9
  7. Neuzillet Y, Tillou X, Mathieu R, et al. Renal cell carcinoma (RCC) in patients with end-stage renal disease exhibits many favourable clinical, pathologic, and outcome features compared with RCC in the general population. Eur Urol. 2011;60(2):366-373. doi:10.1016/j.eururo.2011.02.035

This article originally appeared on Cancer Therapy Advisor

Topics:

Kidney Cancer Renal Cell Carcinoma