DNA Ploidy as a Prognostic Factor in Renal Cell Carcinoma
DNA Ploidy as a Prognostic Factor in Renal Cell Carcinoma
Abstract & Commentary
Synopsis: Renal cell carcinoma (RCC) has an extremely variable clinical course that is only partially described by current staging and grading systems. Even in the presence of metastatic disease, some patients will have long survivals with preservation of performance status. In general, performance status and sites of metastatic disease have predicted prognosis and response to immunotherapy-based treatment regimens for stage IV disease, but the prognosis for earlier stage disease has relied heavily on tumor stage. This paper identified ploidy, carefully assessed in multiple sections of primary tumors, as a stronger independent predictor of recurrence and survival than tumor stage.
Source: Abou-Rebyeh H, et al. Cancer. 2001;92: 2280-2285.
Renal cell carcinoma is increasing in inci-dence at an annual rate of 2% worldwide and is often discovered incidentally in the absence of symptoms. One third of patients who undergo apparently curative resections will ultimately develop metastatic disease. DNA content has not previously been identified as a prognostic factor. However, these studies have been criticized because sampling methods may not have allowed for examination of all areas of the tumor. The study cited here examined 180 T1, T2, or T3 (8%, 51%, and 41% of the total, respectively) primary, nonmetastatic, fully resectable RCCs by sampling 8 different areas of the tumor for DNA ploidy. DNA content was measured in 300 tumor cell nuclei in each specimen and was defined as diploid or polyploid when it corresponded with the mean value of the standard diploid population (± 25%) or its multiple (± 25%). All cell nuclei with a DNA content outside of the diploid or polyploid ranges were termed as aneuploid. Tumors were thus classified as diploid (n = 56), polyploid (n = 20), or aneuploid (n = 104).
Of the 180 specimens, 41% were Grade I, 43% were Grade II, and 16% were Grade III. Although higher-grade tumors tended to more frequently exhibit aneuploidy, tumor grade did not reliably predict for ploidy (30%, 72%, and 100% aneuploidy for Grades I, II, and III, respectively). Ten-year survivals were available at the time of analysis and were typical for that reported elsewhere: pT1 85%, pT2 53%, and pT3 8%. However, 10-year survivals were 92%, 80%, and 0% for diploid, polyploid, and aneuploid tumors, respectively, regardless of tumor stage or grade. Univariate analysis showed that DNA ploidy, tumor stage, and tumor grade were significant predictors for tumor recurrence and progression. Multivariate analysis showed that only DNA ploidy (P < .001) and tumor stage (P = .004) were significant independent predictors of tumor progression whereas tumor grade (P = .125) was not.
Comment by Michael J. Hawkins, MD
Since there is no adjuvant therapy that is of known benefit for patients with early stage RCC, at present the need to identify patients with greater risk of eventual recurrence is not necessarily compelling. In addition, the striking results of this study—using the extensive sampling procedures described—clearly need to be confirmed. Nonetheless, the results of this study are intriguing and could have major implications in the way these patients are managed in the future. Recent studies have shown a role for nephrectomy in patients with metastatic disease-increasing survival by 50% in selected patients. One of the more difficult clinical dilemmas in treating patients with metastatic disease is when to initiate treatment. IL-2 based regimens typically are associated with profound fatigue, loss of appetite, and decreased performance status. In patients who are feeling well, it is difficult to know when to subject them to treatment and a course of close observation to identify the aggressiveness of their malignancy is often appropriate. In the future, however, it may be possible to identify those patients whose tumors are destined to follow a more aggressive course by examining the DNA content and initiating therapy earlier for patients with aneuploid tumors.
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