The Behavior of Renal Cell Carcinoma: Sex, Lies and Tumor Size

The size of renal cell carcinoma has frequently been associated with prognosis. In this issue of The Journal Klatte et al (page 1719) report on 1,208 patients with tumors 4.0 cm or smaller who were treated with nephrectomy at 5 international centers. Of the tumors 88% were renal cell carcinoma. Interestingly the incidence of metastatic disease was found to be similar in 1, 2 and 3 cm tumors, and 3% of patients with initial localized disease died of renal cell carcinoma. As new forms of less invasive treatment for renal tumors such as radio frequency ablation and cryotherapy emerge, the natural history of these small tumors remains important. Factors associated with metastatic disease included poor performance status, symptoms, higher T stage and higher grade. It was interesting that patients who presented with metastatic disease had a median survival time of 45 months. One and 5-year survival rates were 76% and 42%, respectively, which are considerably better than expected in patients with renal cell carcinoma with larger tumors. There were some limitations to this study including a lack of pathological review by a single pathologist. How often was there peripelvic fat involvement or microvascular invasion? There was no standardization of preoperative imaging or postoperative surveillance. How many patients had formal nodal dissections and how many did not? How often was there careful pathological review of regional lymph nodes? In spite of some of these deficiencies it is apparent that small renal tumors, even in the 1 to 2 cm range, have a small but real risk of metastasis. In a study of sex differences in renal cell carcinoma and variances of survival, Woldrich et al (page 1709) found that there was a male prevalence of 62%. Women had a higher incidence of stage I tumors (54%) but were 1 year older at a mean age of 64 vs 63 years. There was a trend toward increased survival in women. Women may be more likely to have imaging and obtain medical care more often than males, although the males in this study were 1 year younger. In addition, women may have less comorbidity than males of the same age. In a study by Stafford et al (page 1704) on racial, ethnic and gender disparities in renal cell carcinoma, 39,434 cases of renal cell carcinoma from the California Cancer Registry were reviewed during a 6-year period. An increased incidence of renal cell carcinoma was found. Black patients had a higher incidence and a lower survival rate than all other races and ethnicities despite having more localized cancer. Black patients were also diagnosed at a younger age than their counterparts. Males had twice the incidence of females as well as a lower survival rate. Asians and Pacific Islanders appeared to have the opposite findings of a lower incidence of renal cancer and higher survival rate. Racial, ethnic and gender disparities in renal cell carcinoma may be associated with different survival. These 3 articles demonstrate significant variability in renal cell carcinoma. Some of the observations have been made previously, particularly that of increased incidence in males. Biological behaviors and environmental factors may potentially affect these tumors in different populations. Although it is helpful to review large populations of patients with renal cell carcinoma and determine increased trends in the occurrence of this disease, other methods of study are needed. There are many nomograms from different institutions that describe prognostic clinical features. The next step is adding molecular characterization. The molecular diagnosis of renal cell carcinoma is becoming established. 1 What are the molecular markers that will help define risk? When these molecular markers are incorporated into a clinical nomogram then greater diagnostic and prognostic accuracy will occur. In addition, higher risk patients may be treated quite differently in the future. For example, radio frequency ablation, cryotherapy or watchful waiting might be considered in low risk patients. Adjuvant therapy in the form of tumor vaccines, antiangiogenesis agents or other forms of treatment might be considered in high risk patients.