The management of BSRT presents several challenges. Radiographic imaging modalities cannot differentiate between benign and malignant renal pathology. Additionally, pathologic assessment of renal tumors via percutaneous biopsy or fine needle aspiration is often limited by insufficient sampling, false negatives, the inability to establish pathologic data regarding perirenal fat and vascular invasion, and difficulty differentiating oncocytic type neoplasms.10-18
As a result, surgical intervention remains the primary treatment for enhancing renal masses. However, in patients presenting with BSRT, other issues must be addressed including the need for complex nephron sparing surgery, staged procedures, prognosis, decline in renal function, the prospect of progressive renal insufficiency, hyperfiltration injury, and the need for future renal replacement therapy. With these issues in mind, concordance of malignancy, histologic subtype, nuclear grade, and pathologic stage may have a significant impact on treatment algorithms and disease specific prognosis.
Prior single institutional retrospective series have demonstrated high concordance rates of malignant disease in patients presenting with bilateral sporadic renal tumors. Patel et al, reviewed their experience with 46 patients with bilateral sporadic renal tumors.2
The observed incidence of bilateral tumors in their dataset was 4.25%. Of the patients with a pathologically confirmed renal malignancy, a 95% concordance rate of contralateral malignant disease was noted. While those patients with benign disease in one renal unit exhibited a 60% benign concordance rate in the contralateral kidney. However, this series did include 13 patients with asynchronous tumors. The largest series to date by Blute et al included 94 patients with BSRT. The observed concordance rate of malignant disease was 84% if RCC. While the concordance rate of bilateral benign disease was 39%. When data from these series are analyzed with FCCC and SEER data demonstrating a malignant concordance rate >95%, it suggests that the finding of malignant pathology in one kidney strongly predicts the occurrence of malignancy in the contralateral kidney. Additionally, the finding of benign disease is a poor predictor of benign disease in the contralateral kidney.
Concordance rates for histologic subtype were 89% in our institutional series, which is consistent with the 93% histologic concordance rate noted in the SEER database. These rates are slightly greater compared to the 76% histologic concordance rate noted by Patel et al. The most common histologic subtype identified bilaterally in all series was conventional clear cell RCC. Discordant histology can impact prognosis and is important when discussing pathology with patients with synchronous disease.22
This high rate of histologic subtype concordance seems logical as we learn more about the molecular pathways involved in the transformation of renal epithelia.23
Prior reports have failed to document concordance rates of nuclear grade which is an important pathologic prognostic variable in RCC. The concordance rates for nuclear grade and pathologic stage were 79% and 58% respectively in our institutional series and nuclear grade concordance was 85% in the SEER data. A recent retrospective review of 629 patients with RCC revealed 5 year disease free survival for nuclear grade as 87%, 71%, 46%, and 15% for nuclear grades G1-G4.24
Similar findings were seen in several other published series concluding nuclear grade impacts prognosis and patient outcome.25-27
Furthermore, these studies also revealed that pathologic stage asserts itself as an independent predictor of disease specific survival. Ficarra et al. report a dramatic difference in five and ten year disease specific survival based on TNM stage: 94% and 92% in stage I, 90% and 78% in stage II, 63% and 46% in stage III, and 28% and 16% in stage IV. 28
Discordant pathologic stage and grade can have significant effects on prognosis and 10 year cancer specific survival, since outcomes are likely determined by tumor with the worst prognostic features. Several studies have reported on the survival outcomes of unilateral versus bilateral tumors. A recent study demonstrated that the cancer specific survival outcome in patients with BSRT was similar to survival outcomes in patients with unilateral disease.5,29
Of note, the investigators found a small increase in local tumor recurrence and demonstrated that selected bilateral tumors can be safely approached at a single surgical procedure. However, Novick et al report a statistically significantly decreased five-year survival rate in patients with bilateral disease compared to patients with unilateral disease.30
Of interest in that series, a significant difference in survival between synchronous and metachronous tumors was not noted.
Although series have evaluated the clinical and histologic similarities of BSRT, limited information is available on the genetic clonality of BSRT. Genetic clonality refers to two or more tumors derived from the same origin, suggesting metastatic disease. In contrast, tumors that are genetically dissimilar are considered to represent separate and genetically distinct primary tumors. Thus, genetic clonality is an important consideration when approaching patients with BSRT, as the implications of a metastatic and a distinct primary tumor differ drastically. In the available series investigating the genetic clonality of BSRT sample size is relatively small, ranging from 3-10 patients.31-33 Genetic clonality was evaluated by different methods in each series and ranged from 0-60%. Because of the limited sample size in each series and the lack of adequate follow up, it is difficult to assess the impact of genetic clonality on clinical outcomes. Future investigations involving more patients with extended follow up are needed in order to determine the true clinical importance of genetic clonality when treating patients with BSRT.
Multifocal tumors were identified in 46% of patients with bilateral sporadic tumors inour series. Multifocality was present 14% of patients bilaterally and in 32% of patients unilaterally. This represents a slightly higher overall percentage than the 22% of patients with multifocal tumors reported in the series by Patel et al. A series by Richstone et al reported the occurrence of multifocal renal tumors in 5% of all patients with RCC, and 11% of patients with synchronous BSRT.3
Additional studies have also supported the notion that the incidence of multifocal tumors appears to be greater in patients with bilateral synchronous disease than unilateral disease.3
This finding becomes important when considering nephron sparing surgery for patients with bilateral disease. Ultimately the surgeon must be cognizant of this higher incidence of multifocality when determining operative plans on these complex patients with BSRT.
There are several limitations to these current data. One important factor remains that only patients with sufficient pathologic data could be included in the study. This exclusion factor eliminates data from several important subgroups of patients with BSRT, specifically patients in active surveillance protocols and those undergoing ablative therapies with insufficient tissue for pathologic diagnosis on biopsy. Masses treated by these modalities typically represent small lesions that could possibly impact concordance data. A second limitation in this series is illustrated by a significantly lower number of patients, 29%, with available data on nuclear grade. Additionally, interobserver variability can impact nuclear grade assignment. This is definitely a limitation on data obtained from SEER, as there is not a central pathology review of these patients. Furthermore, comparisons of concordance rates between individual series must be made with caution because of the differences of populations examined and lack of centralized pathology review. Finally, further data regarding survival differences of patients with synchronous versus metachronous bilateral versus unilateral renal masses are needed.