Prognostic variables in adult Wilms tumour

Discussion

In the past, adults with Wilms tumour have been treated with therapeutic protocols based on data derived from pediatric NWTS data. However, owing to small numbers in each of the adult Wilms tumour case series, it is not clear whether the prognosis of adult Wilms tumour is comparable to that for pediatric Wilms tumour. We believe that our study adds novel data showing the prognosis to be significantly worse in cases of adult Wilms tumour. In pediatric patients studied in NWTS III, D’Angio and colleagues24 showed that the risk of relapse from FH Wilms tumour is low, at about 10% for stage I–II tumours and 20% for stage III–IV tumours. Conversely, all UH tumours had inferior prognosis, compared with FH tumours, regardless of stage (36%–45% 5-year survival). In our study, overall patient survival was only 65% in patients with FH and 37% in patients with UH. Because we only reviewed studies that treated patients with adult Wilms tumour according to pediatric NWTS protocols, it is not clear why overall results in adult Wilms tumour appear to be inferior when compared with pediatric Wilms tumour, despite stage-and histology-based comparisons.

It is possible that our results are biased by diagnostic error. Adult Wilms tumour might have been wrongly diagnosed in several of the series that we used for our analysis. Indeed, some of these patients may have had sarcoma and not Wilms tumour. However, there are some important trends that must be highlighted. As in the pediatric NWTS results, for FH tumours, the prognoses for stage I and II tumours were not different, and similarly, the prognoses for stage III and IV tumours were identical. As well, among adult Wilms tumour patients with UH, there was a marked reduction in survival, compared with survival rates seen in the FH group. Again, this is in keeping with prognostic trends seen in the pediatric NWTS results. Nevertheless, we recommend that histology from patients with presumed adult Wilms tumour be sent to the NWTS for confirmation of diagnosis.

In addition to the potential difficulties of differentiating adult Wilms tumour from sarcoma, the diagnosis of anaplasia and staging can be difficult. 22 The tumour must be sampled well as small foci of anaplasia can be associated with a poor response to therapy.21 Extensive gross sectioning and good histologic preparations, fixations, sectioning and staining are absolutely required to recognize anaplasia, and thus UH, correctly.22 Most Wilms tumour with anaplasia occurs in older children and adults, and any anaplasia present, identified or unidentified, results in significantly poorer survival outcomes. Staging challenges arise because the tumours usually distort the renal pelvis, hilar structures and renal capsule. Thus, differentiating between stage I and II tumours can be extremely difficult.22

The poor results for adult Wilms tumour may also be due to the adult oncologist’s lack of familiarity with this disease. In fact, as an offshoot of the NWTS, Kalapurakal and colleagues10 reviewed 23 patients with FH adult Wilms tumour. Their overall 5-year survival rate was excellent (83%) and suggested that therapy in adults with FH should be directed according to pediatric NWTS protocols. 10 The patients analyzed in our study were treated between 1973 and 2006, and treatment protocol varied depending on the NWTS recommendations at the time. Conversely, the adults treated in the Kalapurakal study were treated by contemporary NWTS IV and V protocols, and the excellent results may reflect improvements in diagnostic testing and therapy. Nevertheless, we believe that it is important to include the input of pediatric oncologists in the treatment of adults with Wilms tumour.

Even with a collaborative approach between pediatric and adult oncologists, there will be challenges in adapting pediatric chemotherapy treatment dosages to adults because of the toxicity of these high dosages. However, the use of hemopoietic growth factors to allow dosage escalation and to decrease the toxicity of systemic chemotherapy may be considered for certain patients at high risk for treatment failure with the recommended NWTS IV and V protocols.

The extent of surgical excision including the regional lymph nodes may also be a factor in survival outcomes. Regional lymph node dissection (LND) is not routinely performed in adult patients with Wilms tumour. One of the 6 patients studied from our Canadian centres did have a recurrence in a regional lymph node requiring re-exploration and regional LND. In adult patients with Wilms tumour, many of the tumours are large and locally advanced at the time of diagnosis. Routine regional LND may improve local recurrence rates and survival. Although this is controversial in renal cell carcinoma, Wilms tumour does have different biology, and routine regional LND has provided survival benefits in other malignancies.25 It is also important to note that, in adults, the diagnosis of Wilms tumour is never made before such therapeutic intervention as radical nephrectomy and lymphadenectomy. Thus patients may not benefit from preemptive chemotherapy, and intervention may be performed outside the state-of-the-art recommendations.

An alternative explanation for the different results in our study may be the heterogeneity in the biology of adult Wilms tumour. In children, Wilms tumour usually presents as an asymptomatic abdominal mass. However, in adults, most patients have a constellation of symptoms that can include flank pain, weight loss or a decline in their performance status.19 This may be secondary to a higher rate of clinically occult metastases. Heterogeneity in biological behaviour also exists in Wilms tumours, whether FH or UH or within the same stage of disease. In addition to the histologic and stage-based prognostic factors used to determine therapies, methods to further define the natural history of a tumour or the response to therapy for individual Wilms tumours will be required. Molecular and genetic studies such as aspiration cytology and cytogenetic analyses of Wilms tumours26 will be necessary to gain further insight into the biology of individual tumours and may provide a means by which to improve outcomes with therapy that is more aggressively patient- and tumour-specific.