To date, there is no reliable and effective treatment protocol for tRCC. Currently, the principal treatment for RCC in the pediatric population is tumor resection either with partial or radical nephrectomy [42]. Although tRCCs have been more commonly associated with the pediatric population, there is no consensus on whether the treatment regimen and surveillance protocol should be altered. Children with RCC and regional lymph node involvement demonstrate improved cancer-specific and all-cause mortality as well as higher cancer-free survival than adults diagnosed at the same stage [42].

Even with more common RCC subtypes, there is still debate and controversy regarding usefulness and reliability of renal biopsy and radiographic criteria for concerning renal lesions (Fig. 7.6 ) [43]. This lack of consensus and histological criteria leads to misdiagnosis of tRCC as well as creating confusion as to treatment response. The best treatment outcomes involve protocols that recommend radical nephrectomy and lymph node dissection prior to distant metastases [44, 45]. Hung et al. reviewed eight cases of Xp11 tRCC treated at their institution from 2007 to 2010 [45]. They concluded that the factor that directly effects patient survival is the presence of distant metastases at the time of diagnosis or at the time of surgery. Of the four patients who presented with stage I or II disease at the time of nephrectomy, three were disease-free at 24, 16, and 2 months postoperatively. With such a limited number of cohorts, any conclusive recommendation is difficult in regard to advantage of radical versus partial nephrectomy and/or the impact of an extended lymph node dissection.

In general, tRCC response to standard immunotherapy or chemotherapy is poor, and patients have a relatively short overall survival [27]. Modest results have been reported with the receptor tyrosine kinase inhibitor sunitinib [46, 47]. In a 2010 study, Malouf et al. examined 21 adult patients with Xp11 tRCC and metastatic disease that had received targeted anti-VEGF or mTOR inhibitors [47]. They observed an 8.2-month progression-free survival in the sunitinib group compared with 2-month progression-free survival observed in the group receiving cytokine therapy. A retrospective review of 15 adult patients (12 females; median age 40 years) with tRCC who were treated with targeted therapy at four centers in the United States showed an overall response rate of 20 %, with median progression-free survival of 7.1 months and median overall survival of 14.3 months [36, 48]. A Children’s Oncology Group (COG ) clinical trial is currently testing the effectiveness of antiangiogenesis agents comparing Xp11 tRCC with adult RCC [49]. A second current trial with tivantinib (agent ARQ 197) for the treatment of tRCCs showed limited effectiveness [50]; however, this is an area of continued clinical research. Although ultimately fatal, targeted therapy with both temsirolimus and sunitinib appears to be the optimal management of metastatic Xp11 tRCC [27, 46, 47].

t(6;11) tRCC has been described as having an indolent pathologic course [37]. Among the patients with t(6;11) tRCC who have documented outcomes, the majority are treated with radical nephrectomy and present with localized disease [19, 20, 37, 51–57]. However, until long-term clinical outcomes are available, a potential aggressive clinical course for patients with t(3;6) tRCC should not be underestimated as they may require assertive treatment and follow-up.

Due to the aggressive nature and advanced-stage presentation of Xp11 tumors, the effectiveness of metastasectomy has been brought into question. Although the usefulness and feasibility of metastasectomy in advanced Xp11 tRCC has not been established, studies have reported successful results performing metastasectomy for patients with limited metastatic disease and with histopathologic variants similar to prototypical RCC [58–60]. In general, as with typical RCC, isolated pulmonary metastases are lesions most amenable to metastasectomy, with median 5-year survival rates of 35–50 % [58–60]. Kavolius et al. reported a series of 278 patients with recurrent RCC, of whom 141 (50.7 %) underwent curative metastasectomy and 70 (25.2 %) underwent noncurative metastasectomy [59]. Multivariate analysis identified a solitary metastatic lesion, age <60 years, and disease-free survival of >12 months as favorable prognostic factors [59]. These findings, along with tRCC’s relative lack of sensitivity to current chemotherapeutic and radiotherapeutic agents , add evidence albeit weak, to the prospect of utilizing metastasectomy in the treatment protocol of patients with metastatic Xp11 tRCC.

As with diagnosis and treatment, there is currently no proven, reliable, or effective surveillance algorithm for tRCC for patients after radical nephrectomy . However, in 2006, Chin et al. developed and proposed a novel staging system for RCC that incorporated the 1997 TNM classification with the Eastern Cooperative Oncology Group performance status and Fuhrman grade (UCLA Integrated Staging System) into a single prognostic algorithm [61]. They recommended treatment follow-up according to stratification into low-, intermediate-, or high-risk categories . Because Xp11 tRCC has an unpredictable and aggressive disease course, it is reasonable to stratify patients with Xp11 tRCC as high risk and place them into the proposed post-nephrectomy surveillance algorithm developed by Chin et al. Their protocol recommends (a) history, physical examinations, and laboratory tests every 6 months for 3 years and then yearly until 10 years; (b) chest computed tomography every 6 months for 3 years and then yearly until 10 years (chest computed tomography alternating with chest radiography after 3 years); and (c) abdominal computed tomography every 6 months for 2 years, yearly until 5 years, and then every 2 years until 10 years [61]. In addition to their recommendations, because Xp11 tRCC is often diagnosed in young adults, it may be reasonable to suggest lifelong surveillance with yearly history, physical examination, and laboratory tests and chest and/or abdominal imaging, as deemed clinically necessary, after completing the previously described 10-year surveillance regimen (Table 7.1 ) [62]. The rarity of t(6;11) tRCC and chromosomal 3 tRCCs does not enable definitive recommendations regarding a surveillance protocol after treatment. At this point, it seems reasonable to recommend the same surveillance protocol as with Xp11 tRCC until further clinical outcomes are reported.