Version May 2024
INTRODUCTION — Renal cell carcinoma (RCC) is divided into two major groups based on histology: clear cell or non-clear cell RCC (ie, RCC of variant histology). Clear cell and non-clear cell RCCs are distinguished using morphology, growth pattern, cell of origin, and, where they are known, underlying biological and clinical characteristics.
Tumor dedifferentiation can develop in any RCC, independent of histology [1]. Sarcomatoid dedifferentiation, the most common form of tumor dedifferentiation, consists of cell components that are spindled or otherwise resemble sarcoma cells [1,2]. However, sarcomatoid RCC is not classified as a distinct tumor subtype because it can be seen in any histologic subtype of RCC [1,2]. Rather, these tumors are characterized by distinct molecular and biologic characteristics, including clinical response to systemic therapies. (See "Epidemiology, pathology, and pathogenesis of renal cell carcinoma".)
This topic will review the epidemiology, pathology, clinical presentation, and management of RCC with sarcomatoid features. The management of clear cell and non-clear cell RCC histologies are discussed in detail separately.
●(See "Overview of the treatment of renal cell carcinoma".)
●(See "Systemic therapy of advanced clear cell renal carcinoma".)
●(See "The treatment of advanced non-clear cell renal carcinoma".)
EPIDEMIOLOGY — RCC with sarcomatoid dedifferentiation occurs in approximately 5 to 15 percent of all patients with RCC [3-7]. Most patients present between 54 and 63 years of age [8]. Sarcomatoid RCCs occur more commonly in males than females [8] and in patients of White ethnicity compared with those of Black or Hispanic ethnicity [9].
The prevalence of RCC with sarcomatoid features also depends on the background histology and stage of disease:
●Background histology – Among tumors with sarcomatoid dedifferentiation, a greater proportion arise in the background of clear cell RCC (70 percent), although it can also be found in non-clear cell histologies [4].
Among patients with clear cell RCC and non-clear cell histologies, sarcomatoid dedifferentiation occurs at the following frequencies [3,4,6-8]:
•Clear cell histologies – 5 to 13 percent
•Non-clear cell histologies:
-Papillary – 2 to 7 percent
-Chromophobe – 9 to 13 percent
-Unclassified – 11 to 26 percent
-Collecting duct – 29 percent
Sarcomatoid dedifferentiation is extremely rare in translocation RCCs, a subtype of non-clear cell tumors [10].
●Stage – RCC with sarcomatoid features can occur in patients presenting at all stages of disease but are more common in patients with metastatic disease. In observational series, sarcomatoid features occur in up to 15 percent of patients with metastatic RCC [4,5] and 5 to 6 percent of those with localized disease [3,7]. (See "Clinical manifestations, evaluation, and staging of renal cell carcinoma", section on 'TNM staging system'.)
PATHOLOGIC FEATURES — The pathologic features of RCC with sarcomatoid features, including histology and molecular alterations, are discussed separately. (See "Epidemiology, pathology, and pathogenesis of renal cell carcinoma", section on 'Renal cell carcinoma with sarcomatoid features'.)
CLINICAL PRESENTATION AND STAGING — Patients with sarcomatoid RCC are more likely to present with locally advanced or metastatic disease than other RCC histologies due to the aggressive nature of the disease. Most patients (approximately 90 percent) are symptomatic at presentation. The most common presenting symptoms are flank or abdominal pain, hematuria, weight loss, anorexia, fatigue, and night sweats [7,8,11].
The clinical presentation and staging of sarcomatoid RCC are similar to other RCC histologies and are discussed separately. (See "Clinical manifestations, evaluation, and staging of renal cell carcinoma", section on 'Clinical manifestations'.)
TREATMENT OF LOCALIZED DISEASE — The general approach to treatment of localized (American Joint Committee on Cancer eighth edition stage I to III (table 1)) sarcomatoid RCC is surgical resection, which offers the best chance of cure. However, the presence of sarcomatoid features (as detected on intraoperative frozen section or on preoperative biopsy) often warrants more aggressive surgical treatment, including radical nephrectomy and extended lymphadenectomy. Further details on the surgical management of sarcomatoid RCC are discussed separately. (See "Definitive surgical management of renal cell carcinoma", section on 'Radical nephrectomy' and "Definitive surgical management of renal cell carcinoma", section on 'Retroperitoneal lymph nodes'.)
TREATMENT OF METASTATIC DISEASE — Approximately 50 percent or more of patients with sarcomatoid RCC present with locally advanced, unresectable or metastatic disease, compared with just 15 percent of all patients with RCC [6,7,11]. Common sites of metastatic disease in patients with sarcomatoid RCC include lungs, bone, lymph nodes, liver, and brain [8]. (See "Clinical manifestations, evaluation, and staging of renal cell carcinoma", section on 'Symptoms and signs'.)
Initial therapy (clear cell RCC with sarcomatoid features) — There are limited high-quality data on the efficacy of systemic therapies for patients with metastatic sarcomatoid RCC due to the rarity of these tumors. Most evidence is based on subgroup analyses of randomized clinical trials and observational studies. As an example, one meta-analysis of four randomized clinical trials suggested that regimens containing checkpoint inhibitor immunotherapy demonstrate exceptional clinical efficacy in those with sarcomatoid RCC [12]. By contrast, patients with sarcomatoid RCCs respond poorly to antiangiogenic or targeted therapies such as vascular endothelial growth factor receptor (VEGFR) or mechanistic target of rapamycin (mTOR) inhibitors.
Nivolumab plus ipilimumab (preferred) — For patients with treatment-naïve metastatic clear cell RCC with sarcomatoid features, we recommend nivolumab plus ipilimumab (table 2) rather than sunitinib. Nivolumab plus ipilimumab results in high complete response rates, improves long-term overall survival (OS), and offers most patients the opportunity for treatment-free survival. (See "Systemic therapy of advanced clear cell renal carcinoma", section on 'Nivolumab plus ipilimumab'.)
This combination is approved by the US Food and Drug Administration (FDA) for the initial treatment of patients with intermediate- and poor-risk metastatic clear cell RCC based on the International Metastatic RCC Database Consortium (IMDC) criteria (table 3). Most patients with sarcomatoid RCC typically present with intermediate- and poor-risk disease and thus are eligible for this therapy. We also offer this combination in patients with sarcomatoid RCC and favorable-risk disease because of the high rate of durable complete responses with this therapy, although such tumors are less common [5]. (See "Systemic therapy of advanced clear cell renal carcinoma", section on 'Nivolumab plus ipilimumab'.)
In patients with sarcomatoid tumors, the combination of nivolumab plus ipilimumab improves both OS and progression-free survival (PFS) over VEGFR inhibitor therapy based on data from a randomized phase III trial (CheckMate 214). In a post-hoc subset analysis of this study, 139 patients with intermediate- or poor-risk advanced RCC (table 3) with sarcomatoid features received either nivolumab plus ipilimumab followed by maintenance nivolumab (table 4), or sunitinib [12-15]. At a minimum follow-up of five years, relative to sunitinib, the combination of nivolumab plus ipilimumab demonstrated the following, independent of tumor programmed cell death ligand 1 (PD-L1) status [16]:
●Improved OS (five-year OS 47 versus 21 percent, median OS 49 versus 14 months, hazard ratio [HR] 0.46, 95% CI 0.29-0.71).
●Improved PFS (five-year PFS 46 versus 12 percent, median PFS 27 versus 6 months, HR 0.5, 95% CI 0.32-0.8).
●Higher objective (61 versus 23 percent) and complete (23 versus 6 percent) response rates.
●Treatment was well tolerated, with toxicity profiles similar to previously reported studies [13].
Further details regarding the administration of nivolumab plus ipilimumab, efficacy in patients with clear cell RCC based on IMDC subgroups, and expected toxicities are discussed in more detail separately. (See "Systemic therapy of advanced clear cell renal carcinoma", section on 'Nivolumab plus ipilimumab' and "Toxicities associated with immune checkpoint inhibitors".)
Nivolumab plus cabozantinib — In patients with treatment-naïve metastatic sarcomatoid RCC, nivolumab plus cabozantinib is an alternative to nivolumab plus ipilimumab. Although nivolumab plus cabozantinib improved OS over single-agent sunitinib in this population [17], longer follow-up is necessary to confirm these outcomes.
The efficacy of nivolumab plus cabozantinib over single-agent sunitinib was established in a randomized phase III trial (CheckMate 9ER) conducted in patients with treatment-naïve advanced clear cell RCC. Further details on this trial are discussed separately.(See "Systemic therapy of advanced clear cell renal carcinoma", section on 'Nivolumab plus cabozantinib'.)
At median follow-up of 18 months, in preliminary results from the subset of 75 patients with sarcomatoid features, nivolumab plus cabozantinib improved PFS (median 11 versus 4 months, HR 0.39, 95% CI 0.22-0.7), OS (median not reached versus 20 months, HR 0.36, 95% CI 0.16-0.82), and objective response rates (ORR; 56 versus 22 percent) relative to sunitinib [17].
Pembrolizumab plus axitinib — In patients with treatment-naïve metastatic sarcomatoid RCC, pembrolizumab (table 5) plus axitinib is an alternative to nivolumab plus ipilimumab. However, an OS advantage has not been established in this population.
The efficacy of pembrolizumab plus axitinib over single-agent sunitinib was established in a randomized phase III trial (KEYNOTE-426) conducted in patients with treatment-naïve advanced clear cell RCC. Further details of this trial are discussed separately. (See "Systemic therapy of advanced clear cell renal carcinoma", section on 'Pembrolizumab plus axitinib'.)
At median follow-up of 13 months, in preliminary results from a subset of 105 patients with advanced RCC with sarcomatoid features, pembrolizumab plus axitinib improved ORR (59 versus 32 percent) and complete response rates (12 versus 0 percent) relative to sunitinib [18]. While survival data are immature for those with advanced RCC with sarcomatoid features, there was a nonstatistically significant trend towards improved OS and PFS, which would be clinically meaningful if true (one-year OS 83 versus 80 percent, HR 0.58, 95% CI 0.21-1.59; one-year PFS 57 versus 26 percent, HR 0.54, 95% CI 0.29-1.00).
Lenvatinib plus pembrolizumab — In patients with treatment-naïve metastatic sarcomatoid RCC, lenvatinib plus pembrolizumab is an alternative to nivolumab plus ipilimumab. However, an OS advantage has not been established in this population.
The efficacy of lenvatinib plus pembrolizumab over single-agent sunitinib was established a randomized phase III trial (CLEAR) conducted in patients with treatment-naïve metastatic clear cell RCC. Further details of this trial are discussed separately. (See "Systemic therapy of advanced clear cell renal carcinoma", section on 'Lenvatinib plus pembrolizumab'.)
At median follow-up of 27 months, in preliminary results from the subset of 49 patients with sarcomatoid features, lenvatinib plus pembrolizumab improved PFS (median PFS 11 versus 6 months, HR 0.39, 95% CI 0.18-0.84) and ORR (61 versus 24 percent) relative to sunitinib. OS was similar between the two treatment arms (median OS NE versus NE months, HR 0.91, 95% CI 0.32-2.58) [19].
Avelumab plus axitinib — In patients with treatment-naïve metastatic RCC, the combination of avelumab plus axitinib is an appropriate alternative to nivolumab plus ipilimumab. However, an OS advantage has not been established in this population.
Avelumab plus axitinib was compared with single-agent sunitinib in a randomized phase III trial (JAVELIN RENAL 101). Further details of this study are discussed separately. (See "Systemic therapy of advanced clear cell renal carcinoma", section on 'Avelumab plus axitinib'.)
At a median follow-up of approximately 12 months, in preliminary results from the subset of 108 patients with sarcomatoid RCC, avelumab plus axitinib improved PFS (median PFS 7 versus 4 months; HR 0.57, 95% CI 0.33-1.00), objective (47 versus 21 percent), and complete (4 versus 0 percent) response rates. OS data were not reported for the sarcomatoid subgroup [20].
Less preferred regimens — Other less preferred immunotherapy options for patients with metastatic sarcomatoid RCC include atezolizumab plus bevacizumab, pembrolizumab (table 5), or nivolumab (table 4).
Atezolizumab plus bevacizumab — The combination of atezolizumab plus bevacizumab is also active in those with sarcomatoid RCC [21]. However, this combination does not have regulatory approval as initial therapy for advanced RCC, and its use remains investigational.
Further details on atezolizumab plus bevacizumab for the treatment-naïve metastatic clear cell RCC are discussed separately. (See "Systemic therapy of advanced clear cell renal carcinoma", section on 'Atezolizumab plus bevacizumab'.)
Pembrolizumab — Single-agent pembrolizumab (table 5) has clinical efficacy in metastatic clear cell RCC with sarcomatoid features, but its use remains investigational.
The efficacy of single-agent pembrolizumab (table 5) in sarcomatoid RCC was demonstrated in an open-label, nonrandomized phase II trial (KEYNOTE-427) consisting of two cohorts. Cohort A had 110 patients with treatment-naïve clear cell RCC, including 11 patients (10 percent) with sarcomatoid features [22], and cohort B had 165 patients with non-clear cell RCC, including 38 (23 percent) with sarcomatoid features [23].
At median follow-up of 36 months, in the cohort A subset, the objective and complete response rates for pembrolizumab in those with sarcomatoid RCC were 64 and 0 percent, respectively (versus 42 and 8 percent for cohort B). Further results for cohort B are discussed separately. (See 'Pembrolizumab' below.)
Further details from this study on the efficacy of pembrolizumab in advanced clear cell RCC are discussed separately. (See "Systemic therapy of advanced clear cell renal carcinoma", section on 'Pembrolizumab'.)
Initial therapy (non-clear cell RCC with sarcomatoid features)
Nivolumab plus ipilimumab — For patients with treatment-naïve non-clear cell RCC with sarcomatoid features, we suggest nivolumab plus ipilimumab rather than VEGFR inhibitors or lenvatinib plus pembrolizumab, based on observational studies [24] and extrapolating from data in clear cell RCC with sarcomatoid features. (See 'Nivolumab plus ipilimumab (preferred)' above.)
Sarcomatoid dedifferentiation can occur on a background of non-clear cell (or variant) histology RCC, including papillary, chromophobe, collecting duct, and translocation RCC. (See 'Epidemiology' above.)
In patients with non-clear cell RCC and sarcomatoid features, studies suggest that immunotherapy-based regimens are associated with improved OS relative to VEGFR inhibitors, although high-quality data are limited. As an example, one observational study evaluated initial therapy with immunotherapy-based regimens (including nivolumab plus ipilimumab) versus VEGFR inhibitors (sunitinib or pazopanib) in 103 patients with non-clear cell RCC and a sarcomatoid and/or rhabdoid component and 429 patients with non-clear cell RCC lacking a sarcomatoid and/or rhabdoid component [24]. Approximately 70 percent of the patients received nivolumab plus ipilimumab, and 30 percent received immunotherapy plus VEGFR inhibitors.
●In preliminary results for patients with sarcomatoid and/or rhabdoid non-clear cell RCC, relative to VEGFR inhibitors, immunotherapy-based regimens were associated with improved OS (median not reached versus 7 months, HR 0.25, 95% CI 0.13-0.49), PFS (median 9 versus 3 months, HR 0.34, 95% CI 0.21-0.59), and ORR (34 versus 11 percent). Time to treatment failure was also prolonged with immunotherapy-based regimens (9 versus 3 months).
●By contrast, among patients with non-clear cell RCC lacking a sarcomatoid and/or rhabdoid component, immunotherapy-based regimens were not associated with improved OS (median 24 versus 15 months, HR 0.74, 95% CI 0.46-1.21), PFS (median 4 versus 5 months, HR 1.2, 95% CI 0.85-1.71), or ORR (23 versus 18 percent). Time to treatment failure was similar between the treatment arms (4 versus 5 months).
Lenvatinib plus pembrolizumab — Lenvatinib plus pembrolizumab is an alternative to nivolumab plus ipilimumab in patients with treatment-naïve metastatic sarcomatoid non-clear cell RCC. However, an OS advantage has not been established in this population.
Lenvatinib plus pembrolizumab was evaluated in a single-arm phase II trial (KEYNOTE-B61) of 158 patients with treatment-naïve metastatic non-clear cell RCC [25]. At a median follow-up of 15 months, in the subset of 19 patients with sarcomatoid features, the ORR was 47 percent.
Further details on the efficacy of lenvatinib plus pembrolizumab in patients with advanced clear cell RCC are discussed separately. (See "Systemic therapy of advanced clear cell renal carcinoma", section on 'Lenvatinib plus pembrolizumab'.)
Less preferred regimens
Atezolizumab plus bevacizumab — The combination of atezolizumab plus bevacizumab is also active in those with non-clear cell RCC with a sarcomatoid component [26]. However, this combination does not have regulatory approval as initial therapy for advanced RCC, and its use remains investigational.
Further data on the efficacy of atezolizumab plus bevacizumab in patients with advanced clear cell RCC are discussed separately. (See "Systemic therapy of advanced clear cell renal carcinoma", section on 'Atezolizumab plus bevacizumab'.)
Nivolumab plus ipilimumab and cabozantinib — The combination of nivolumab plus ipilimumab and cabozantinib is active in those with non-clear cell RCC with a sarcomatoid component [27]. The use of this combination remains investigational.
Further details on this combination in patients with advanced clear cell RCC are discussed separately. (See "Systemic therapy of advanced clear cell renal carcinoma", section on 'Nivolumab plus ipilimumab and cabozantinib'.)
Pembrolizumab — Single-agent pembrolizumab (table 5) has clinical efficacy in metastatic non-clear cell RCC with sarcomatoid features, but its use remains investigational.
The efficacy of single-agent pembrolizumab (table 5) in sarcomatoid RCC was demonstrated in an open-label, nonrandomized phase II trial (KEYNOTE-427) consisting of two cohorts. Cohort A had 110 patients with treatment-naïve clear cell RCC, including 11 patients (10 percent) with sarcomatoid features, [22] and cohort B had 165 patients with non-clear cell RCC, including 38 (23 percent) with sarcomatoid features [23].
At median follow-up of 32 months, in the cohort B subset, objective and complete response rates for pembrolizumab in those with sarcomatoid RCC were 42 and 8 percent, respectively (versus 64 and 0 percent in cohort A). Further results for cohort A are discussed separately. (See 'Pembrolizumab' above.)
Further details from this study on the efficacy of pembrolizumab in other non-clear cell histologies are discussed separately. (See "The treatment of advanced non-clear cell renal carcinoma", section on 'Pembrolizumab'.)
Ineligible for immunotherapy — For patients with RCC with sarcomatoid features arising from either clear cell or non-clear histologies who are not eligible for immunotherapy-based regimens, we offer antiangiogenic therapy with VEGFR inhibitors rather than chemotherapy, although this approach has limited efficacy in those with sarcomatoid features. The choice of VEGFR inhibitors in this population is similar to their use in those with clear cell RCC. (See "Systemic therapy of advanced clear cell renal carcinoma", section on 'Ineligible for immunotherapy (intermediate- and poor-risk)'.)
One observational series derived from the IMDC identified 230 patients with sarcomatoid features [28]. Among the approximately 93 percent of patients treated with VEGFR-directed therapy as initial therapy, the overall response rate was 21 percent; median PFS and OS were 5 and 10 months, respectively. Similar objective response rates for single-agent sunitinib were seen in a randomized trial [29].
The effectiveness of mTOR inhibitors for the treatment of sarcomatoid RCC is also limited [4,5]. Although mTOR inhibitors are approved for the treatment of metastatic RCC, immunotherapy-based regimens should be preferred whenever possible for sarcomatoid RCC. (See "Antiangiogenic and molecularly targeted therapy for advanced or metastatic clear cell renal carcinoma", section on 'Inhibitors of the mTOR pathway'.)
Is there a role for other approaches?
Cytoreductive nephrectomy — We do not offer upfront cytoreductive nephrectomy in patients with sarcomatoid RCC, as data suggest poor outcomes with this approach [30]. Upfront cytoreductive nephrectomy is preferred in patients with good performance status, and low disease burden; patients with sarcomatoid RCC are less likely to meet these criteria. Alternatively, select patients with sarcomatoid RCC and a deep partial or complete response of disease outside the kidney to initial systemic immunotherapy could subsequently be offered cytoreductive nephrectomy and surgical resection of residual sites of metastatic disease. (See "Role of surgery in patients with metastatic renal cell carcinoma", section on 'Cytoreductive nephrectomy'.)
Chemotherapy — There is no established role for cytotoxic chemotherapy alone or in combination with targeted therapy in those with RCC with sarcomatoid features. As an example, some studies demonstrated clinical activity for the combination of doxorubicin and gemcitabine in patients with RCC with sarcomatoid features [31], but data overall has not consistently shown clinical efficacy for this approach [32-36].
Active surveillance — Active surveillance is generally reserved for patients with IMDC favorable-risk disease (table 3) who are asymptomatic or minimally symptomatic and have a low disease burden. Active surveillance is not typically offered to those with sarcomatoid RCC because they are unlikely to fit these criteria. (See "Systemic therapy of advanced clear cell renal carcinoma".)
Subsequent therapy — Our approach to subsequent therapy in patients with metastatic sarcomatoid RCC depends on the choice of initial therapy. Clinical trials are encouraged where available, given the rarity of these tumors. Our approach is as follows:
●Progression on nivolumab plus ipilimumab – For patients who progress on initial treatment with nivolumab plus ipilimumab, we offer an antiangiogenic agent rather than the combination of immunotherapy plus antiangiogenic agent. In a randomized trial (CONTACT-03), the latter approach did not improve PFS or OS and increased toxicity relative to antiangiogenic therapy alone, including in the subgroup of patients with sarcomatoid features arising from either clear cell or non-clear cell RCC [37]. Selection of therapy and further details on this trial are discussed separately. (See "Systemic therapy of advanced clear cell renal carcinoma", section on 'Prior immunotherapy with or without antiangiogenic therapy'.)
●Progression on combined immunotherapy plus VEGFR inhibitor – For those who progress on immunotherapy plus VEGFR inhibition, either in combination or via sequential use of these agents, we prefer nivolumab plus ipilimumab (table 2). Other options include antiangiogenic therapy not previously received, such as single-agent cabozantinib, tivozanib, or lenvatinib plus everolimus. (See "Systemic therapy of advanced clear cell renal carcinoma", section on 'Prior immunotherapy with or without antiangiogenic therapy'.)
●No prior immunotherapy – For those who have not yet received immunotherapy (eg, those previously treated with VEGFR inhibitors alone), we offer immunotherapy-based regimens. Our preferred regimen is nivolumab plus ipilimumab (table 2). (See 'Initial therapy (clear cell RCC with sarcomatoid features)' above.)
ASSESSMENT OF TREATMENT RESPONSE — We assess the treatment response of patients with sarcomatoid RCC as follows:
●For most patients, we obtain computed tomography (CT) imaging of the chest and abdomen (with or without pelvic imaging) every two to three months. Brain imaging (eg, magnetic resonance imaging or CT brain) may be obtained as clinically indicated (ie, based on neurologic symptoms). However, since sarcomatoid histology appears to be a risk factor for developing brain metastases, it is also reasonable to offer surveillance brain imaging in asymptomatic patients with metastatic disease [38].
●For patients with clinically aggressive disease at baseline, we image more frequently with CT chest, abdomen, pelvis, and brain imaging every six to eight weeks.
●For patients with prolonged deep partial (ie, greater than 80 percent regression of disease outside the kidney) or complete responses to immune checkpoint inhibitor-based regimens, we reduce the frequency of imaging to every four months to six months, depending upon the duration of response. (See "Principles of cancer immunotherapy".)
PROGNOSIS — Historically, the prognosis of patients with advanced, unresectable, or metastatic sarcomatoid RCC has been poor and treatment has been palliative. Sarcomatoid RCC is associated with limited responsiveness to targeted therapies, such as vascular endothelial growth factor receptor inhibitors or mechanistic target of rapamycin inhibitors [5].
However, both the prognosis and treatment of these patients are evolving in the era of checkpoint inhibitor immunotherapy, and some of these patients may have durable responses. Sarcomatoid RCC generally responds better to immunotherapy-based regimens than nonsarcomatoid RCC, regardless of background histology (ie, clear cell versus non-clear cell). There is currently no evidence that background histology alters management. In patients with sarcomatoid RCC, immunotherapy extends median overall survival to over three years and improves complete response rates, suggesting the potential for cure.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cancer of the kidney and ureters".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Kidney cancer (The Basics)")
●Beyond the Basics topics (see "Patient education: Renal cell carcinoma (kidney cancer) (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Sarcomatoid dedifferentiation – Sarcomatoid dedifferentiation is the most common form of tumor dedifferentiation in renal cell carcinoma (RCC) and can be seen in both clear cell and non-clear cell histologies. (See 'Epidemiology' above and 'Pathologic features' above.)
●Clinical presentation – Patients with sarcomatoid RCC typically present with locally advanced or metastatic disease. The most common presenting symptoms are flank or abdominal pain, hematuria, weight loss, anorexia, fatigue, and night sweats. (See 'Clinical presentation and staging' above.)
●Treatment of localized disease – Patients with localized sarcomatoid RCC are treated with surgical resection. However, the presence of sarcomatoid features often warrants more aggressive surgical treatment, including radical nephrectomy and extended lymphadenectomy. (See "Definitive surgical management of renal cell carcinoma", section on 'Radical nephrectomy' and "Definitive surgical management of renal cell carcinoma", section on 'Retroperitoneal lymph nodes'.)
●Initial therapy for advanced or metastatic disease
•Clear cell RCC with sarcomatoid features – For patients with treatment-naïve advanced or metastatic clear cell RCC with sarcomatoid features, we recommend nivolumab plus ipilimumab (table 2) rather than sunitinib as initial therapy (Grade 1B). Nivolumab plus ipilimumab results in high complete response rates, improves long-term overall survival (OS), and offers most patients the opportunity for treatment-free survival. (See 'Nivolumab plus ipilimumab (preferred)' above.)
-Alternative options to nivolumab plus ipilimumab include combination immunotherapy plus antiangiogenic therapy, although an OS advantage has not been established. Available regimens include nivolumab plus cabozantinib; pembrolizumab plus axitinib; lenvatinib plus pembrolizumab; or avelumab plus axitinib.
•Non-clear cell RCC with sarcomatoid features – For patients with treatment-naïve non-clear cell RCC and sarcomatoid features, we suggest nivolumab plus ipilimumab rather than vascular endothelial growth factor receptor (VEGFR) inhibitors or lenvatinib plus pembrolizumab (Grade 2C) based on observational studies in this population suggesting an OS advantage and extrapolating from data in clear cell RCC with sarcomatoid features. (See 'Nivolumab plus ipilimumab' above.)
Lenvatinib plus pembrolizumab is also an appropriate alternative, although an OS advantage has not been established. (See 'Lenvatinib plus pembrolizumab' above.)
•Ineligible for immunotherapy – For those with sarcomatoid features arising from either clear or non-clear histologies who are not eligible for immunotherapy, we offer antiangiogenic therapy with VEGFR inhibitors rather than chemotherapy, although this approach has limited efficacy in those with sarcomatoid features. The use of VEGFR inhibitors in this population is similar to their use in those with clear cell RCC. (See "Systemic therapy of advanced clear cell renal carcinoma", section on 'Ineligible for immunotherapy (intermediate- and poor-risk)'.)
●Assessment of treatment response – For most patients, we assess treatment response using CT imaging of the chest and abdomen (with or without pelvic imaging) every two to three months. We obtain brain imaging (eg, magnetic resonance imaging or CT brain) as clinically indicated (ie, based on neurologic symptoms). However, it is reasonable also to offer surveillance brain imaging in asymptomatic patients with metastatic disease since sarcomatoid histology appears to be a risk factor for developing brain metastases. (See 'Assessment of treatment response' above.)
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