Management of Locally Advanced Kidney Cancer

Daniel Y. C. Heng; Christian Kollmannsberger; Ricardo Rendon; Anil Kapoor

Management of Patients with Locally Advanced Kidney Cancer who are Surgical Candidates

Consensus Statement: There is no indication for neoadjuvant therapy prior to planned surgical resection outside the context of a clinical trial.

– Patients should proceed directly to surgery
– There is currently insufficient evidence to support a general recommendation for neoadjuvant therapy

Consensus Statement: The use of adjuvant therapy following nephrectomy in non-metastatic renal cell carcinoma patients is not currently recommended outside the context of a clinical trial.

– To date, no clinical trial has demonstrated an overall survival (OS) advantage with adjuvant targeted therapy in patients with RCC after curative resection of the primary tumor
– Patients with high-risk tumors who are candidates for complete resection should be encouraged to participate in clinical trials
– Although not currently offered, adjuvant therapy is an exciting field for clinical trials

Completed Trials of Adjuvant Targeted Therapy
Trial	N	Patient characteristics	Treatment arms	Treatment duration	Primary endpoint
S-TRAC¹: Sunitinib trial in adjuvant renal cancer treatment	615	High-risk patients	Sunitinib Placebo	1 year	Disease-free survival (positive results)
ASSURE²: Adjuvant sorafenib or sunitinib for unfavourable RCC	1,943	Non-metastatic RCC; disease stage II–IV; high-risk	Sunitinib Sorafenib Placebo	1 year (9 treatment cycles)	Disease-free survival (negative results)
SORCE³: Sorafenib in patients with resected primary RCC at high/intermediate risk of relapse	1,711	Patients with high- and intermediate-risk resected RCC	Sorafenib Sorafenib/Placebo Placebo	3 years	Disease-free survival (negative results)
EVEREST⁴: Everolimus for renal cancer ensuing surgical therapy	1,545	Pathological stage intermediate or very high-risk patients with full or partial nephrectomy	Everolimus Placebo	9 treatment cycles	Recurrence-free survival (results pending)
PROTECT⁵: Pazopanib as an adjuvant treatment for localized RCC	1,538	Patients with moderately high or high risk of relapse with nephrectomy of localized or locally advanced RCC	Pazopanib Placebo	1 year	Disease-free survival (negative results)
ATLAS⁶: Adjuvant axitinib therapy of renal cell cancer in high risk patients	724	High-risk, non-metastatic RCC with nephrectomy	Axitinib Placebo	3 years	Disease-free survival (negative results)

1: Ravaud A, et al. N Engl J Med. 2016;375:2246–54. [PubMed: 27718781]
2: Haas NB, et al. Lancet. 2016;387:2008–2016. [PMC free article: PMC4878938] [PubMed: 26969090]
3: Eisen TQG, et al. Presented at: ESMO Congress 2019; September 27–October 3, 2019: Barcelona, Spain. Abstract LBA56.
4: Clinicaltrials.gov. NCT01120249. Accessed: June 4, 2020.
5: Motzer RJ, et al. J Clin Oncol. 2017;35:3916–3923. [PMC free article: PMC6018511] [PubMed: 28902533]
6: Gross-Goupil M, et al. Ann Oncol. 2018;29 :2371–2378. [PMC free article: PMC6311952] [PubMed: 30346481]

Pending Trials of Adjuvant Targeted Therapy (Reference: ClinicalTrials.gov)
Trial	Planned accrual	Eligibility	Treatment arms	Primary endpoint	Anticipated completion
IMmotion 010 (NCT03024996)	778	T2 (G4) N0 M0 T3a (G3–4) N0 M0 T3b-4 (G any) N0 M0 Tx (G any) N+ M0 M1 no evidence of disease	Atezolizumab Placebo	Disease-free survival	2022
KEYNOTE-564 NCT03142334)	950	T2 (G4) N0 M0 T3 (Gx) N0 M0 T4 (G any) N0 M0 Tx (G any) N+ M0 M1 no evidence of disease	Pembrolizumab Placebo	Disease-free survival	2022
PROSPER RCC (NCT03055013)	805	T2–4 Nx M0 Tx N1–2 M0	Nivolumab Standard of care	Recurrence-free survival	2023
CheckMate 914 (NCT03138512)	1600	T2a (G3–4) N0 M0 T2b-4 (G any) N0 Tx (G any) N1 M0	Nivolumab+ipilimumab Placebo	Disease-free survival	2022

Management of Patients with Locally Advanced Kidney Cancer who are Medically or Surgically Inoperable

There is currently insufficient evidence to support a general recommendation for neoadjuvant therapy

– Some patients with advanced localized disease deemed medically or surgically inoperable at diagnosis may have a radiological and/or clinical response to systemic therapy
- ▪ Many small studies have demonstrated a potential benefit of systemic neoadjuvant approaches (mostly with VEGF inhibitors)

Patients who do not have the potential to be converted to an operable state should be managed according to the guidance for advanced or metastatic kidney cancer

If there is a question that a patient may be converted to an operable state with systemic therapy, they should be re-evaluated by a multidisciplinary team

For patients (particularly those with hematuria) who are symptomatic, other options such as angioembolization may be considered

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Bookshelf ID: NBK566706

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Practical Approaches to Managing Advanced Kidney Cancer: Version 2020 [Internet].

Management of Locally Advanced Kidney Cancer

Locally Advanced Kidney Cancer Management Algorithm

Management of Patients with Locally Advanced Kidney Cancer who are Surgical Candidates

Management of Patients with Locally Advanced Kidney Cancer who are Medically or Surgically Inoperable

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