Adjuvant therapy for renal cell carcinoma: 2023 Canadian Kidney Cancer Forum consensus statement

Question 1

After a patient has had surgery for Renal Cell Carcinoma (RCC), what factors are most notably used to determine their risk of cancer recurrence?

A. Age and weight of the patient
B. Lifestyle habits like smoking and drinking
C. Tumor stage, tumor grade, histological subtype, and other clinicopathological variables
D. Patient’s genetic history

Answer 1

C. Tumor stage, tumor grade, histological subtype, and other clinicopathological variables

Explanation: After a surgery for RCC, the risk of cancer recurrence varies based on several factors. The most notable among them include the tumor stage, tumor grade, histological subtype, and other clinicopathological variables.

Question 2

Why should urologists use nomograms to inform patients about their estimated risk of recurrence after RCC surgery?

A. To inform the patient’s family about the risk of recurrence
B. To decide the surgical approach for future procedures
C. To guide clinical follow-up and inform decisions about potential adjuvant therapies
D. To determine the cost of future medical care

Answer 2

C. To guide clinical follow-up and inform decisions about potential adjuvant therapies

Explanation: Nomograms, which calculate the risk of recurrence after surgery, can help guide the intensity and type of imaging performed during clinical follow-up. This information can also inform decisions about the potential roles of adjuvant therapies. However, it should be noted that nomograms may not entirely capture the risk.

Question 3

According to the Keynote 064 definitions, which patients are eligible for adjuvant pembrolizumab in the intermediate-to-high-risk category?

A. pT1 with grade 2 or sarcomatoid features
B. pT2 with grade 4 or sarcomatoid features, or pT3
C. pT4 or pTanyN1
D. Resected synchronous or metachronous metastases within 12 months of the initial nephrectomy with no evidence of residual disease

Answer 3

B. pT2 with grade 4 or sarcomatoid features, or pT3

Explanation: According to Keynote 064 definitions, patients in the intermediate-to-high-risk category eligible for adjuvant pembrolizumab are those with pT2 with grade 4 or sarcomatoid features, or pT3.

Question 4

Who is considered a high-risk patient eligible for adjuvant pembrolizumab according to the Keynote 064 definitions?

A. pT2 with grade 4 or sarcomatoid features, or pT3
B. pT4 or pTanyN1
C. Resected synchronous or metachronous metastases within 12 months of the initial nephrectomy with no evidence of residual disease
D. pT1 with grade 2 or sarcomatoid features

Answer 4

B. pT4 or pTanyN1

Explanation: Patients in the high-risk category eligible for adjuvant pembrolizumab according to Keynote 064 definitions are those with pT4 or pTanyN1.

Question 5

Which patients with M1 No Evidence of Disease (NED) are eligible for adjuvant pembrolizumab, according to the Keynote 064 definitions?

A. Patients with unresected synchronous metastases within 12 months of the initial nephrectomy with no evidence of residual disease
B. Patients with resected synchronous or metachronous metastases within 12 months of the initial nephrectomy with evidence of residual disease
C. Patients with resected synchronous or metachronous metastases within 12 months of the initial nephrectomy with no evidence of residual disease
D. Patients with resected synchronous or metachronous metastases beyond 12 months of the initial nephrectomy with no evidence of residual disease

Answer 5

C. Patients with resected synchronous or metachronous metastases within 12 months of the initial nephrectomy with no evidence of residual disease

Explanation: According to the Keynote 064 definitions, patients with M1 NED who are eligible for adjuvant pembrolizumab are those who have had resected synchronous or metachronous metastases within 12 months of the initial nephrectomy and have no evidence of residual disease.

Question 6

According to the consensus reached at the CKCF meeting, who should counsel patients about their risk of RCC recurrence post-surgery?

A. General Practitioners
B. Oncologists
C. Urologists
D. Surgeons

Answer 6

C. Urologists

Explanation: The consensus statement indicates that patients who have had surgery for RCC should be counseled by urologists about their risk of recurrence using validated prediction tools.

Question 7

What should be the disease status of patients to be considered for adjuvant therapy?

A. Partially resected clear cell RCC
B. Fully resected clear cell RCC
C. Non-resected clear cell RCC
D. Partially resected non-clear cell RCC

Answer 7

B. Fully resected clear cell RCC

Explanation: The consensus statement suggests that patients should have fully resected clear cell RCC disease (localized or M1 NED) to be considered for adjuvant therapy.

Question 8

Who should patients with resected clear cell RCC at elevated risk of recurrence be referred to?

A. A general practitioner
B. A urologist
C. A medical oncologist
D. A surgeon

Answer 8

C. A medical oncologist

Explanation: According to the consensus statement, patients with resected clear cell RCC at elevated risk of recurrence should be informed about the potential role of adjuvant therapy and be offered a referral to medical oncology.

Question 9

What diagnostic procedures should be performed before starting adjuvant therapy?

A. Cross-sectional imaging of the chest/abdomen/pelvis
B. Biopsy of the surgical site
C. Full body scan
D. Only blood tests

Answer 9

A. Cross-sectional imaging of the chest/abdomen/pelvis

Explanation: The consensus statement specifies that patients should have staging including cross-sectional imaging of the chest/abdomen/pelvis prior to starting adjuvant therapy.

Question 10

When should adjuvant therapy ideally be initiated post-surgery?

A. Within 4 weeks
B. Within 8-12 weeks
C. Within 12-16 weeks
D. After 16 weeks

Answer 10

C. Within 12-16 weeks

Explanation: If adjuvant therapy is provided, according to the consensus, it should be initiated within 12–16 weeks of surgery.

Question 11

What is currently the only treatment that should be considered if adjuvant therapy is provided?
A. Cisplatin
B. Pembrolizumab
C. Paclitaxel
D. Bevacizumab

Answer 11

B. Pembrolizumab

Explanation: According to the consensus statement, if adjuvant therapy is provided, pembrolizumab is currently the only treatment that should be considered.

Question 12

Based on the group definitions of Keynote-564, which patients may be considered for adjuvant systemic therapy?
A. Patients with pT2 clear cell RCC grade 4 or with sarcomatoid features, and pT3 clear-cell RCC disease
B. Patients with pT4 clear cell RCC of any grade and those with N1 clear cell RCC
C. Patients with resected M1 clear-cell RCC and no evidence of disease (NED)
D. All of the above

Answer 12

D. All of the above

Explanation: According to the consensus, patients should be considered for adjuvant therapy based on the group definitions of Keynote-564. This includes all the patient categories mentioned in the options.

Question 13

What should be the duration of treatment if patients receive adjuvant pembrolizumab?
A. Six months
B. One year
C. Two years
D. Until disease recurrence

Answer 13

B. One year

Explanation: If patients receive adjuvant pembrolizumab, according to the consensus, the duration of treatment should be one year.

Question 14

How often should follow-up imaging be performed if patients receive adjuvant therapy?
A. Every 1-2 months
B. Every 3-6 months
C. Every 6-9 months
D. Every 9-12 months

Answer 14

B. Every 3-6 months

Explanation: If patients receive adjuvant therapy, according to the consensus, follow-up imaging should be performed every 3–6 months during therapy.

Question 15

How should follow-up surveillance continue after completion of adjuvant therapy?
A. Per guidelines for metastatic disease
B. Per guidelines for localized disease
C. Only if symptoms of recurrence are noticed
D. No further follow-up is required

Answer 15

B. Per guidelines for localized disease

Explanation: On completion of adjuvant therapy, according to the consensus, follow-up surveillance should continue per guidelines for localized disease.

Question 16

What should be the course of action for patients who experience disease recurrence six months or more after completion of adjuvant therapy?
A. They should be offered second-line treatment for metastatic disease
B. They should be offered standard-of-care first-line treatment for metastatic disease
C. They should be treated similarly to patients who have progressed on first-line immunotherapy for metastatic disease
D. They should be offered palliative care

Answer 16

B. They should be offered standard-of-care first-line treatment for metastatic disease

Explanation: According to the consensus, patients who experience disease recurrence six months or more after completion of adjuvant therapy should be offered standard-of-care first-line treatment for metastatic disease.

Question 17

What should be the course of action for patients who experience disease recurrence during adjuvant therapy or within six months of completion?
A. They should be offered second-line treatment for metastatic disease
B. They should be offered standard-of-care first-line treatment for metastatic disease
C. They should be treated similarly to patients who have progressed on first-line immunotherapy for metastatic disease
D. They should be offered palliative care

Answer 17

C. They should be treated similarly to patients who have progressed on first-line immunotherapy for metastatic disease

Explanation: According to the consensus, patients who experience disease recurrence during adjuvant therapy or within six months of completion should be treated similarly to patients who have progressed on first-line immunotherapy for metastatic disease.

Question 18

Which patients should be considered for adjuvant therapy in the context of Renal Cell Carcinoma (RCC)?
A. Patients with partially resected clear-cell RCC
B. Patients with fully resected clear-cell RCC that was either clinically localized, N+M0, or M1 NED
C. Patients with unresected sites of malignancy
D. Patients with disease that precludes complete local treatment

Answer 18

B. Patients with fully resected clear-cell RCC that was either clinically localized, N+M0, or M1 NED

Explanation: The consensus statement indicates that adjuvant therapy, aimed at reducing the risk of cancer recurrence, should be offered to patients with fully resected clear-cell RCC disease that was either clinically localized, N+M0, or M1 NED. For patients with unresected sites of malignancy, additional local treatments should be considered before systemic treatment. If disease biology or clinical trajectory precludes complete local treatment, systemic therapy in the unresectable/metastatic setting could be considered.

Question 19

At what stage should the possibility of adjuvant therapy be introduced to the patients with clear-cell RCC?
A. After surgery
B. During surgery
C. Prior to surgery
D. At the diagnosis stage

Answer 19

C. Prior to surgery

Explanation: The consensus statement indicates that a discussion about surgical pathology and the risk of recurrence allows the urologist to introduce the role that adjuvant therapy may serve for their patients. This should be mentioned prior to surgery. Postoperatively, patients deemed at an elevated risk of recurrence should be offered a referral to a medical oncologist to further discuss the risks and benefits of adjuvant systemic therapy.

Question 20

How long prior to the start of adjuvant therapy should patients have staging imaging, including cross-sectional imaging of the chest, abdomen, and pelvis?
A. 2-4 weeks
B. 6-12 weeks
C. 3-6 months
D. 1 year

Answer 20

B. 6-12 weeks

Explanation: According to the consensus statement, patients should have staging imaging, including cross-sectional imaging of the chest, abdomen, and pelvis at a reasonable time course before initiating adjuvant therapy. The panel suggests a window of 6–12 weeks prior to start of adjuvant therapy is usually appropriate. Some patients may benefit from additional imaging, especially if there are symptoms suggesting possible metastasis.

Question 21

What is the recommended timeframe for initiating adjuvant therapy after surgery according to the consensus statement?
A. Within 4-8 weeks of surgery
B. Within 8-12 weeks of surgery
C. Within 12-16 weeks of surgery
D. After 16 weeks of surgery

Answer 21

C. Within 12-16 weeks of surgery

Explanation: According to the consensus statement, if adjuvant therapy is provided, it should ideally be initiated within 12–16 weeks of surgery. However, the real-world setting in Canada necessitates commencement within 12 weeks of surgery.

Question 22

As of the consensus statement, which treatment should be considered if adjuvant therapy is provided for RCC?
A. Cisplatin
B. Pembrolizumab
C. Combination ICIs
D. Any PD-1/PD-L1 agents

Answer 22

B. Pembrolizumab

Explanation: The consensus statement indicates that if adjuvant therapy is provided, pembrolizumab is currently the only treatment that should be considered. While in other clinical treatment settings, PD-1/PD-L1 agents may be considered to have similar therapeutic activity, the panel did not feel that single-agent ICIs could be considered interchangeable in the adjuvant RCC setting unless other randomized data provides support to do so. Further, while combination ICIs have been approved in the advanced RCC setting, the panel felt combination ICIs should not be offered as an adjuvant option at this time, outside of clinical trials.

Question 23

What should be the basis for considering patients for adjuvant therapy according to the consensus statement?
A. General health condition of the patients
B. Patient preference
C. Risk group definitions from the Keynote-564 trial
D. Only the stage of the RCC

Answer 23

C. Risk group definitions from the Keynote-564 trial

Explanation: According to the consensus, patients should be considered for adjuvant therapy based on the risk group definitions from the Keynote-564 trial. The panel recommends that these definitions be used for patient selection and counseling when considering adjuvant therapy. It should be noted that while the risk of side effects (harm) from adjuvant therapy may be similar for all groups, the benefit may not be equivalent.

Question 24

According to the consensus statement, which patients with clear-cell RCC may be considered for adjuvant systemic therapy?
A. Patients with pT1 clear-cell RCC
B. Patients with pT2 clear-cell RCC grade 4 or with sarcomatoid features, and pT3 clear-cell RCC
C. Patients with pT2 clear-cell RCC grade 3
D. Patients with pT4 clear-cell RCC

Answer 24

B. Patients with pT2 clear-cell RCC grade 4 or with sarcomatoid features, and pT3 clear-cell RCC

Explanation: According to the consensus statement, patients with pT2 grade 4 clear-cell RCC or with sarcomatoid features, and pT3 clear-cell RCC disease (Keynote-564 intermediate-high-risk group) may be offered adjuvant systemic therapy with pembrolizumab.

Question 25

According to the consensus statement, which high-risk patients with clear-cell RCC may be considered for adjuvant systemic therapy? A. Patients with pT1 clear-cell RCC B. Patients with pT2 clear-cell RCC grade 4 or with sarcomatoid features, and pT3 clear-cell RCC C. Patients with pT4 clear-cell RCC of any grade and those with N1 clear-cell RCC D. All patients with clear-cell RCC

Answer 25

C. Patients with pT4 clear-cell RCC of any grade and those with N1 clear-cell RCC Explanation: The consensus statement indicates that patients with pT4 clear-cell RCC of any grade and those with N1 clear-cell RCC (Keynote-564 high-risk group) may be offered adjuvant systemic therapy with pembrolizumab.

Question 26

According to the consensus statement, which patients with M1 clear cell RCC may be considered for adjuvant systemic therapy? A. Patients with active M1 clear cell RCC B. Patients with resected M1 clear cell RCC and no evidence of disease (NED) C. Patients with untreated M1 clear cell RCC D. All patients with M1 clear cell RCC

Answer 26

B. Patients with resected M1 clear cell RCC and no evidence of disease (NED) Explanation: The consensus statement indicates that patients with resected M1 clear-cell RCC and no evidence of disease (NED) may be offered adjuvant systemic therapy with pembrolizumab. In the Keynote-564 trial, this population was defined as those patients with M1 stage and no evidence of disease after complete resection of oligometastases synchronously or within one year of nephrectomy.

Question 27

According to the consensus statement, what should be the duration of treatment if patients receive adjuvant pembrolizumab? A. Six months B. One year C. Two years D. Until the disease recurs

Answer 27

B. One year Explanation: The consensus statement indicates that if patients receive adjuvant pembrolizumab, the duration of treatment should be one year. This recommendation follows the current evidence available from Keynote-564, where a one-year treatment protocol was used.

Question 28

According to the consensus statement, how often should follow-up imaging be performed if patients receive adjuvant therapy? A. Every 1-2 months B. Every 3-6 months C. Every 6-12 months D. Once a year

Answer 28

B. Every 3-6 months Explanation: The consensus statement indicates that if patients receive adjuvant therapy, follow-up imaging should be performed every 3–6 months during therapy.

Question 29

According to the consensus statement, how should follow-up surveillance proceed after the completion of adjuvant therapy? A. Follow-up surveillance should be discontinued. B. Follow-up surveillance should continue per guidelines for metastatic disease. C. Follow-up surveillance should continue per guidelines for localized disease. D. The frequency of follow-up surveillance should be increased.

Answer 29

C. Follow-up surveillance should continue per guidelines for localized disease. Explanation: According to the consensus statement, after the completion of adjuvant therapy, follow-up surveillance should continue per guidelines for localized disease. The panel suggests that for patients who completed ICI therapy with no significant immune-related adverse events (irAEs), the follow-up could return to the urologist or urologic oncologist for standard surveillance.

Question 30

According to the consensus statement, what should be offered to patients who experience disease recurrence six months or more after completion of adjuvant therapy? A. Second-line treatment for metastatic disease B. Standard-of-care first-line treatment for metastatic disease C. Continuation of the adjuvant therapy D. Palliative care

Answer 30

B. Standard-of-care first-line treatment for metastatic disease Explanation: According to the consensus statement, patients who experience disease recurrence six months or more after completion of adjuvant therapy should be offered standard-of-care first-line treatment for metastatic disease.

Question 31

According to the consensus statement, how should patients who experience disease recurrence during adjuvant therapy or within six months of completion be treated? A. They should be offered palliative care B. They should be treated similarly to patients who have progressed on second-line immunotherapy for metastatic disease C. They should be treated similarly to patients who have progressed on first-line immunotherapy for metastatic disease D. They should continue on the adjuvant therapy

Answer 31

C. They should be treated similarly to patients who have progressed on first-line immunotherapy for metastatic disease Explanation: According to the consensus statement, patients who experience disease recurrence during adjuvant therapy or within six months of completion should be treated similarly to patients who have progressed on first-line immunotherapy for metastatic disease.

Question 32

According to the discussion, who should be referred to medical oncology for consideration of adjuvant therapy? A. All patients with RCC B. Patients with metastatic RCC only C. Clear-cell RCC patients based on the Keynote-564 risk groups D. Non-clear-cell or variant histologies of RCC

Answer 32

C. Clear-cell RCC patients based on the Keynote-564 risk groups Explanation: According to the discussion, referral to medical oncology should be considered for eligible clear-cell RCC patients based on the Keynote-564 risk groups. This is because the treatment is now accessible in Canada, and these patients could potentially benefit from it.

Question 33

According to the discussion, which of the following factors might explain the discrepant outcomes in ICI-based adjuvant trials? A. Differences in the classification of patient populations B. Differences in the mechanism of agents studied C. Differences in the duration of therapy D. All of the above

Answer 33

D. All of the above Explanation: The discussion highlights that there could be many reasons for the inconsistent results reported in ICI-based adjuvant trials. Some potential explanations include differences in the classification of patient populations, the mechanism of the agents studied, and the duration of therapy, among others.

Question 34

According to the discussion, why is overall survival (OS) data particularly important when considering an adjuvant treatment? A. Because adjuvant treatment is less toxic than other treatments B. Because adjuvant treatment exposes many patients, who may never recur, to toxicity C. Because adjuvant treatment is less expensive than other treatments D. Because adjuvant treatment is more widely available than other treatments

Answer 34

B. Because adjuvant treatment exposes many patients, who may never recur, to toxicity Explanation: The discussion emphasizes that overall survival (OS) data is crucial when considering an adjuvant treatment. This is particularly important because adjuvant therapy exposes many patients, who may never experience a recurrence, to potential toxicity. Therefore, if patients who do recur could achieve similar OS and quality of life outcomes with salvage therapy at the time of recurrence, this latter option may be more desirable for many patients.

Question 35

According to the discussion, what percentage of patients experienced grade 3 or higher adverse events (AEs) in the pembrolizumab arm of Keynote-564? A. 18% B. 32% C. 50% D. 68%

Answer 35

B. 32% Explanation: The discussion reveals that in Keynote-564, grade 3 or higher adverse events (AEs) were observed in 32% of patients in the pembrolizumab arm, compared to 18% in the placebo arm. These data highlight the importance of carefully considering the risks of ICI treatment and balancing them against potential benefits in a curative-intent clinical context.

Question 36

Based on the conclusions, which immunotherapy agent has been shown to prolong Disease-Free Survival (DFS) in the adjuvant setting for resected clear-cell RCC? A. Nivolumab B. Ipilimumab C. Pembrolizumab D. Durvalumab

Answer 36

C. Pembrolizumab Explanation: The conclusion of the paper clearly states that pembrolizumab is the only immunotherapy agent so far that has been shown to prolong Disease-Free Survival (DFS) in the adjuvant setting for patients with resected clear-cell Renal Cell Carcinoma (RCC).