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Hematology, oncology > Renal cell carcinoma > Flashcards

Renal cell carcinoma Flashcards

1
Q

RCC response to chemo

A
  • chemo-resistant
  • doesn’t respond well to chemo (<10%), so its use is not recommended
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2
Q

Stauffer syndrome

A

cytokine-mediated paraneoplastic phenomenon in RCC manifested by hepatic dysfunction (elevated LFTs). It resolves after resection of primary tumor.

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3
Q

stage of presentation most commonly in RCC

A

usually localized but a quarter with distant metastatic disease

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4
Q

RCC mets most commonly to…

A

Lung (70-75%), lymph nodes (30-40), bone (20-25%), CNS

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5
Q

RF’s for RCC

A

smoking, obesity, toxic exposures to petroleum products, asbestos, acquired cystic disease of the kidney,
***NHL
sickle cell

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6
Q

Familial syndrome associated with RCC

A

Von Hippel-Lindau (VHL)

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7
Q

most common presentation of RCC

A
  • Asymptomatic
  • incidental tumor detection on imaging
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8
Q

paraneoplastic conditions associated with RCC

A

1) Hypercalcemia from PtHRP
2) polcythemia from increased epo
3) Stauffer syndrome

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9
Q

CT findings suggestive of malignancy

A

thickened irregular walls OR septa and enhancement after contrast

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10
Q

workup of suspected RCC

A

CBC, Chem-7, UA, abdominal + pelvic CT w/ contrast, CXR
Check Chem-7 for elevated ALP
IF elevated → bone scan
IF unclear cystic vs. solid tumor → abdominal US
IF CT contraindicated → MRI
IF concern for renal vein or IVC involvement → MRI abdomen
IF bone pain → Bone scan
IF cough, chest pain → chest CT

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11
Q

poor prognosticators in metastatic RCC

A

1) LDH>1.5x
2) Hgb less than 10
3) Karnofsky performance score <80
4) absence of prior nephrectomy
5) high serum calcium
6) thrombocytosis and leukocytosis

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12
Q

when radical nephrectomy is preferred

A

larger tumors (>7cm) or tumor with IVC extension

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13
Q

stage IV patient management with solitary resectable mass

A

nephrectomy and metastasectomy

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14
Q

Role for lymph node dissection in localized RCC

A

Extended lymph node dissection only done if evidence of lymph node involvement preoperatively

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15
Q

alternative to radical nephrectomy

A

“nephron-sparing” surgery (Partial nephrectomy)

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16
Q

Treatment options for advanced/stage IV renal clear cell carcinoma (in general)

A
  • Immunotherapy (CPIs)
  • VEGF TKI’s
  • MTOR inhibitors
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17
Q

Treatment options for advanced/stage IV renal NONclear cell carcinoma

A
  • Temsirolimus
  • VEGF-targeted therapies
  • IO
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18
Q

Conditions associated with increased incidence of RCC

A

NHL
sickle cell

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19
Q

workup of renal mass concerning for RCC

A

CBC, CMP, UA, abdominal + pelvic CT w/ contrast, CXR
IF elevated ALP → bone scan
IF unclear cystic vs. solid tumor → abdominal US
IF CT contraindicated → MRI
IF concern for renal vein or IVC involvement → MRI abdomen
IF bone pain → Bone scan
IF clinically indicated → brain MRI
IF cough, chest pain → chest CT
IF concern for renal vein or IVC involvement → MRI abdomen

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20
Q

Primary therapy for localized RCC – Stage I, II, II

A

nephrectomy

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21
Q

Surgical options for RCC

A
  • Radical nephrectomy
  • nephron-sparing surgery (partial nephrectomy)
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22
Q

indications for radical nephrectomy (generally speaking)

A
  • larger tumor
  • tumor extension into the IVC
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23
Q

Management of stage IV patient with solitary resectable met

A

debulking nephrectomy + metastasectomy

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24
Q

When Is lymph node dissection recommended with radical nephrectomy?

A

No, only if evidence of lymph node involvement

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25
Q

Why LDH is ordered for RCC workup + physiology

A

Prognosticator. Aerobic glycolysis is the most prominent characteristic of a cancer cell[10]. A large amount of lactate is produced during this process.
- high level of glucose uptake and glycolysis followed by lactic acid fermentation taking place in the cytosol, not the mitochondria, even in the presence of abundant oxygen

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26
Q

RCC histologies and % that are clear cell or non clear cell

A

80% are clear cell RCC (ccRCC) and 20% are non-clear cell RCC (nccRCC)

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27
Q

Trend in incidence of RCC

A

Annual incidence has risen over the past 10  years and now accounts for nearly 4% of new cancer diagnoses in the USA

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28
Q

Immunogenicity of RCC

A

It has significant immunogenic potential. RCC was one of the first tumor models to demonstrate objective tumor responses to CPI.

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29
Q

tumor vaccines colloquially referred to as

A

TVs

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30
Q

what does CN stand for

A

cytoreductive nephrectomy

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31
Q

controversy surrounding cytoreductive nephrectomy in RCC

A

CN is only recommended in patients with a good-to-intermediate prognosis. However, this dogma is challenged by many experts and argues that CN should be considered on an individualized basis and that overarching trials offer RCC patients a disservice by excluding patients who may benefit from CN.

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32
Q

Stage II RCC definition

A

tumor > 7 cm across but still only in the kidney (T2).

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33
Q

Stage III RCC definition

A

Tumor growing into a major vein (like the renal vein or the vena cava) or into tissue around the kidney, but it is not growing into the adrenal gland or beyond Gerota’s fascia (T3). There is no spread to lymph nodes (N0) or distant organs (M0).
OR
(N1) but has not spread to distant lymph nodes or other organs (M0).

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34
Q

Stage IV RCC anatomic definition

A

1) IN SHORT: Tumor growing beyond Gerota’s fascia OR metastatic spread
adrenal gland involvement
**spread to lymph nodes
or distant organs.

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35
Q

Preferred regimens for favorable risk metastatic clear cell RCC

A

Pembro + axitinib (KEYNOTE-426)
Nivolumab + cabozantinib (CHECKMATE-9ER)
Lenvatinib + pembrolizumab

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36
Q

sunitinib mechanism

A

multikinase inhibiotr (RTKs). These include all receptors for platelet-derived growth factor (PDGF-Rs) and vascular endothelial growth factor receptors (VEGFRs),

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37
Q

Role for tissue diagnosis in localized

A

Following partial or radical nephrectomy (limited role for percutaneous biopsy)

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38
Q

goal of treatment for localized disease

A

cure

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39
Q

Management of multiple primary renal cell carcinomas

A

surgery

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40
Q

cabozantinib mechanism

A

TKI of c-Met and VEGFR2

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41
Q

Management of renal mass questionably cystic vs. solid

A

Renal US

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42
Q

Tissue of origin of RCC

A

Renal cortex

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43
Q

Hematuria with RCC suggests what?

A

Tumor invasion of the collecting system

44
Q

Presentation of RCC with IVC involvement

A

peripheral edema, ascites, hepatic dysfunction, pulmonary emboli

45
Q

Anemia profile in patients with RCC

A

AICD

46
Q

Mechanisms of hypercalcemia in RCC

A

1) lytic bone mets
2) overproduction of PTHrP
3) Increased prostaglandin production (promoting bone resorption)

47
Q

multiple primary RCCs associated with what genetic conditions

A
  • VHL
  • tuberous sclerosis)
48
Q

Role for immunotherapy in advanced RCC

A

Approved for first line AND subsequent therapy after targeted therapy

49
Q

Gist of response to IL-2

A
  • minority of patients respond but responses are durable and majority of complete responders remain free of relapse long term
  • severe toxicity
50
Q

Role for Il-2

A

Used to be used more often, but now that there’s better tolerated checkpoint inhibitor immunotherapy, only used for pts who’ve progressed on immunotherapy + have favorable prognostic features

51
Q

Role for mTOR inhibitors

A

Second line (not rally anymore…)

52
Q

Management of patient with advanced disease and direct involvement of ipsilateral adrenal gland without nodal involvment

A

Radical nephrectomy with adrenalectomy

53
Q

what is cytoreductive nephrectomy? role for cytoreductive nephrectomy?

A

“debulking nephrectomy”
- used in select patients prior to initiating systemic therapy with immunotherapy

54
Q

Role for RT

A
  • conventionally considered a radioresistant tumor, but RT may be useful to treat a single or limited number of mets
55
Q

Management of brain mets in RCC

A
  • surgery and/or RT prior to initiation of systemic therapy (hemorrhagic tumors so they can bleed if you give systemic therapy before resecting)
56
Q

Primary treatment approach for localized, resectable RCC

A

Surgery

57
Q

Management of localized disease in older adult patients + patients with comorbid disease who aren’t surgical candidates

A

cryoablation
RFA

58
Q

Mangement of small asymptomatic lesions

A

Active surveillance
vs. surgery

59
Q

Combination IO/TKI regimens

A

Cabo + nivo
Nivolumab + iplimumab
Pembro + axitinib

60
Q

Recurrence rates in general for localized

A

Surgery can be curative but up to 1/3 of patients eventually recur.

61
Q

What are the PD-1 checkpoint inhibitors?

A

nivolumab
pembrolizumab

62
Q

What are the PD-L1 checkpoint inhibitors?

A

avelumab
atezolizumab

63
Q

What are the VEGF inhibitors used for RCC

A

Axitinib
Sunitinib
Pazopanib
Bevacizumab
Lenvatinib

64
Q

How is initial therapy in advanced clear cell RCC chosen?

A

Based on risk class

65
Q

Risk stratification categories in RCC

A

1) favorable
2) intermediate or poor risk (lumped together)

66
Q

Risk stratification model used for advanced RCC

A

International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model

67
Q

Stage I management

A

Partial nephrectomy

68
Q

Stage II management

A

Partial or radical nephrectomy

69
Q

Relapsed metastatic disease management

A

Clinical trial
OR
metastasectomy

70
Q

Surveillance modalities in general for local following definitive treatment

A

CT abdomen
CXR

71
Q

First line therapy for metastatic clear cell (in general)

A

VEGF TKI monotherapy OR VEGF TKI + immunotherapy

72
Q

Tissue of origin of RCC

A

Renal cortex

73
Q

What is cytoreductive nephrectomy?

A
  • removal of kidney and primary tumor in the face of metastatic disease
  • “debulking nephrectomy”
74
Q

Stage IV management (in general)

A

Systemic therapy as per guidelines
*Controversy as to whether debulking nephrectomy should be done upfront

75
Q

Role for cytoreductive nephrectomy in stage IV

A

No clear benefit so not standard of care anymore
- BUT if someone has minimal metastatic burden + good performance status, then it can be considered

76
Q

Role for immunotherapy in advanced RCC

A

Approved in the first line setting alone (ipi/nivo) or in combination with a VEGF TKI depending on risk category

77
Q

Threshold in size for partial nephrectomy (also what differentiates T1 from T2 disease)

A

less than 7 cm

78
Q

Sorafenib targets

A

VEGFR
PDGFR
Raf
c-KIT
FLT3

79
Q

Model used for risk stratification

A

International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model

80
Q

Common SE of VEGF TKIs

A

Hypertension

81
Q

MS and immunotherapy

A

Generally avoid

82
Q

Risk factor for medullary renal cancer

A

sickle cell trait, typically young black men

83
Q

Second line therapy options

A

Nivolumab monotherapy
Cabozantinib
Axitinib
lenvatinib + everolimus
Sorafenib

84
Q

Everolimus SE’s

A

pneumonitis + stomatitis

85
Q

Pazopanib SE to know

A

Hepatotoxicity

86
Q

N1 disease = stage?

A

Stage III

87
Q

Role for adjuvant therapy in RCC

A

Stage III disease only

88
Q

Results for TKIs and mTOR inhibitors in adjuvant settings generally

A

Data has been underwhelming (immunotherapy does hold promise)

89
Q

Characteristic proto-oncogene of papillary RCC

A

c-MET

90
Q

Clinical significance of developing HTN while receiving therapy with sunitinib

A

Positive prognosticator

91
Q

Management of patients with mRCC with resectable primary tumor AND IVC thrombus

A

Can still do nephrectomy

92
Q

Stage IV anatomic definition

A

*invasion beyond Gerota’s fascia
OR distant mets

93
Q

Clinical features of leiomyomatosis RCC

A
  • multiple cutaneous leiomyomas
  • uterine leiomyomata
  • papillary type 2 RCC
94
Q

Preferred regimens for favorable risk disease

A

Pembro + axitinib (KEYNOTE-426)
Nivolumab + cabozantinib (CHECKMATE-9ER)
Lenvatinib + pembrolizumab

95
Q

Immunotherapy approved in second line setting for pts with prior anti-angiogenic therapy

A

Nivo (NOT pembro)

96
Q

What is the rational for active surveillance in metastatic RCC?

A

*a subset of patients have indolent growth of mets. Systemic therapy isn’t curative and is toxic, so risk/benefit may favor surveillance.

97
Q

Most common histologic variant

A

Clear cell

98
Q

Upfront therapy for papillary RCC and why

A

Cabozantinib (MET driven. They derive most benefit from cabo)

99
Q

Histologic variants of non clear cell

A

papillary, chromophobe, collecting duct (including medullary carcinoma), translocation, and unclassified

100
Q

High risk of recurrence warranting adjuvant pembro definition

A

1) T2 with grade 4 or sarcomatoid differentiation
2) T3 or higher
3) regional lymph node metastasis or stage M1 with no evidence of disease (NED)

101
Q

Regimen that supposedly has better activity for bony disease

A

Cabo

102
Q

Stage at which ablative techniques are appropriate

A

T1a

103
Q

What is favorable risk in terms of IMDC?

A

ZERO features

104
Q

Behavior of Papillary RCC

A

Tends to be more indolent

105
Q

HIgh risk (indications for adjuvant IO) for localized

A

1) T2 with nuclear grade 4 or sarcomatoid differentiation
2) T3 or higher
3) node positive
4) stage M1 with no evidence of disease (NED)

Hematology, oncology (218 decks)

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