Renal cell carcinoma Flashcards by Ned Jones

RCC response to chemo

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

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Stauffer syndrome

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

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stage of presentation most commonly in RCC

usually localized but a quarter with distant metastatic disease

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RCC mets most commonly to…

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

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RF’s for RCC

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

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Familial syndrome associated with RCC

Von Hippel-Lindau (VHL)

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most common presentation of RCC

Asymptomatic
incidental tumor detection on imaging

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paraneoplastic conditions associated with RCC

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

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CT findings suggestive of malignancy

thickened irregular walls OR septa and enhancement after contrast

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workup of suspected RCC

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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poor prognosticators in metastatic RCC

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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when radical nephrectomy is preferred

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

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stage IV patient management with solitary resectable mass

nephrectomy and metastasectomy

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Role for lymph node dissection in localized RCC

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

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alternative to radical nephrectomy

“nephron-sparing” surgery (Partial nephrectomy)

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

Immunotherapy (CPIs)
VEGF TKI’s
MTOR inhibitors

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Treatment options for advanced/stage IV renal NONclear cell carcinoma

Temsirolimus
VEGF-targeted therapies
IO

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Conditions associated with increased incidence of RCC

NHL
sickle cell

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workup of renal mass concerning for RCC

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

nephrectomy

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Surgical options for RCC

Radical nephrectomy
nephron-sparing surgery (partial nephrectomy)

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indications for radical nephrectomy (generally speaking)

larger tumor
tumor extension into the IVC

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Management of stage IV patient with solitary resectable met

debulking nephrectomy + metastasectomy

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When Is lymph node dissection recommended with radical nephrectomy?

No, only if evidence of lymph node involvement

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Why LDH is ordered for RCC workup + physiology

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

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

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

Trend in incidence of RCC

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

Immunogenicity of RCC

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

tumor vaccines colloquially referred to as

TVs

what does CN stand for

cytoreductive nephrectomy

controversy surrounding cytoreductive nephrectomy in RCC

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.

Stage II RCC definition

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

Stage III RCC definition

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).

Stage IV RCC anatomic definition

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

Preferred regimens for favorable risk metastatic clear cell RCC

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

sunitinib mechanism

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

Role for tissue diagnosis in localized

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

goal of treatment for localized disease

cure

Management of multiple primary renal cell carcinomas

surgery

cabozantinib mechanism

TKI of c-Met and VEGFR2

Management of renal mass questionably cystic vs. solid

Renal US

Tissue of origin of RCC

Renal cortex

Hematuria with RCC suggests what?

Tumor invasion of the collecting system

Presentation of RCC with IVC involvement

peripheral edema, ascites, hepatic dysfunction, pulmonary emboli

Anemia profile in patients with RCC

AICD

Mechanisms of hypercalcemia in RCC

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

multiple primary RCCs associated with what genetic conditions

- VHL - tuberous sclerosis)

Role for immunotherapy in advanced RCC

Approved for first line AND subsequent therapy after targeted therapy

Gist of response to IL-2

- minority of patients respond but responses are durable and majority of complete responders remain free of relapse long term - severe toxicity

Role for Il-2

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

Role for mTOR inhibitors

Second line (not rally anymore…)

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

Radical nephrectomy with adrenalectomy

what is cytoreductive nephrectomy? role for cytoreductive nephrectomy?

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

Role for RT

- conventionally considered a radioresistant tumor, but RT may be useful to treat a single or limited number of mets

Management of brain mets in RCC

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

Primary treatment approach for localized, resectable RCC

Surgery

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

cryoablation RFA

Mangement of small asymptomatic lesions

Active surveillance vs. surgery

Combination IO/TKI regimens

Cabo + nivo Nivolumab + iplimumab Pembro + axitinib

Recurrence rates in general for localized

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

What are the PD-1 checkpoint inhibitors?

nivolumab pembrolizumab

What are the PD-L1 checkpoint inhibitors?

avelumab atezolizumab

What are the VEGF inhibitors used for RCC

Axitinib Sunitinib Pazopanib Bevacizumab Lenvatinib

How is initial therapy in advanced clear cell RCC chosen?

Based on risk class

Risk stratification categories in RCC

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

Risk stratification model used for advanced RCC

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

Stage I management

Partial nephrectomy

Stage II management

Partial or radical nephrectomy

Relapsed metastatic disease management

Clinical trial OR metastasectomy

Surveillance modalities in general for local following definitive treatment

CT abdomen CXR

First line therapy for metastatic clear cell (in general)

VEGF TKI monotherapy OR VEGF TKI + immunotherapy

Tissue of origin of RCC

Renal cortex

What is cytoreductive nephrectomy?

- removal of kidney and primary tumor in the face of metastatic disease - "debulking nephrectomy"

Stage IV management (in general)

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

Role for cytoreductive nephrectomy in stage IV

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

Role for immunotherapy in advanced RCC

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

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

less than 7 cm

Sorafenib targets

VEGFR PDGFR Raf c-KIT FLT3

Model used for risk stratification

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

Common SE of VEGF TKIs

Hypertension

MS and immunotherapy

Generally avoid

Risk factor for medullary renal cancer

sickle cell trait, typically young black men

Second line therapy options

Nivolumab monotherapy Cabozantinib Axitinib lenvatinib + everolimus Sorafenib

Everolimus SE's

pneumonitis + stomatitis

Pazopanib SE to know

Hepatotoxicity

N1 disease = stage?

Stage III

Role for adjuvant therapy in RCC

Stage III disease only

Results for TKIs and mTOR inhibitors in adjuvant settings generally

Data has been underwhelming (immunotherapy does hold promise)

Characteristic proto-oncogene of papillary RCC

c-MET

Clinical significance of developing HTN while receiving therapy with sunitinib

Positive prognosticator

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

Can still do nephrectomy

Stage IV anatomic definition

*invasion beyond Gerota's fascia OR distant mets

Clinical features of leiomyomatosis RCC

- multiple cutaneous leiomyomas - uterine leiomyomata - papillary type 2 RCC

Preferred regimens for favorable risk disease

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

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

Nivo (NOT pembro)

What is the rational for active surveillance in metastatic RCC?

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

Most common histologic variant

Clear cell

Upfront therapy for papillary RCC and why

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

Histologic variants of non clear cell

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

High risk of recurrence warranting adjuvant pembro definition

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)

Regimen that supposedly has better activity for bony disease

Cabo

Stage at which ablative techniques are appropriate

T1a

What is favorable risk in terms of IMDC?

ZERO features

Behavior of Papillary RCC

Tends to be more indolent

HIgh risk (indications for adjuvant IO) for localized

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)