HYU Onc - Kidney Flashcards
Renal Mass Staging: T1a, T1b
T1a: < or = 4 cm
T1b: < or = 7 cm
Renal Mass Staging: T2a, T2b
T2a: < or = 10 cm
T2b: >10 cm
Renal Mass Staging: T3a
T3a: renal vein, pelvicalyceal, perirenal/renal sinus fat within Gerota
Renal Mass Staging: T3b
IVC below diaphragm
Renal Mass Staging: T3c
VC above diaphragm
Renal Mass Staging: T4
Outside of Gerota or involving adrenal
Stage I
T1N0M0
Stage II
T2N0M0
Stage III
T3N0-1M0
T1-2N1M0
Stage IV
M1
Postoperative Risk Stratification
Low Risk: pT1 and Grade 1-2
Intermediate Risk: pT1 and Grade 3-4, or pT2 and any G
High Risk: pT3 and any G
Very High Risk: pT4 or pN1, sarcomatoid, rhabdoid, macroscopic R1
*Note, positive final margin should increase risk category by one level and increase clinical vigilance
Evaluation of renal mass:
- Imaging?
- Labs?
- CKD?
Get multi-phase cross sectional imaging (enhancing = greater that 20 HU)
Consider MRI if suspicion for IVC thrombus
Get CT chest for advanced tumors
If malignancy suspected –> CBC, UA, CMP, chest imaging
Solid or Bosniak 3/4 mass: Use GFR to assign CKD stage I-V
- (90+, 60+, 30+, 15+, <15 or Dialysis)
When to consult nephrology?
Consider for eGFR <45, expected postop GFR <30, proteinuria, DM with CKD
When to consult Med Onc?
Concerned for potential clinical mets
Incomplete resection
Consider adjuvant treatment for High Risk (T3 and G) or locally advanced, fully resected cancers
When to consult genetics?
Recommend for age 46 or less, multifocal/bilateral renal masses, whenever the personal/family history suggests a familial renal neoplastic syndrome
When to perform Renal Mass Biopsy (RMB)?
Consider if suspicious for hematologic/metastatic/inflammatory/infectious mass
For solid mass, multiple cores»_space; FNA
PPV ~100%, NPV ~60%, Nondiagnostic ~15%
Partial Nephrectomy:
- When do you prioritize this?
- When do you consider it?
- Surgical considerations?
Prioritize PNx: cT1a (when Tx is indicated), cases with solitary kidney, bilateral tumors, familial RCC, multifocal, severe CKD
Consider PNx: young patients, multifocal masses, increased risk for future CKD (HTN, DM, urolithiasis, morbid obesity)
Surgical considerations: minimize warm ischemia time, prioritize negative margins, consider enucleation if familial RCC, multifocal or severe CKD
When is radical nephrectomy preferred over partial nephrectomy?
Radical only preferred over partial if:
1. High tumor complexity and pNx would be difficult even in experienced hands
2. No preexisting CKD or proteinuria
3. Normal contralateral kidney and new baseline GFR likely to be >45
Consider radical when oncologic potential is suggested by tumor size, RMB, and/or imaging characteristics
When is Thermal Ablation appropriate? How to follow up?
Consider for cT1a <3cm AFTER renal mass biopsy
Radio and cryo are options
Counsel slightly worse outcomes (i.e. local recurrence rates)
Can repeat ablation as needed
Obtain pre and post contrast abdominal imaging within 6 months of ablation, then follow IR postop protocol
When to consider active surveillance? Triggers for intervention?
Consider especially for <2cm, repeat imaging in 3-6 months
Consider RMB for mass with solid component
Individualize surveillance based on growth rate and shared decision making (SDM)
Potential triggers for intervention in healthier patients?
- Growth to >3cm
- >5mm/year of growth
Follow-up labs post-op?
Cr, UA, eGFR –> refer to nephrology PRN
Consider other labs as needed and if advanced disease expected (CBC, LDH, LFTs, Alk Phos, Ca++)
Abdominal imaging after nephrectomy and partial nephrectomy?
Chest imaging?
CT w/ and w/o contrast or MRI for 5 years
Consider switching LR and IR patients to alternating cross sectional imaging and abdominal US
SDM for further imaging after 5 years
LR: yearly for 5 years
IR + TA: 6, 12, 24, 36, 48, 60 (q6m for a year)
HR: 6, 12, 18, 24, 30, 36, 48, 60 (q6m for 3 years)
VHR: 3, 6, 9, 12, 18, 24, 30, 36, 48, 60 (every 3 months for a year, then every 6 months to 3 years, then yearly)
Chest imaging: CXR for LR+IR, CT for HR and VHR
SDM after 5 years
What to do when renal artery vasospasm during hilar dissection?
Reduced perfusion
Pale kidney
- Reduce insufflation pressure
- Apply topical papaverine (opium alkaloid antispasmodic vasodilator) to renal hilar vessels
When to consider when using argon gas laparoscopically?
Argon beam will increase abdominal pressure due to addition of argon gas
- Important to vent abdomen via a port to relieve pressure
Interaortocaval nodes only drain the right kidney
They drain the left kidney with advanced disease
Incidence of local recurrence after nephrectomy?
What does this mean for 5 year survival?
Incidence 2.9%
Poor prognosis: 5 year survival 30%
Synchronous mets at the time of recurrence are an independent predictor of poor prognosis
Hand-assisted lap compared to straight lap?
What does this mean for donor nephrectomies?
Hand-assisted lap has higher rates of wound complications (infections and hernias)
In setting of donor nephrectomy, warm ischemia time of donor kidney is reduced because specimen can be quickly removed via hand-port. Other outcomes are similar to straight lap.
Acute bleed following ligation/division of left renal hilum
Think about disruption of a lumbar vein, because this inserted into the renal vein posteriorly
Workflow for urine leak after partial nephrectomy
Start with perc drain placement if drain not already present
If leak persists, make sure drain isn’t directly on leak site, and take off of suction
Place urethral catheter and do RPG + ureteral stent
If unable to place stent, place PCN
Severe, persistent back pain resistant to pain meds after renal surgery
Consider rhabdomyolysis (if pain contralateral to side of surgery, check CK)
Pancreatic injury (if pain is on left following left-sided renal surgery, check amylase and lipase)
Proposed criteria for cytoreductive nephrectomy
Ability to resect >75% of the tumor
No brain mets (need to be treated with radiation or surgery prior to cNx)
Adequate pulmonary and cardiac reserve
ECOG performance status of 0-1
(0=Fully active, able to carry on all pre-disease performance without restriction
1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work)
Predominantly clear-cell histology
Disease has not progressed through systemic therapy (sunitinib)
Vaccinations s/p splenectomy
Indicated due to risk of severe infection with encapsulated bacteria
SHiN - Streptococcus pneumoniae, Haemophilus influenzae type b, Neisseria meningitidis
New lesion with early enhancement and prompt washout at prior tumor site after partial nephrectomy
Get US with doppler to determine pseudoaneurysm vs. recurrence
RCC tumor thrombus levels
0 = renal vein
1 = <2cm into IVC
2 = >2cm into IVC but still below hepatic veins
3 = above hepatic veins but below diaphragm
4 = above diaphragm
3 and 4 may need bypass during sugrery
“Persistent central enhancement”
Tumor recurrence after cryoablation
Ways to optimize (lap) renal cryoablation
Real-time intraop US to monitor progression of cryo lesion
Cryoprobe tip at deepest margin of tumor
Target temperature below -40C
Extend the cryo lesion ~1cm beyond the margin of the tumor
Active double freeze-thaw cycle
Small renal mass(es) are identified in conjunction with widespread LAD outside of typical LN drainage zones
Suspect renal involvement of lymphoma
Perc LN biopsy to determine Tx plan
Renal tumor with high signal on T1 on MRI
Fat in lesion
Think AML
Think a/w tuberous sclerosis
AML = benign tumor of perivascular epithelioid cell origin
MRI sequence most likely to confirm AML
T2 with fat suppression
On CT, suspect AML if negative HU (fat) are mentioned
Angioembolization often effective, particularly in setting of acute bleed
If massive, will need nephrectomy
Drug that can be used to shrink AMLs
Everolimus (Afinitor)
Tumor growth typically resumes when treatment is discontinued
Can watch AMLs when small, can cause problems if >4 cm
Benign tumor in 20yo with elevated peripheral renin
Juxtaglomerular tumor
Tumor secretes renin
patients typically <20yo
Cured with surgery
Rare, extremely aggressive tumor associated with sickle cell trait
Renal medullary carcinoma
- Arises from collecting duct
<100 cases ever
Mean survival <6 months
75% on right side
Central/infiltrative, not amenable to partial
Does not typically respond to chemo/immunotherapies
Treatment for metastatic renal medullary carcinoma
Carboplatin + paclitaxel is first line (not upfront surgical resection)
Gemcitabine + adriamycin is 2nd line
Collecting duct RCC
More aggressive –> younger age of presentation
Resistant to standard chemos for RCC, but sometimes responsive to gemcitabine and cisplatin chemos (behave more like UCC)
Renal pseudotumor
Column of Bertin
Focal cortical hyperplasia
Best established with DMSA scan
How to follow patients with oncocytoma or indeterminate histology on renal mass biopsy
Follow with same imaging protocols used for untreated low risk renal cancers due to risk of substantial growth and risk of inaccurate biopsy results
How to distinguish between oncocytoma and RCC?
Technetium-sestamibi nuclear scanning
- oncocytoma will have high radiotracer uptake
- RCC will have low radiotracer uptake
Preferred regimens for relapse or stage IV metastatic CCRCC (favorable and poor/intermediate risk)
Pembrolizumab + axitinib - Keynote-426
Nivolumab + cabozantinib - CheckMate-9ER
Pembrolizumab + lenvatinib - CLEAR
Cabozantinib monotherapy (CABOSUN) is a preferred option for poor/intermediate risk
Metastatic RCC sites with worst to best prognosis
Brain, liver, bone, LNs, lung, adrenal
What labs do you need to monitor Sunitinib with/for?
Associated with hypothyroidism - get thyroid labs
Renovascular fistulae treatment
- If asymptomatic due to biopsy?
- If asymptomatic due to RCC?
- What symptoms do they cause when symptomatic?
- Cirsoid AV fistula?
- If asymptomatic due to biopsy? 70% will close spontaneously, observe
- If asymptomatic due to RCC? Nephrectomy
- What symptoms do they cause when symptomatic? HTN, hematuria, high output heart failure. Treat with embo, ligation, partial or complete nephrectomy
- Cirsoid AV fistula? Cirsoid means to resemble a varix. These are too complex for angioembolization. Treatment of choice is nephrectomy.
Von Hippel Lindau
- Inheritance pattern?
- Manifestations?
- Gene associated?
- Gene location?
- Leading cause of death in VHL?
- Inheritance pattern? AD
- Manifestations? Hemangioblastomas of retina, cerebellum, medulla (~70%, get brain/spine MRI when diagnosed), cavernous hemangiomas in skin, mucosa and organs, pancreatic masses. About half will develop multiple bilateral RCCs and other tumors associated with deletion of the tumor suppressor gene VHL on 3p
- Gene associated? (VHL (tumor suppressor gene))
- Gene location? Short arm of 3p25
- Leading cause of death in VHL? Kidney cancer
Ipsilateral cysts should be removed at time of partial nephrectomy (when a solid mass is >3 cm) because they can harbor carcinoma
Medication that is FDA approved for treatment of VHL-associated RCC? Mechanism?
Belzutifan (HIF-2a inhibitor)
Common side effects include anemia (from reduced epo), and fatugue
When VHL (a TSG) is deleted, causes constitutive expression of HIF (a transcription factor), which activated angiogenic growth factors (like VEGF, EPO)
Hereditary syndrome with type 1 papillary RCC?
- Gene?
- Location of gene?
Hereditary papillary renal cell carcinoma
RAre
cMet codes for RTK protein –> papillary RCCs only, no extra-renal findings
Hereditary syndrome with type 2 papillary RCC?
Gene?
Location of gene?
Hereditary leiomyomatosis RCC (HLRCC)
FH gene codes for fumarate hydratase (TSG) –> painful leiomyomas (cutaneous, uterine) + papillary RCC –> bad disease, patients may die young –> start annual screening with contrasted MRI at age 8
Surveillance of tumors not recommended, take them out
1q42
Birt-Hogg-Dube
- Gene?
- Gene location?
- Tumor type?
- Manifestations?
Gene - BHD1
On 17p11
Mutated gene codes for folliculin –> painless fibrofolliculomas (benign)
Bilateral RCCs (chromophobe RCC or oncocytomas)
Lung cysts, risk of pneumothorax
Tuberous Sclerosis
- Inheritance pattern?
- Manifestations?
- AD
Facial lesions (adenoma sebaceum)
Hypopigmented “ash leaf spots” on skin
Cortical and retinal hamartomas
Seizures/epilepsy
Mental retardation
Renal cysts
Renal AMLs
Cardiac rhabdomyomas
Increased incidence of astrocytomas
Incomplete penetrance, variable presentation
Lynch syndrome
- Where are mutations?
- What organs most likely to get cancer?
= Hereditary Non-polyposis Colorectal Cancer
- Genes MLH1, MSH2/6, PMS2
- Colorectal, endometrial, digestive, ovarian, upper tract cancers
Cowden Syndrome
PTEN hamartoma syndrome
PTEN = phosphatase and tensin homolog mutations
–> hamartomas
Endometrial and kidney cancers
Li-Fraumeni Syndrome
Tumor suppressor p53 mutation
Breast cancer, osteosarcoma, soft tissue sarcoma, leukemia, lymphoma
Neurofibromatosis
Caused by oncogene mutation in MF1 (csome 17) or NF2 (csome 22)
Classically manifests with cafe au lait spots
MEN 2A
Gain of function in RET proto-oncogene
Medullary thyroid cancer, parathyroid hyperplasia, pheochromocytoma
MEN 2B
Gain of function in RET proto-oncogene
Medullary thyroid cancer, pheochromocytoma, marfanoid body habitus, mucosal neuroma
RCC Screening?
Renal US for ESRD patients after 3 years of dialysis
HLRCC patients at age 8
VHL patients at age 16
Favorable molecular markers for survival in RCC
Absent vimentin, absent p53, High CAIX
Bosniak 1 Classification
Simple cyst, imperceptible wall, no work-up indicated
0% chance of malignancy
Bosniak 2
Minimally complex
A few thin, <1 mm septations or thin calcifications
Non-enhancing high-attenuation (due to proteinaceous or hemorrhagic contents)
Risk of malignancy ~0%
Bosniak 2F
Minimally complex
Increased number of septa
Minimally thickened with nodular or thick calcifications
May be perceived but not measurable enhancement of a hairline smooth thin septa
Hyperdense cyst >3cm in diameter, mostly intrarenal
No enhancement
Requiring follow-up - US or CT around 6 months
Cancer risk 5-10%
Bosniak 3
Indeterminate, thick, nodular, multiple septa or wall with measurable enhancement, hyperdense on CT
Tx: partial nephrectomy or ablation in poor surgical candidates
~50% risk of cancer
Bosniak 4
Clearly malignant
Solid mass with large cystic or necrotic component
Treatment: partial or radical nephrectomy
~100% risk of cancer
Lit: localized RCC in VHL
Belzutifan for localized RCC in VHL
HIF-2a inhibition can shrink small RCCs in VHL
Lit: Radical Nx with or without LND
EORTC
Completely LND NOT needed during radical nephrectomy for N0M0 RCC
- OS, PFS, time to progression and complications rates didn’t differ
Lit: EORTC partial vs radical nephrectomy and renal function
Partial nephrectomy is better than radical nephrectomy for preserving renal function… duh
Similar for OS, median follow-up 9.3 years
Lit: Cytoreductive nephrectomy and interferon
SWOG 8949 2001
cytoreductive nephrectomy and interferon improved median OS by 3 months (11 vs. 8) over interferon alone
Lit: EORTC cytoreductive nephrectomy trial 2001
Cytoreductive nephrectomy + interferon improves median OS by 10 months (17 vs. 7) over interferon alone
A combined analysis for SWOG and WORTC studies similarly revealed a survival benefit with cNx (13.6 vs. 7.8 months)
Lit: CARMENA 2018 (cNx)
cNx + sunitinib has WORSE median OS than sunitinib alone (!)
Lit: SURTIME 2018 (cNx)
Sunitinib + delayed cNx (when indicated) has better OS than upfront cNx
Lit: (not) ASSURE(d) 2016
Adjuvant systemic therapy after rNx
Adjuvant targeted therapy (sunitinib or sorafenib) does not improve disease free survival (DFS) over placebo
Stopped early due to side effects with no evidence of improved DFS with either therapy
Non-metastatic patients
Lit: S-TRAC 2016
Adjuvant systemic therapy after rNx
Adjuvant sunitinib improves median DFS by one year over placebo (no OS benefit)
RCT
Locoregional high risk RCC patients
Lit: KEYNOTE-564 2021
Adjuvant systemic therapy after rNx
Adjuvant pembro improves DFS s/p rNx for high-risk RCC
RCT
OS data immature, but seems to favor pembro group at 24 months
Lit: Global ARCC - Temsirolimus, Interferon-a or both?
2007
Advanced RCC
Temsirolimus identified as best choice for poor-prognosis RCC
RCT
Temsirolimus - mTOR inhibitor
IFN - activates inflammatory and immune responses
Lit: Sunitinib vs. IFN-a for mRCC?
2007
Advanced RCC
Sunitinib > IFN-a for mRCC
PFS and objective response rate better
RCT
Sunitinib - TKI –> VEGF and PDGFR
IFN - activates inflammatory and immune responses
Lit: TARGET 2007
Advanced RCC
Sorafenib > placebo for mRCC s/p 1 prior systemic therapy
RCT
Sorafenib - TKI –> VEGF, PDGFR and RAF kinase
- Significant SE profile includes rare cardiac ischemia
Lit: RECORD-1 2008
Advanced RCC
mccRCC patients who fail sunitinib should get Everolimus
RCT
everolimus –> mTOR inhibitor
PFS was improved in the everolimus group compared to placebo
Lit: COMPARZ 2013
Advanced RCC
Pazopanib is non-inferior to sunitinib for m-ccRCC and has superior safety profile
Pazopanib –> TKI - VEGF, PDGFR, fibroblast growth factor receptor (FGFR), and c-kit
RCT
Median PFS and OS were similar and non-inferior to sunitinib
Lit: METEOR 2015
Advanced RCC
Cabozantinib has better PFS than everolimus for RCC with progression through a VEGFR-targeted treatment
Median PFS and rate or progression or death favored cabozantinib
Lit: CheckMate 025 2015
Advanced RCC
Nivolumab has better OS than everolimus for advanced RCC s/p 1-2 anti-angiogenic Txs (sunitinib)
RCT
Lit: CABOSUN 2017
Advanced RCC
Cabozantinib extends PFS vs. sunitinib in poor/intermediate risk met ccRCC
RCT
Previously untreated patients
Lit: CheckMate 214 2018
Advanced RCC
Nivolumab + ipilimumab has better 18 month OS than sunitinib for poor and intermediate risk patients with untreated advanced RCC (with clear cell component)
RCT
Previously untreated
Ipilimumab = monoclonal Ab to CTLA-4 –> inhibits T-cell suppression
Lit: IMmotion151 2019
Advanced RCC
Atezolizumab + bevacizumab > sunitinib for PD-L1+ mRCC patients
RCT
Patients with mRCC (cc or sarcomatoid)
Atezolizumab = igG4l mAb to PD-L1
Bevacizumab = mAb that inhibits VEGF-A to block angiogenesis
Lit: KEYNOTE 426 2019
Advanced RCC
Pembro + axitinib has increased 1-yr OS over sunitinib REGARDLESS of PD-L1 status
Pembrolizumab = IgG4k mAb to PD-1
Axitinib = TKI –> VEGFR, c-kit, PDGFR
Lit: TIVO-3 2020
Advanced RCC
Tivozanib has better PFS than sorafenib in mRCC s/p multiple prior systemic Tx
RCT
Tivozanib = potent and selective TKI –> VEGF
Sorafenib = TKI –> VEGF, RAF kinase, PDGFR
Lit: CheckMate 9ER 2021
Advanced RCC
Cabozantinib + nivolumab has better OS than sunitinib for previously untreated advanced or mRCC
RCT
Cabozantinib = TKI –> VEGF, MET, TAm
Nivolumab = IgG4 mAb to PD-1 –> inhibits T cell suppression
Cabo/nivo patients have increase QoL
Lit: CLEAR 2021
Advanced RCC
(Lenvatinib + pembrolizumab) > (lenvatinib + temsirolimus) > sunitinib for PFS in previously untreated, advanced RCC
Pembrolizumab = IgG4k mAb to PD-1
Lenvatinib = TKI–> VEGF, FGFR, PDGFR
Sunitinib mechanism
TKI –> VEGF + PDGFR
Decreases tumor angiogenesis and growth
Sunitinib side effects
Myelosuppression, nephrotoxicity, hepatotoxicity, diarrhea, fatigue, nausea, stomatitis, vomiting, HTN, HTN, Hand-Foot Sx, rash
Sorafenib mechanism
TKI –> VEGF + PDGFR + RAF kinase
Decreases tumor angiogenesis and growth
Sorafenib side effects
Cardiac ischemia or infarction (3%), lymphopenia, hepatotoxicity, diarrhea, fatigue, nausea, anorexia, vomiting, HTN, rash
Tivozanib mechanism
TKI –> VEGF
Decreases tumor angiogenesis and growth
Tivozanib side effects
HTN, fatigue, diarrhea, rash, hoarse voice
Cabozantinib mechanism
TKI –> VEGF + MET + TAM
Decreases tumor angiogenesis and growth
Cabozantinib side effects
GI perforation and fistula
HTN
Fatigue
Diarrhea
Rash
Seizures
Jaw osteonecrosis
Anorexia
HA
Dizziness
Nivolumab mechanism
IgG4 mAb to PD-1
Decreases T-cell suppression
Increases T-cells killing cancer cells
Nivolumab side effects
Immune-mediated inflammation, hypothyroidism or hyperthyroidism, pancreatitis with Type I DM, colitis, rash, peripheral edema, neuropathy
Ipilimumab mechanism
IgG1-mAb to CTLA-4
Decreases T-cell suppression
Increases T-cells killing cancer cells
Ipilimumab side effects
Colitis
Diarrhea
Fever
Stomach pain
Bloating
Difficulty breathing
Atezolizumab mechanism
IgG4-mAb to PD-L1
Decreases T-cell suppression
Increases T-cells killing cancer cells
Atezolizumab side effects
Fatigue
Anorexia
Nausea
UTI
Bevacizumab mechanism
IgG1-mAb to VEGF
Decreased tumor angiogenesis
Increased apoptosis
Bevacizumab side effects
HTN
Rash
Nose bleeds
Infection
Lenvatinib mechanism
TKI –> VEGF + FGFR + PDGFR
Decreased tumor angiogenesis
Increased apoptosis
Lenvatinib side effects
HTN
Diarrhea
Fatigue
Anorexia
Hypotension
Thrombocytopenia
Pembrolizumab mechanism
IgG4-mAb to PD-1
Decreased T-cell suppression
Increased T-cells killing cancer cells
(Same mechanism as nivolumab?)
Pembrolizumab side effects
Immune-mediated inflammation
Hypo- or hyperthyroidism
Pancreatitis with Type 1 DM
Colitis
Rash
Fatigue
Diarrhea
Nausea
Axitinib mechanism
TKI –> VEGF, PDGFR, c-kit
Decreases tumor angiogenesis and growth
Axitinib side effects
Diarrhea
HTN
Fatigue
Anorexia
Nausea
Dysphonia
Hand-foot sxs
Weight loss
Vomiting
Constipation
Pazopanib mechanism
TKI –> VEGF, PDGFR, FGFR, c-kit
Decreased tumor angiogenesis and growth
Pazopanib side effects
Nausea
Vomiting
Diarrhea
HTN
Anorexia
Rash
Hair Loss
Fatigue
Temsirolimus mechanism
mTOR inhibitor
Decreased protein synthesis
Decreased tumor survival and growth
Temsirolimus side effects
Fatigue
Rash
Mucositis
Myelosuppression
Hyperglycemia
Everolimus mechanism
mTOR inhibitor
Decreased protein synthesis
Decreased tumor survival and growth
Everolimus side effects
Fatigue
Rash
Diarrhea
Stomatitis
Infections
Myelosuppression
Hyperglycemia
