3 - RCC - SRM & PNx Flashcards
- Viva book done
How would you approach a patient presenting with a renal mass on ultrasound?
I would see the patient in the clinic setting
I would obtain thorough relevant history:
- risk factors (smoking, HTN, obesity, ESRF, family history)
- haematuria / loin pain / loin mass
- constitutional Sx
- paraneoplastic Sx
Past medical history: pre-existing CKD or medical condition that may affect RFT
Physical exam:
- abdominal exam, ballot able kidneys
- any loin scar
- supraclavicular LNs
- non-reducing varicocele (left)
- bilateral LL oedema
Arrange bloods taking for baseline:
- CBC x anaemia / polycythaemia
- Clotting
- dLFT (Stauffer syndrome)
- RFT
- Ca level
Contrast CT Urogram
CT thorax for M staging
DMSA if decreased GFR or multiple/bilateral tumours
How does RCC present?
1) >50% are incidental finding in asymptomatic
2) 30% presents with paraneoplastic syndromes
- Excess erythropoietin (-> polycythemia)
- Excess Renin (-> hypertension, secondary hyperaldosteronism)
- PTHrP (thus hypercalcemia)
- Cortisol (Cushing’s syndrome)
- Gonadotropins (feminisation or masculinisation)
- Stauffer syndrome (benign elevation of liver enzymes)
3) <10% present with classical triad:
- palpable mass
- loin pain
- gross haematuria
Other symptoms include:
- constitutional Sx
- metastatic Sx e.g. cough from lung met, bone pain (30%)
- cervical LN
- LL oedema
- Non-collapsible left varicocele
Risk factors of RCC
1) Smoking
2) Obesity
3) Hypertension
4) Family history (first degree relative)
5) Dialysis with native kidneys in-situ
6) Hereditary syndromes:
- VHL syndrome
- hereditary papillary RCC
- hereditary leomiomyomatosis and papillary RCC
- Birt-Hogg-Dube syndrome
- familial non-syndromic ccRCC
Define “paraneoplastic syndrome”
What are the Paraneoplastic syndromes of RCC?
Definition: A collection of signs and symptoms that results from malignancy but is not due to the local presence of cancer cells
Paraneoplastic syndromes are found in 30% of patients with RCC. Ectopic production of:
- 1,25 dihydroxycholecalciferol, PTHrP → hyperCa
- Renin → hypertension
- Erthropoietin → polycythaemia
- Interleukin 6 and cytokines → Stauffer’s syndrome
- Non-metastatic hepatic dysfunction
- Thrombocytopenia, neutropenia, fever, weight loss and discrete regions of hepatic necrosis are seen - Cytokines → constitutional Sx
- Insulin → hypoglycaemia
- ACTH → Cushing’s
- Gonadotrophin → amenorrhoea, gynaecomastia
- Amyloidosis
- Neuropathy
How to assess renal mass on imaging?
Need to assess:
1) Solid or Cystic
- Solid mass: more likely RCC
- Cystic: simple or complex, Bosniak class by “SICES” (Septum, irregular border, calcification, enhancement, solid component)
2) Size
Mayo 2003 (Frank):
- SRM < 1cm, 50% is malignant
- SRM 1-4cm, 80% is malignant with ~20% aggressive histology
3) Enhancement
- avid enhancement: Oncocytoma, ccRCC
- moderate enhancement: AML, cRCC
- poor enhancement: pRCC
4) Enhancement pattern
- heterogenous pattern: ccRCC
- homogenous pattern: cRCC, oncocytoma, AML
- predominantly enhancing or peripherally enhancing: pRCC
5) Fat Content: AML if +ve
Pathology origin of RCC
RCC is an adenocarcinoma of the renal cortex, arising from the proximal convoluted tubule
CT characteristics of RCC
- Solid component
- Contrast enhancing (by >15 HU defined by EAU)
- 10% contains calcification or fat
“Please interpret this CT” ➔ showing a renal mass
This is a contrast CT scan transverse cut of ______
It showing one ____cm contrast enhancing renal mass, highly suspicious of malignancy:
- size
- location
- clinical T stage
- RENAL (radius, exophytic, nearness to collecting system, anterior, polar line)
- any venous involvement / tumour thrombus
I would also like to assess the hilar anatomy with number and anatomy of renal artery and veins
Review contralateral kidney status
Look for any enlarged LNs or distant metastasis
TNM Staging of RCC
T1 (≤ 7cm)
- T1a: ≤ 4cm
- T1b: >4 to ≤ 7cm
T2 (>7cm)
- T2a: >7 to ≤10cm
- T2b: >10cm but confined to kidney
T3 (extends out but not beyond Gerota)
- T3a:
i) renal veins or segmental branches
ii) pelvicalyceal system
iii) peri-renal or renal sinus fat
- T3b: extends into vena cava below diaphragm
- T3c:
i) extends into vena cava above diaphragm
ii) invades wall of vena cava
T4: Beyond Gerota fascia (including ipsilateral adrenal)
- N1: regional LN
- M2: distant met
Histological subtypes of RCC
- Clear cell (80%)
- highly vascular
- 10% multifocal
- involves loss of VHL, PBRM1 - Papillary (10-15%)
- pseudo-capsule and frequent necrosis
- type 1: better survival
- type 2: more aggressive - Chromophobe (5%)
- arises from cortical portion of collecting duct
- better survival - Collecting duct aka Bellini (rare)
- Medullary cell (rare)
Sarcomatoid → poorly differentiated variant of any subtype
Histological grading of RCC
Most commonly used either ISUP or Fuhrman system:
ISUP RCC Grading
- Grade 1: nucleoli that are inconspicuous and basophilic at 400x magnification
- Grade 2: nucleoli that are clearly visible at 400x magnification and eosinophilic
- Grade 3: have clearly visible nucleoli at 100x magnification
- Grade 4: have extreme pleomorphism or rhabdoid or sarcomatoid morphology
Fuhrman Grading:
Grade 1 = well differentiated
Grade 2 = moderately differentiated
Grade 3 / 4 = poorly differentiated
It is based on nuclear and nucleoli features:
- size
- shape
- nucleolar prominence
- chromatin clumping
Compare Fuhrman grading vs ISUP grading for RCC - what are the pros and cons
Fuhrman grade:
+) Powerful prognostic factor
+) Well known
-) inter-observer reproducibility (Dagher: >20% cannot be graded with Fuhrman)
-) Only for ccRCC, with questionable application in non-ccRCC
ISUP RCC grade:
+) Applicable for ccRCC and papillary RCC
+) Less inter-observer variation
+) Better prognostic information
Indication for renal Bx of renal mass
1) Radiologically indeterminate renal mass (? Abscess / Lymphoma / Metastasis)
2) Before ablative therapy
3) Metastatic disease for targeted therapy without cytoreductive therapy
4) Active surveillance of small renal mass
Complication of renal Bx
Risks include:
1) Bleeding 4.3% (Significant bleeding 0.7%)
2) Pneumothorax 1%
3) AV fistula
4) Seeding (Case reports, <0.01%)
5) Failed biopsies: Inadequate tissue (8% non-diagnostic)
6) Inaccurate biopsies: Wrong histological diagnosis
(Marconi 99.1 / 99.7 / 8 / 90.3 Sen Spec Non-Dx Concor)
What is the significance of renal Bx pathology of oncocytoma?
Poor concordance rate with histology => if renal biopsy showed oncocytoma, only 60% is oncocytoma in surgical specimen
i.e. renal Bx cannot differentiate oncocytoma from:
1) Chromophobe RCC
2) Type 2 or oncocytic variant of papillary RCC
3) Glandular variant of ccRCC with eosinophilic characteristics
How to take a renal Bx?
After reviewing the indication and ruling out any contraindication, I would obtain an informed consent for the procedure.
Patient would be placed in prone position with biopsy done under USG guidance and LA.
18G co-axial needle was used, with at least 2 non fragmented cores, each more than 1 cm in length. (For cT2 or above, at least 4 cores to improve diagnostic accuracy)
Biopsy would be targeted at peripheral region, to avoid necrosis in central region.
How accurate is a renal Bx?
(Macaroni 2016: 99.1 / 99.7 / 8 / 90.3)
Marconi 2016 meta-analysis (EU)
- sensitivity 99.1%
- specificity 99.7%
- non diagnosis 8%
- concordance rate between Bx and nephrectomy 90.3%
Definition of SRM
Enhancing renal mass of less than 4cm in size (Gill NEJM 2010)
Risk of malignancy of renal mass
Predictor of malignancy = size
Mayo (2003) JU:
1) lesion < 1cm, 50% malignancy
2) lesion 1-4cm
- 80% malignancy, with 20% aggressive histology amongst them
- 20% benign
What is the risk of metastasis of SRM?
Chawla meta analysis: 1% met rate
Uzzo (EU 2018) AS series: 2% met rate
Klatte BJUI 2021 ➔ Largest systematic review pooling 18 AS cohorts (~2000 patients with 53month FU) is 2.1% [EAU 2023]
Some evidence for size predicting metastasis (Mayo, MSKCC, Sweden):
i) MSKCC (Thompson, JU 2009):
- <2cm 0% met
- 2-3cm 0.1% met
- 3-4cm 1.8% met
ii) Mayo and Sweden also supports <2cm 0% met
What is the growth rate of SRM
Chawla 0.28
Chawla meta analysis:
- growth rate 0.28cm/year
- size does not predict growth rate, growth rate does not predict malignancy
(Bosniak series 0.36cm/year)
Does size predict metastasis of SRM?
Size mainly predicts malignancy. Some evidence for size predicting metastasis (Mayo, MSKCC, Sweden)
MSKCC (Thompson, JU 2009) involving 2700 patients:
- <2cm 0% met
- 2-3cm 0.1% met
- 3-4cm 1.8% met
Mayo and Sweden also supports <2cm 0% met
What are some indications for AS for SRM?
EAU 2023: “Consider in frail or co-morbid patients after counselling”
AUA: “can be considered if all tumours <2cm”
Indications e.g.:
* Elderly patients with short life expectancy
* Patients with multiple morbidities
* Significant potential for ESRF & RRT, not for PN or radical nephrectomy
* Refuses conventional therapy
What are some prospective studies on AS for SRM?
[EAU 2023][HC]
Brian Lane Study (2010 Cancer)
DISSRM (Delayed Intervention and Surveillance for SRM) (2016 EU by Johns Hopkins)
1) Brian Lane
- >75yo
- Single Centre, 540 patients
- Active treatment in elderly may not have survival benefit due to competing non-cancer cause of death
- at multivariate analysis, management type was not associated with OS after adjusting for age, comorbidities
2) DISSRM
- 497 patients, tumor <4cm
- Intervention vs AS
- 5-year OS was 92% vs 75%
- 5-year CSS was 99% and 100%
- AS was not predictive of OS or CSS in regression modeling with relatively short follow-up
updated in J Urol 2021:
- AS also safe in patients < 60 years old
- CSS in both groups = 100%
- Drawback: Primary intervention group has larger tumor size than AS (2.5 vs 1.5cm)
What are the rationales of doing active surveillance for SRM?
[EAU 2023]
1) Not all SRM are malignant
- Mayo 2003 (<1cm = 50% malignancy, >1cm = 80% malignancy)
2) Slow growth rate of SRM
- Chawla meta analysis growth rate 0.28cm/year
3) Low metastasis risk of SRM
- MSKCC (Thompson, JU 2009) <2cm = 0% metastasis
4) Low mortality / CSM risk from SRM
a) Brian Lane in age >75: Death from tumor progression 4% vs other causes (mostly cardiovascular) 28%; with multivariate analysis showed AS / nephrectomy does not predict OS after adjustment for age / comorbid
b) DISSRM by JHU: “Active surveillance was not predictive of OS or CSS in regression modelling with relatively short follow-up”
- latest 2021 update (JU): CSS both arm is 100%
=> Even AUA guideline 2017 recommendation on AS: “Renal mass < 2cm is safe for active surveillance in all patients”
Do we need renal biopsy before AS for SRM?
[EAU 2023]
Can be considered because:
1) Histological characterisation of grade / pathology SRMs
- useful to select tumours at lower risk of progression for AS
- tailor surveillance imaging schedules.
Finelli EU 2020:
- largest cohort of biopsy-proven, small, sporadic RCCs followed with AS, ccRCC SRMs grew faster than papillary type 1 SRMs (0.25 and 0.02 cm/year on average
2) Also high accuracy and low complication risk of Bx
- (Macaroni 2016: 99.1 / 99.7 / 8 / 90.3)
What are the disadvantages of AS for SRM?
1) No standard protocol for monitoring
2) The trigger point of intervention remained unclear because there are no reliable factors to predict progression except symptoms (Only size predicts chance of malignancy)
3) Delayed intervention will jeopardise chance of NSS
4) Only short to mid-term data; and metastasis is not 0%
- Klatte BJUI 2021 ➔ Largest systematic review pooling 18 AS cohorts (~2000 patients with 53month FU) is 2.1% [EAU 2023]
5) Radiation and contrast risk from serial imaging
6) Psychological burden
- DISSRM interim analysis (2013): Patients undergoing immediate intervention had higher QoL scores at baseline which persists for 1 year. Mental health, which includes domains of depression and anxiety, was not adversely affected while on AS [EAU 2023]
What are the triggering factors for intervention during AS for SRM?
No universally accepted criteria, but overall low threshold for intervention
Based on the AUA 2017 recommendations:
- FU with imaging every 3 to 6 months
- Renal mass < 2cm is safe for AS in all patients
- Triggering factors for intervention:
i) Tumor size > 3cm
ii) growth rate > 0.5cm / year
iii) stage progression
===============
In fact no reliable factor to predict progression except symptoms
Uzzo (2013) proposed trigger factors being:
i) High growth rate
ii) New lesion
iii) Disease progression
iv) Onset of clinical symptoms
