Dr JOY NARAYAN CHAKRABORTY

MS, DNB Urology, DNB Surgery, FRCS Edinburgh.

Viva
FRCS England, FRCS Urology, FHEA
Postgraduate Tutor, Surgical & Urological Sciences,
To pCANCER
RENAL ic 6
Edinburgh University, UK

RENAL CANCER 6

CONTACT
[email protected]
54–year-old male presents with a palpable mass in the right loin with intermittent painless haematuria for
one month. He is a chronic smoker and hypertensive on oral medications. BMI 30.

How would you proceed in this case ?

History & Physical Examination
• Haematuria, Loin pain, Swelling (Triad)
• ? Smoking / obesity / Hypertension
• ? Family History
• ? Bone pain
• ? Neurological symptoms
• ? Local symptoms

Physical Examination
• No anaemia, pedal edema
• No SC LNs
• Palpable Large right loin mass
• No varicocele
• No anaemia
• No cachexia What next ?
Laboratory tests and Imaging study

• Serum creatinine, eGFR, CBC

• Blood count (platelet count, Neutrophil count, Lymphocyte count), Hb%, ESR, LFT, Alkaline phosphatase,
LDH
• Serum corrected Calcium, Coagulation study, and Urinalysis
• Performance status (PS)
• C-reactive protein (CRP)
• Albumin
• and various indices deriving from these factors such as the Neutrophil-to-lymphocyte ratio (NLR)
+
’Renal characterisation’ CECT
Can you briefly describe the findings ?
Contrast-enhanced two coronal and one axial film of KUB area in the coticomedullary phase showing
• Large right renal tumour, strongly and heterogeneously enhancing
• Central hypodense area corresponds to areas of necrosis
• The tumour is seen extending to the undersurface of the liver
• Perirenal fat stranding present, however, Xerota’s fascia intact
• Upper pole is grossly uninvolved
• No evidence of venous thrombus
• There is a functioning contralateral kidney
• Adrenals are uninvolved
• No grossly enlarged regional LNs
I need to look at all the films

I would arrange for a Metastatic evaluation

In this case, I will arrange for a CT Chest and Abdomen
Chest CT

Left solitary lung metastasis

No involvement of abdominal solid organs
No gross nodal involvement

What next ?
I will arrange a RRM (Radiology review meeting) to confirm the:
• Extent of the primary tumour and other abdominal or distant metastasis
• Resectability of the mass
RRM confirms the previous findings
15 x 14 cm right renal mass with Preservation of perinephric fat and the mass is apparently surgically
resectable

Can you sum up the clinical, laboratory and imaging results to come up with a clinical diagnosis ?
Large Right renal mass a solitary left pulmonary metastasis
C T3a N0 M1

Which IMDC Risk-group does this patient belong to ?

Which one is more commonly used ?
Which IMDC Risk-group does this patient belong to ?

Karnofsky Performance status 80%

Interval from diagnosis to treatment 3 months
Hb 10.5 mg/dl
Ca 10 mg/dl
Neutrophil count 6 x 106/ml
Platelet count 300,000
LDH: WNL

Hence this case belongs to the ‘IMDC favourable-risk’

What are the factors included in ‘MSKCC’ and ‘IMDC’ Prognostic models for mRCC ?
mRCC Prognostic Models : MSKCC Model

Formulated in the Pre-targeted

therapy era

PIHCaL
mRCC Prognostic Models : IMDC Model ***

Differences from MSKCC Model

• Formulated in the Post-Targeted

therapy era
• Addition of Neutrophil and Platelet
count

2-year survival
PIHCaNP
Favourable 43%
Intermediate 22%
Poor 2%
How would you manage this patient ?

MDT Discussion
As this patient belongs to a Favourable-risk group, I would like to perform a ‘Upfront Cytoreductive
nephrectomy’

Would you like to perform any other imaging before CN ?

Would you like to perform any other imaging before CN ?

• Brain CT : No evidence of metastasis

• Whole body MRI for bone metastasis : No evidence of metastasis

What do you mean by Cytoreductive Nephrectomy ? Why are you selecting this option ?
What is Cytoreductive Nephrectomy (CN) ? Why are you selecting ‘Upfront CN’ for this option ?

‘CN’ is the surgical removal of the primary tumour bearing kidney in patients with mRCC and is aimed at
reducing the tumour burden of the patient.
• CN is palliative for most of the renal cancer patients with high tumour burden + widespread metastasis
• CN is potentially curative in some patients with low tumour burden + single/oligometastatic disease

I prefer to select an ‘upfront CN’ for this patient because

1. IMDC Favourable-risk category patient
2. Comparatively younger patient with good PS
3. Technically resectable as per RRM discussion
4. No Brain, Bone, Liver metastasis (BBM : known bad metastatic locations)

What does the ‘CARMENA’ and ‘SURTIME’ Trial is all about ?

Both CARMENA & SURTIME Trial demonstrated that Upfront systemic therapy is beneficial for at least the
IMDC intermediate and poor-risk groups

CARMENA Trial SURTIME Trial

• a phase III non-inferiority RCT investigating • RCT: sequencing ‘CN followed by sunitinib’ or
immediate CN followed by sunitinib vs. sunitinib ‘sunitinib followed by CN’ did not affect PFS
alone
• Sunitinib alone is not inferior to CN followed by
sunitinib with regard to OS

What are the advantages & disadvantages of CN ?

Advantages & Disadvantages of ‘Upfront Cytoreductive Nephrectomy’

ADVANTAGES DISADVANTAGES
1. Removal of the immunogenic sink (tumour 1. After CN, there may be delay in initiating
continuously producing Growth factors & systemic therapy due to surgical morbidity
Cytokines) postpone metastatic progression & 2. Presurgical systemic therapy and deferred CN
nephrectomy-activated azotemia
may identify patients with inherent resistance
2. Improved OS in favourable-risk patients to systemic therapy without an increase in the
risk of inferior oncological outcomes and
3. Effective response of the Immune Checkpoint
inhibitors (ICI) in post-CN setting if added at a without concern for worse surgical morbidity
later date profile.

What are main determining factors for upfront-CN vs Systemic therapy ?

Main determining factors for upfront-CN vs Systemic therapy

• Resectability of the Primary tumour

• Performance status
• Oligometastatic / widespread metastasis
• Presence / absence of adverse metastatic location
• IMDC Risk-group

How these factors help formulating the treatment options in mRCC ?

 Primary mRCC
MDT Discussion

Primary mRCC not requiring systemic therapy Primary mRCC requiring systemic therapy
Resectable disease Unresectable disease
Good PS Poor PS
No adverse Metastasis Adverse Metastasis

IMDC Favourable Risk IMDC Intermediate Risk IMDC Poor Risk

Upfront Cytoreductive Systemic Therapy

Nephrectomy One Factor Two factor

Discuss Good Response

Delayed Cytoreductive to Systemic
Nephrectomy Therapy
After CN, how would you follow this patient up ?
Follow-up schedule after CN

Surveillance after treatment for RCC allows the urologist to assess:

• Post-operative complications
• Renal function
• Local recurrence
• Recurrence in the contralateral kidney
• Progression of metastases
1. Larcher A, Wallis CJ, Bex A, Blute ML, Ficarra V, Mejean A, Karam JA, Van Poppel H, Pal SK. Individualised
indications for cytoreductive nephrectomy: which criteria define the optimal candidates?. European Urology
Oncology. 2019 Jul 1;2(4):365-78.
2. Ljungberg B, Albiges L, Abu-Ghanem Y, Bedke J, Capitanio U, Dabestani S, Fernández-Pello S, Giles RH,
Hofmann F, Hora M, Klatte T. European Association of Urology guidelines on renal cell carcinoma: the 2022
update. European urology. 2022 Mar 26.
3. Bhindi B, Graham J, Wells JC, Bakouny Z, Donskov F, Fraccon A, Pasini F, Lee JL, Basappa NS, Hansen A,
Kollmannsberger CK. Deferred cytoreductive nephrectomy in patients with newly diagnosed metastatic renal
cell carcinoma. European urology. 2020 Oct 1;78(4):615-23.
4. Kuusk T, Szabados B, Liu WK, Powles T, Bex A. Cytoreductive nephrectomy in the current treatment algorithm.
Therapeutic advances in medical oncology. 2019 Sep;11:1758835919879026.
5. Ghatalia P, Handorf EA, Geynisman DM, Deng M, Zibelman MR, Abbosh P, Anari F, Greenberg RE, Viterbo R,
Chen D, Smaldone MC. The role of cytoreductive nephrectomy in metastatic renal cell carcinoma: a real-world
multi-institutional analysis. The Journal of urology. 2022 Jul;208(1):71-9.
6. Bakouny Z, El Zarif T, Dudani S, Wells JC, Gan CL, Donskov F, Shapiro J, Davis ID, Parnis F, Ravi P, Steinharter JA.
Upfront cytoreductive nephrectomy for metastatic renal cell carcinoma treated with immune checkpoint
inhibitors or targeted therapy: an observational study from the International Metastatic Renal Cell Carcinoma
Database Consortium. European Urology. 2022 Oct 20.