Take Home Messages: Kidney Cancer

Kara N. Babaian, MD

No Disclosures

Kidney Cancer Take Home MessagesPlenary Session

• Kidney Tumor Board

• Survivor Debate: 3.5cm Renal Mass in a 71M

• Tips & Tricks: Robotic Partial Nx

• Crowdsourcing: Renal Hilar Dissection

• Journal of Urology Lecture: Evolving strategies in the management of small renal masses

• Crossfire:

• RN for T1b/T2 Renal Cancer

• Cytoreductive radical therapy still has a role in the era of targeted therapy for mRCC

Kidney Cancer Take Home Messages

• Renal mass biopsy

• Novel imaging for diagnosis

• Active surveillance

• PN for >4cm tumors

▪ 180 Abstracts presented in• 5 Podium Sessions• 6 Moderated Poster Sessions

• Renal function outcomes• Surveillance Imaging: when, how?• Predictors of outcomes / response

to systemic therapy• Cytoreductive Nephrectomy

▪ Most Common Themes

Take Home MessagesBiopsy

• RM biopsy decreases treatment of benign tumors• PD07-09(Wallis et al), MP14-04 (Cheung et al), MP14-05 (Tringali et al)

• MP31-15 (Best Poster): Renal mass biopsy vs biopsy in other organs (Jefferson et al)

Take Home MessagesImaging

• New imaging techniques are under investigation to differentiate between benign and malignant tumors and identify aggressive tumors

• MP14-02: 99mTc-sestamibi SPECT/CT differentiated oncocytoma and hybrid tumors from other histologies with 87% Se and 89% Sp (Meyer et al)

• MP19-02: CT radiomic features discriminated between sarcomatoid and nonsarcomatoid RCC with 93% Se and 94% Sp (Suk-Ouichai et al)

Imaging + Biopsy to prevent surgery for benign renal mass

▪ MP19-01 (Best Poster): Automated CT measurement of Peak early-phase enhancement ratio (PEER) >0.5 can distinguish between oncocytoma and chromophobe RCC (Aldhaamet al) with 95% accuracy

• PEER= ratio of signal intensity differences between early and delayed contrast phases for the peak enhancing portion of the tumor compared to the renal cortex

▪ MP14-06: Prevention of benign tumor resection using biopsy and PEER evaluation (Menon et al)

• N=141 underwent bx

• 35 Biopsy CD117 + oncocytic tumors confirmed to be oncocytoma by PEER value (>0.55) were placed on AS. No surgical Pt had benign histology

Take Home MessagesActive Surveillance

• In Pts with germline alterations, tumors with BAP1/VHL (ccRCC) mutations grow the fastest; FLCN (BHD, chromophobe) and MET (HPRCC, Papillary type 1), the slowest

• PD07-04: Characterized growth rate of 340 genetically defined tumors on AS (Ball et al)

• AMLs can be safely observed

• MP14-01 (Best Poster): Natural History of AML favors surveillance (Nason et al)

• 56% of Pts requiring intervention were symptomatic at presentation

• <4cm NNT to prevent 1 intervention = 82

• ≥4cm NNT to prevent 1 acute event =16

Take Home MessagesActive Surveillance

• Counseling important to address anxiety in Pts who are appropriate candidates for AS

• MP14-10: In 371 Pts on AS (DISSRM), most common indications for intervention were growth rate (50%) and patient preference (48%) (Gupta et al)

Take Home MessagesSurgical Therapy

▪ MP42-13 (Best Poster): RN associated with new-onset and worsened HTN compared to PN, including older Pts and Pts with normal kidney function (Shah et al)

N=3,106HR 1.40

N=6,250HR 1.18

Take Home MessagesSurgical Therapy

▪ PN is feasible in well selected Pts with tumor >4cm

▪ MP37-08 (Best Poster): Outcomes with RAPN for cT3a renal masses (Bindayi et al)

• n=100, median tumor size 7.7cm, median RENAL score 9

• 6% pos margin, 8% major complication

• Primary endpoint: 1. neg margins, 2. WIT < 25min, 3. No complications = 64%

• Optimal outcome: 1. ≥90% eGFR preservation, 2. No CKD upstaging = 41%

• 5yr RFS 77%

▪ Partial Nephrectomy has similar oncologic outcomes to RN in retrospective cohorts

• MP42-17, Patel et al; MP37-07, Na et al; MP42-20, Okhawere et al; PD41-05, Bradshaw et al

Renal Function Outcomes▪ MP-31-05: Evaluated renal functional and parenchymal compensation in 273 RN Pts

with nuclear renal scans (Palacios et al)

• Renal function compensation=percent change in GFR. Renal parenchymal compensation=percent change in parenchymal volume

• RF compensation increased median 126% during first 3 mo then stable to 5 yrs

• RP compensation increased median 10% up to 12 mo

• Functional efficiency per unit of parenchymal volume increased 10% (0.21 to 0.23 GFR units/cm3)

• Younger age, lower global preop GFR, higher GFR removed kidney were independent predictors of percent functional compensation

Renal Function Outcomes• MP31-12: Urine Alb/Cr ratio predicts kidney function outcomes after nephrectomy

(Sun et al)

• MVA demonstrated that moderate (n=658, 34%) and severe (n=157, 8%) albuminuria was significantly associated with eGFR <30 in both radical and partial nephrectomy

Take Home MessagesRenal Function Outcomes

• Functional compensation after RN is due to increase in parenchymal mass and in filtration efficiency

• Moderate and severe albuminuria as measured by Urine Alb/Cr ratio predicts for CKD after RN and PN

Surveillance Imaging• PD07-05: Chest imaging during Active Surveillance for SRM (Kassiri et al)

• Actionable Findings: lung (63%) and thyroid (25%) nodules

• No Pt had metastatic RCC

19%

43% 11%

43%32(12%) of 268 Actionable

DISRRM Registry

Surveillance Imaging

• MP14-14: Modeling competing risks of recurrence and non-RCC death in non-metastatic RCC to determine when surveillance can be discontinued (Merrill et al)

• Age, Stage, histology, ECOG PS

Cumulative Incidence Functions by Stage and Histology for ECOG 0 Patients

(MP14-14, Slide courtesy of Dr. Suzanne B. Merrill, Penn State)

Age 70Age 50

Estimation (in years) When RCC Surveillance May Be Discontinued(MP14-14, Slide courtesy of Dr. Suzanne B. Merrill, Penn State)

Estimates may improve provider decisions of when focus of care can transition to more important health conditions

Age ECOG Histology Stage

pT1aN0-x pT1bN0-x pT2N0-x pT3aN0-x pT3b/c/4N0-x

50 0

Clear Cell 4.4 (10.4) 9.3 (> 13.9) 13.3 (> 13.9) > 13.9 > 13.9

Papillary 3.6 (10.9) 7.2 (> 13.9) 12.4 (> 13.9) > 13.9 > 13.9

Chromophobe -- -- 3.3 (13.4) > 13.9 > 13.9

70 0

Clear Cell -- -- 2.5 (9.4) 13.3 (> 13.9) 13.7 (> 13.9)

Papillary -- -- 1.6 (10.5) 12.5 (> 13.9) 13.2 (> 13.9)

Chromophobe -- -- -- 3.3 (> 13.9) 3.9 (> 13.9)

1/5 recurred outside common imaging templates

PD46-08: Early recurrence patterns in ≥pT3a M0 RCC (Dreyfuss et al)(Slide courtesy of Drs. L Dreyfuss and EJ Abel)

Take Home MessagesSurveillance Imaging

• Routine chest imaging for Pts with SRM on AS unlikely to detect metastatic disease

• Competing risk analysis using age, T Stage, histology and ECOG PS can estimate when surveillance can be discontinued

• Chest, abdomen, AND pelvis imaging will identity the majority of recurrences within 2 years after surgery for high risk RCC

C-reactive Protein as a Predictor of Outcome▪ Localized Disease

▪ MP31-16: Elevated CRP >0.5mg/L associated with development of de novo Stage III/IV CKD after R/PN (Cotta et al)

▪ MP19-10: Pre-treatment CRP >10mg/L was an independent predictor of worse RFSin papillary RCC (Toide et al)

▪ PD41-11: Pre-treatment CRP >0.5mg/dl was an independent predictor of worse OS (Patel et al)

▪ MP14-16: Increased mGPS after surgery from baseline of 0 was an independent predictor of worse OS in ccRCC (Patil et al)

C-reactive Protein as a Predictor of Outcome▪ Metastatic Disease

▪ PD03-06: CRP/albumin ratio ≥0.05 was an independent predictor of worse OS (Konishi et al)

▪ MP25-09: CRP flare-responder (25%) associated with improved response to Nivolumab (-35% tumor shrinkage, 63% ORR) compared to CRP responder (-8%, 8%) and non-CRP responder (+19%, 0%) (Fukuda et al)

Take Home Messages Predictors of Outcome

• Elevated CRP is a predictor of worse survival in Pts undergoing surgery for localized RCC and in Pts undergoing TKI therapy for metastatic RCC

• CRP flare-responders have the best response to Nivolumab in the metastatic setting

• Significance: Identify Pts for adjuvant treatment, clinical trials, and change of systemic therapy

Response to Adjuvant Therapy▪ MP25-17 (Best Poster): Neutrophil and Platelet to Lymphocyte ratio in S-TRAC Pts

(Patel et al)

▪ S-TRAC (Ravaud et al, N Engl J Med 2016;375:2246-54)

▪ Out of 5 published adjuvant RCTs, only S-TRAC was positive

▪ Among ccRCC Pts at high risk for tumor recurrence after nephrectomy, the median DFS was significantly longer in the sunitinib group than in the placebo group (6.8y v 5.6y, HR 0.76, p=.03), at a cost of a higher rate of toxic events (≥3 AEs 63.4% v 21.7%).

Response to Adjuvant Therapy▪ MP25-17: Neutrophil and Platelet to Lymphocyte ratio in S-TRAC Pts (Patel et al)

• N=574 Pts

• SU Pts with baseline NLR <3 had sig longer DFS v. Placebo (median PFS 7.1 v. 4.7 yrs, HR 0.71, P=.02)

• ≥25% decrease in N/PLR at 4 wks was associated with longer DFS v. No change (HR 0.71, p=.01; HR 0.76, p=.05)

• More Pts treated with SU had this change in NLR or PLR (71% and 62% v. 17% and 15%)

• Pts with this N/PLR decrease received higher cumulative SU dose

Take Home Message: Baseline NLR <3 predicted who would benefit from adj SU and ≥25% decrease in N/PLR at 4 wks predicted who better tolerated therapy

Cytoreductive Nephrectomy: CARMENA Inspired

▪ PD03-04: Retrospective study of CN-sunitinib (n=70) v. sunitinib (n=48) found no difference in OS (16.7mo v 15.2mo, p=0.839) (Xu et al)

• IMDC poor risk had worse survival with CN, OS 8.8mo v 9.9mo, p=0.011

▪ MP25-05: Retrospective study of CN-TKI (n=105) v. TKI (n=157) found worse OS in CN-TKI group (p=0.004) (Rink et al)

• 58% MSKCC Intermediate risk

• CN-TKI group younger, > Tstage, higher MSKCC risk, more sarcomatoid

• MVA, CN not an independent predictor of worse outcome

▪ PD03-07: Using CARMENA inclusion criteria, CN in NCDB Pts were younger, less metastatic sites, fewer lung/bone/LN mets than CN arm in CARMENA (Arora et al)

Cytoreductive Nephrectomy: CARMENA Inspired

▪ MP25-13: Kidney Cancer Research Alliance conducted a survey of kidney cancer patients (n=210), informing them of the CARMENA trial result (Battle et al)

• 75% indicated they would still prefer nephrectomy

• 20% with metastatic RCC and tumor in place wanted a nephrectomy

Take Home MessagesCytoreductive Nephrectomy

• Patient selection is key

• Poor risk Pts may be harmed by CN

• Pts that undergo CN in real world datasets are not the same as Pts enrolled in CARMENA

• Balance Pt preferences vs best available evidence

Thank You