Management of the Incidental Management of the Incidental Renal MassRenal Mass

Lee N. Hammontree, M.D.

Urology Centers of AlabamaBirmingham, Alabama

Key ConsiderationsKey Considerations

What are the indications for active surveillance

What is the risk of progressionWhen will it metastasize (Natural History)What is the risk of observationWhat is the optimal F/U regimen?

Indications for active Indications for active surveillancesurveillance

Absolute – Not surgical candidates due to severe comormidities

Relative – Chronic stable comorbidities Elective

– Pt wishes for period of observation due to small size of renal mass

ObservationObservation

110 Patients > 75 years of age (Median 81 years old)

Size Variable

Mean tumor growth – 0.28 CC/YR

43% no tumor growth at 29 months

Four patients progressed RX’D

31% Died…..None from Renal Cell Cancer

Novick JU 2008, 180:505

Malignancy RiskMalignancy Risk

2770 sporatic unilateral nonmetastatic solid renal tumors

1970-2000Reviewed by single pathologistCorrelation to size

Frank, et al 2003

Histologic Subtypes for benign Histologic Subtypes for benign and RCC tumorsand RCC tumors

Benign

Oncocytoma Angiomyolipoma Papillary Adenoma Not otherwise specified Metanephric adenoma

Number of tumors (%)

274 (72.9) 67 (17.8) 16 (4.3) 14 (3.7) 5 (1.3)

There were 376 benign (12.8%) and 2,559 (87.2%) malignant tumors.

Proportion of benign to RCC Proportion of benign to RCC tumors based on sizetumors based on size

Tumor size (cm) 0.0- less than 1.0 1.0- less than 2.0 2.0- less than 3.0 3.0- less than 4.0 4.0- less than 5.0 5.0- less than 6.0 6.0- less than 7.0 7.0 or greater

No. Benign (%) 37 (46.3) 38 (22.4) 75 (22.0) 71 (19.9) 37 (9.9) 40 (13.0) 11 (4.5) 67 (6.3)

No. RCC (%)

43 (53.8)132 (77.7)266 (78.8)285 (80.1)336 (90.1)267 (87.0)232 (95.5)998 (93.7)

Bigger tumor = More likely malignant

Role of Percutaneous Bx?Role of Percutaneous Bx?

Indications– Suspected metastasis– Suspected lymphoma– Suspected abscess

Cons– Seeding tract?– unreliability

Percutaneous biopsy?Percutaneous biopsy?

Sampling error is major problem– Non diagnostic specimens ~ 20%– Predictors of non diagnostic specimen

Tumor size (<3cm 37%) Number and size of cores Experience of cytopathologist Presence of cystic components

– Oncocytomas (30% may actually be RCC)

Percutaneous biopsy?Percutaneous biopsy?

Issue of tract seeding– Only 1 reported case: Shenoy et al, 1991

Biopsy is of limited value in determining malignancy risk

Risk of Tumor GrowthRisk of Tumor Growth

Growth rate of RCC vs Benign is unknown9 single institution studies

– 234 lesion meta-analysis– Mean size at presentation = 2.6cm (1.73-4.08)– Mean follow-up = 34 months– Mean growth rate = 0.28cm/year (0.09-0.86)

Chawla, JU Feb 2006

Risk of Tumor GrowthRisk of Tumor Growth

No difference in growth rate based on size of initial presentation

No difference in growth rates between oncocytoma and RCC

No growth = benign

Chawla, JU Feb 2006

Risk of MetastasisRisk of Metastasis

Chawla Meta-analysis of Observational studies:– 3/286 had mets in avg. 34mo follow up

2/3 were tumors > 8cm, other not reported One had slow growth (0.2cm/yr) other rapid (1.3cm/yr)

Bell’s autopsy-based data (1938-1950)– 3/62 tumors < 3cm metastasized (~5%)– 70/106 tumors >3cm metastasized

Risk of MetastasisRisk of Metastasis

Duffey et al, JU 2004– 181 patients with VHL– 108 patients with tumors < 3cm followed until

tumor reached 3cm (then treatment)– 73 patients with tumors >3cm definitive Rx

Risk of MetastasisRisk of Metastasis

Duffey 2004– Of the 108 < 3cm

Mean F/U 58.1 months 71 (66%) went on to surgery due to growth No metastasis within the follow up period

– Of the 73 > 3cm Mean follow up 72.9 months 20 (27.4) developed mets

Risk of Observation / Delayed Risk of Observation / Delayed InterventionIntervention

Development of Symptoms– Poorly reported in observational series– Chawla: 5 reported cases of gross hematuria

Metastasis– Chawla: 3/286 cases (were large tumors)– No published cases of incidental small masses

that have progressed to mets during observation (Rendon & Jewett, Uro Onc 24:62, 2006)

Surveillance RegimenSurveillance Regimen

Same imaging modality (CT or MRI)Consistency in location of measurementBest to review films yourselfImaging q 3-6 months x 2 years then yearly

if stable

Small Renal MassSmall Renal Mass

Do we need to remove the entire kidney?

▪ Cancer specific survival

Should we remove the entire kidney?

▪ Long term renal function

Renal Cell CancerRenal Cell Cancer

Incidence - 2007

51,190 Cases

pT1a (<4cm) = 48-66%

5 year survival is 95%

Radical nephrectomy vs. Partial Radical nephrectomy vs. Partial nephrectomynephrectomy

Cancer specific survival:

MSK Series

252 patients < 4 cm

189 Radical

79 Partial

95% CA Specific Survival (40 mos.)

Radical = PartialJU 2000, 163:730

Indications for Partial Indications for Partial NephrectomyNephrectomy

Bilateral Tumors Solitary Kidney Contralateral kidney at risk

– Heriditary RCC– Medical renal disease– Stones– Chronic pyelonephritis– VUR– Diabetes Melletis

Exophytic mass <4cm with normal contralateral Expanding indications….

Survival: Radical vs PartialSurvival: Radical vs Partial

327 Patients < 65 years old

10 year survival (OVERALL)

Radical Nephrectomy 82%

Partial Nephrectomy 93%

CKD (not on dialysis)

Anemia, Osteoporosis, CV Mortality

Mayo Clinic JU 2008, 179:468

Development of Chronic Renal DiseaseDevelopment of Chronic Renal Disease

Lancet Oncology. 2006, 7:735 MSK

662 PTS 1989 – 2005

RX: RN 81% PN 19%

3 year risk of CKD (III) GFR < 60 CC/MIN

65% Radical

20% Partial

Pre-Op GFR > 60 CC

New onset GFR < 45 CC

RN 43% PN 7%

26% had Pre-Op GFR < 60 CC/MIN

Difference from Renal DonorsDifference from Renal Donors

Nephrectomy (Tumor)GFR 69 CC/MIN Average age…58

Donor NephrectomyGFR 92 – 103 CC/MIN Average age…50

Small Renal MassSmall Renal Mass

Options for Renal Preservation1. Observation

2. Partial Nephrectomy (Open, Lap, Haln, and Robotic)

3. Cryo Ablation (Open, Lap, and Percutaneous)

4. Radiofrequency Ablation (RFA) (Open, Lap, Percutaneous)

Small Renal Mass – RX OptionsSmall Renal Mass – RX Options

Meta – Analysis 1980 – 2006

RX Modality Number StudiesNumber Tumor

PN 50 5037 (78%)

Cryo 19 496 (8%)

RFA 21 607 (9%)

Surveillance 10 331 (5%)

UZZO JU 2008, 179:1227

PathologyPathology

Renal Cell Cancer 79.7%

Benign 12.2%

Unknown 8.1%

Local Recurrence

RN 3.7% 226/6140

PN 2.6% (132/5037)

Cryo 4.6% (23/496)

RFA 11.7% (71/607)

Progress to MetsProgress to Mets

RX Options Number F/U (Months)

PN 281/5037 5.6% 54

Cryo 6/496 1.2% 18

RFA 14/607 2.3 16

Observation 3/331 0.9% 33

Renal Cryoablation Patient Renal Cryoablation Patient SelectionSelection

Candidate for laparoscopic or open partial Nephrectomy

Exophytic Mass < or =4 cmSolitary kidneyMultiple lesionsRenal failureComorbidity putting renal function at risk

Laparoscopic Cryoablation: Laparoscopic Cryoablation: Ultrasound MonitoringUltrasound Monitoring

Survey of the kidney and assessment of tumor size

Ultrasound visualization across the kidney is essential to monitor the full extent of the iceball

Monitor in real-time to confirm total coverage of lesion + margin

Freeze Test Each ProbeFreeze Test Each Probe

To ensure each CryoProbe will

function properly they must be tested in a basin of sterile

water or saline before placement in

patient

Laparoscopic Renal Laparoscopic Renal CryoablationCryoablation

Intraoperative Real Time UltrasoundIntraoperative Real Time Ultrasound

Dedicated articulating laparoscopic transducer Place transducer crystal on kidney surface opposite lesion Survey treatment progress through normal renal tissue

Ice Ball FormationIce Ball FormationEdge of Ice Ball

Acoustic Shadow

August 2006

March 2007

September 2007

September 2008

Comparison of Partial Comparison of Partial Nephrectomy Nephrectomy

and Cryoablation and Cryoablation References: References:

For Partial Nephrectomy: For Partial Nephrectomy:

All studies quoted in Campbell’s Urology Table 75-15: All studies quoted in Campbell’s Urology Table 75-15: ““Results of nephron Sparing surgery for renal cell Results of nephron Sparing surgery for renal cell

carcinoma”carcinoma”Study Sizes: 10 – 485 patients, Mean follow-up: 24 – 75 monthsStudy Sizes: 10 – 485 patients, Mean follow-up: 24 – 75 months

For Cryoablation: For Cryoablation: Series Reference No. Pts. Mean F/u (mo)

Hegarty Urology 2006 161 36

Davol Urology 2006 72 64

Lawatsch Journal of Urology 2006 59 24.5

Hegarty 2006 AUA 60 72

Gill Journal of Urology 2005 56 43

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2020

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Partial Nephrectomy Partial Nephrectomy CryoablationCryoablation

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Cryo vs. Partial Nephrectomy: Cancer Specific SurvivalCryo vs. Partial Nephrectomy: Cancer Specific Survival

1. Andrew C. Novick and Steven C. Campbell. Renal Tumors. In: Campbell’s Urology 8th Edition 2. Nicholas J. Hegarty, et al. 2006 Jul;68(1 Suppl):7-13. 3. Patrick E. Davol, et al. Urology. 2006 Jul;68(1 Suppl):2-6. 4. Lawatsch EJ, et al. J Urol. 2006 Apr;175(4):1225-9. 5. Nicholas J Hegarty, et al. Presented at the 2006 Annual Meeting of the American Urological Association, May 20-25, 2006, Atlanta Georgia 6. Gill IS, et al. J Urol. 2005 Jun;173(6):1903-7.

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Partial Nephrectomy Partial Nephrectomy CryoablationCryoablation

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Cryo vs. Partial Nephrectomy: LocalCryo vs. Partial Nephrectomy: Local Recurrence RateRecurrence Rate

1. Andrew C. Novick and Steven C. Campbell. Renal Tumors. In: Campbell’s Urology 8th Edition 2. Nicholas J. Hegarty, et al. 2006 Jul;68(1 Suppl):7-13. 3. Patrick E. Davol, et al. Urology. 2006 Jul;68(1 Suppl):2-6. 4. Lawatsch EJ, et al. J Urol. 2006 Apr;175(4):1225-9. 5. Nicholas J Hegarty, et al. Presented at the 2006 Annual Meeting of the American Urological Association, May 20-25, 2006, Atlanta Georgia 6. Gill IS, et al. J Urol. 2005 Jun;173(6):1903-7.

Risks of metastasisRisks of metastasis

99 studies representing 6,471 lesions were analyzed.

No statistical differences were detected in the incidence of metastatic progression regardless of whether lesions were excised, ablated or observed.

Excise, Ablate or Observe: The Small Renal Mass Dilemma—A Meta-Analysis and ReviewKunkle, et all JU, 2008

Cryoablation series, UCACryoablation series, UCA

Single surgeon (LH)208 cases since July 2006-November 20101 local recurrence (0.5%) (4cm +)

– Treated with repeat cryoablation 2 years later

All were laparoscopic (45% extraperitoneal approach)

4 patients with metastatic disease (1.9%)T1a tumors

FireFly™FireFly™ Fluorescence Fluorescence Imaging for the Imaging for the da Vincida Vinci®® Si Si

In service GuideIn service Guide

BILITRANSLOCASE (BTL) IS IMMUNOLOCALISED IN PROXIMAL AND DISTAL RENAL TUBULES AND ABSENT IN RENAL CORTICAL TUMORS ACCURATELY CORRESPONDING TO INTRAOPERATIVE NEAR INFRARED FLUORESCENCE (NIRF) EXPRESSION OF RENAL CORTICAL TUMORS USING INTRAVENOUS INDOCYANINE GREEN (ICG)

Dragan J Golijanin*, Jonah Marshall, Allison Cardin, Eric A Singer, Ronald W Wood, Jay E Reeder, Guan Wu, Jorge L Yao, Sabina Passamonti, Edward M Messing. Rochester, NY, and Trieste, Italy.

JU May, 2008

ICGICG

Conclusion: This is the first study to show that ICG and bilotranslocase are uniformly present in normal parenchyma and benign tumors but differentially downregulated in renal cortical tumors. ……… this may explain the non or hypo fluorescence of renal cortical tumors observed intraoperatively with near infrared imaging.