Role Of Surveillance In The Managment Of Small Renal Masses

RATIONAL FOR ACTIVE SURVEILLANCE IN SELECTED PATIENTS WITH SMALL RENAL MASSES. Tamer M. Abou Youssif Jan. 10th , 2009

SRMs ?? Small, solid, enhancing and incidentally detected renal cortical masses

Pantuck, A. J., Zisman, A., Belldegrun, A. S.: The changing natural history of renal cell carcinoma. J Urol, 166: 1611, 2001

Cooperberg MR, Kane CJ. Decreasing size at diagnosis of stage 1 renal cell carcinoma: analysis from the National Cancer Data Base, 1993 to 2004. J Urol 2008;179:2131-5.

US Yearly RCC Incidence and Mortality

Ries LAG et al. SEER Cancer Statistics Review, 1975-

50% of SRMs in patients > 65y

OUR TARGET

Ries LAG et al. SEER Cancer Statistics Review, 1975-2004; 2007.

SRMs include*  RCC, all types  Metastasis from other organ  Lymphoma, sarcoma  Infectious mass  Benign tumour  angiomyolipoma, oncocytoma, leiomyoma, fibroma, metanephric adenoma …………. Etc * Renal cysts are not included in SRMs

Risk of benign tumors  70% of the tumors are detected incidentally with a median tumor size of below 4.0 cm.  16.4 -23% of patients following surgical resection of a SRM will have a benign lesion.

Risk of Benign tumors in SRMs Frank et al, 2003 ( a frequently cited article) • 2,770 adult patients who underwent RN or NSS • 376 benign (12.8%) and 2,559 (87.2%) malignant tumors Benign tumors Clear cell RCC High grade RCC

•

Less than 1 cm 43.3%

More than 7 cm 6.3%

25.6%

83%

2.3%

57.7%

98% of RCC tumors less than 1 cm were low grade RCC • The odds of having a malignant compared to a benign tumor ↑ significantly as tumor size ↑ (p 9

Diagnosis of SRMs pathology • With each 1 cm increase there is – 17% increase in the odds of malignancy – 32% increase in the odds of high grade RCC

T size % of benign All 12.8% sizes < 1 cm 46.3% 1-<2 cm 2-<3 cm 3-<4

22.4%

cm 4-<5 cm

9.9%

22% 19.9%

Frank, I., Blute, M. L., Cheville, J. C. et al.: Solid renal tumors: an analysis of pathological features related to tumor size. J Urol, 170: 2217, 2003

10

RADIOLOGIC FEATURES GROWTH RATE

RADIOLOGIC FEATURES • Differentiating benign from malignant renal mass by radiographic or clinical means can be challenging.

Enhancement?? NO

NCCT 3.5 cm mass 39 Hounsfield units

C+CT 68 Hounsfield units.

PATHOLOGY : ONCOCYTOMA

Gross features?? NO

GROWTH RATE • 106 enhancing renal mass • Follow up : 1 yr Growth rate Incidental

Group 1 (Zero GR) 36

-1.4 to 0

Group 2 (Growing) 70

P value

92%

0.48 (0.025 to 1.6) 84%

Surgery

17%

50%

Tumor size

2.9

2.4

0.000 8 0.22

Benign

17%

14%

0.57

0.37

Kunkle DA, Crispen PL, Chen DY, Greenberg RE, Uzzo RG. Enhancing renal masses with zero net growth during active surveillance. J Urol 2007;177:849-53; discussion 53-4.

TUMOR GROWTH PROGRESSION TO METASTATIC DISEASE

Progression to metastatic disease Most significant risk

CURABLE DISEASE BEYOND CURE.

to

DISEASE

• 35 patients with 44 renal masses measuring <4 cm • Average initial tumor dimension was 2.2 cm ( 0.5–4 cm/ year) • Mean follow-up of 47.6 months (6-160month). • Mean GR was 0.21 cm/year (0.03–1.9 cm/ year). • Outcome – 2 (5.7%) were lost to follow-up – 8 (22.9%) underwent surgical resection

Abou Youssif T, Kassouf W, Steinberg J, Aprikian AG, Laplante MP, Tanguay S. Active surveillance for selected patients with renal masses: updated results with long-term follow-up. Cancer 2007;110:1010-4.

PROGRESSION TO METASTATIC DISEASE TWO PATIENTS (5.7%)

Age Initial size Mass # 1

72y 2.7 cm

Mass # 2

66y 2.7 cm

Initial volume

Size Volume growth growth rate follow rate Close up 10.5 cc 0.95 26.3cc cm/yr cc/yr

Onset of Mets

Site of metastasis

40 month

Spinal cord mass

5.75 cc

29 month

0.9 cm/yr 13cc/yr

?? Biopsy

Lung nodules 3 month after Pleural effusion neph

Abou Youssif T, Kassouf W, Steinberg J, Aprikian AG, Laplante MP, Tanguay S. Active surveillance for selected patients with renal masses: updated results with long-term follow-up. Cancer 2007;110:1010-4.

• Clinical decision must balance the risks and likely benefits of both intervention and observation in an individual patient • Best NSS is LEAVING THE WHOLE KIDNEY

NSS  Long-term outcomes approach NSS  5y survival 95-100%  Local recurrence 1-3%

 The excellent results suggest either  Great treatment  OVERTREATMENT.

NSS  Complications

Technical challenge

 Mortality <1%  Adjacent injury <1%  Infection 3%  Fistula/urine leak 510%  ARF 5-10%  2° Haemorrhage 2-3% Excision is an option, but patients must accept risks of surgery and possibility lesion is benign or clinically insignificant

Radio Frequency Ablation (RFA)  high frequency AC causes heat-based tissue damage  Open, laparoscopic or percutaneous  Difficult to monitor procedure with imaging  Exophytic lesions are most suitable

 “heat sink” effect of renal hilum  Impedance monitoring required

RFA Disadvantages    

Incomplete ablation Need for multiple treatments Lack of real-time monitoring Skipping phenomenon : Serious histological concerns about viable tumour within the ablated tumour

Post ablation follow up

Weight CJ, Kaouk JH, Hegarty NJ, Remer EM, Gill IS, Novick AC. Correlation of Radiographic Imaging and Histopathology Following Cryoablation and Radio Frequency Ablation for Renal Tumors. JUROL, Vol. 179, 1277-1283

• • • • • • • •

82 patients with SRMs Management postponed for a median of 14 months (mean, 21 months; range, 6–97 months) The median GR was 0.19 cm/y (mean, 0.30 cm/y; 0.22–1.47 cm/y) Pathology confirmed RCC in 73 of 87 treated tumors (84%). Local disease recurrence was noted in the renal remnant in 1. No systemic recurrences were noted . The estimated 1- and 3-year DFS rates were 100% and 99%, respectively. There were no cancer-related deaths.

Recommendation • The majority of small, sporadic, clinically localized renal tumors will demonstrate a slow growth. • Delayed intervention DOES NOT appear to adversely impact pathological outcomes.

• Don’t rush for surgery for indeterminate SRM especially for – elderly, infirm patient, – central location or technically risky cases. – solitary kidney or bilateral disease

• Imaging alone is inadequate for suggesting the aggressive potential of SRM for both diagnosis and followup. ?? ROLE FOR BIOPSY

Weak points • Active surveillance still lacking follow up guidelines and cutoff values on which intervention could be considered • Tumors 3-4 cm should be excluded – only 5% to 6.5% of tumors 2 to 3 cm – 18.7% to 25.5% of tumors 3 to 4 cm have a high Fuhrman grade (3/4).

• Renal biopsy should be integrated as a diagnostic tool to exclude benign and high grade SRMs from unnecessary follow up.

THE FUTURE …. • G-250 PET Scanning • Molecular imprints for biopsy • Extracorporeal tumor ablation