Renal Cancer Follow-up Counterpoint: Europe

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Series Title Current Clinical Oncology

Chapter Title Renal Cancer Follow-up Counterpoint: Europe Chapter SubTitle

Copyright Year 2013

Copyright Holder Springer Science+Business Media New York

Family Name Antonelli

Particle

Given Name Alessandro

Corresponding Author

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Division Department of Urology

Organization University of Brescia, Spedali Civili Hospital Address Piazzale Spedali Civili 1, Brescia, 25123, Italy

Email alxanto@hotmail.com

Family Name Simeone

Particle

Given Name Claudio

Author

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Division Department of Urology

Organization University of Brescia, Spedali Civili Hospital Address Piazzale Spedali Civili 1, Brescia, 25123, Italy Email

Family Name Cunico

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Given Name Sergio Cosciani

Author

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Division Department of Urology

Organization University of Brescia, Spedali Civili Hospital Address Piazzale Spedali Civili 1, Brescia, 25123, Italy Email

Abstract Despite the significant increase in early diagnoses that took place in recent years, thanks to the increase in popularity of imaging techniques (ultrasonography and CT), the kidney neoplasm is still the urologic cancer with the highest mortality rate [1] due to the significant number of cases with distant metastases for which no systemic treatment with curative potential exists. The disease has a variable and often highly unpredictable biological behavior and recurrence is possible also after radical treatment of organ-confined disease. The most common sites of relapse are lung, adrenal, liver, bone, brain, lumbar fossa, and contralateral kidney, but the literature documents that kidney carcinoma can metastasize to virtually any organ. The absence of effective systemic therapy can justify adoption of the most accurate follow-up plan available to diagnose a relapse as quickly as possible and surgically remove it. As a matter of fact, surgical metastasectomy, wherever technically feasible, can be curative and/or lead to an increase in survival duration [2].

Keywords (separated by

Despite the significant increase in early diagnoses that took place in recent years, thanks to the increase in popularity of imaging techniques (ultrasonography and CT), the kidney neoplasm is still the urologic cancer with the highest mortal-ity rate [1] due to the significant number of cases with distant metastases for which no systemic treatment with curative potential exists. The disease has a variable and often highly unpredictable biological behavior and recurrence is possible also after radical treatment of organ-confined disease. The most common sites of relapse are lung, adrenal, liver, bone, brain, lumbar fossa, and contralateral kidney, but the litera-ture documents that kidney carcinoma can metastasize to virtually any organ. The absence of effective systemic ther-apy can justify adoption of the most accurate follow-up plan available to diagnose a relapse as quickly as possible and surgically remove it. As a matter of fact, surgical metastasec-tomy, wherever technically feasible, can be curative and/or lead to an increase in survival duration [2].

Several clinical, biochemical, anatomic pathological, and molecular factors have been analyzed for their prognostic value but today anatomic pathological staging according to the TNM system remains the most important single prognos-tic factor. In order to increase its accuracy, several authors have proposed some integrated staging systems in which the TNM stage is combined with other prognostic factors [3].

In our institution, over the last two decades, we have sur-gically treated more than 1,500 patients with renal cell carci-noma. In cases where radical surgery was applied to a nonmetastatic neoplasm (pN0/Nx M0), patients are followed

with a surveillance plan independent of the disease stage. Periodic controls are done with blood tests (complete blood count, kidney and liver function tests), abdominal imaging examinations (ultrasonography or CT) and chest examina-tions (plain X-rays or CT) once each 6 months in the first 2 years after surgery and then again every year for an indefinite time. Additional examinations (brain CT and bone scintigra-phy) have been, in general, used only in the presence of specific symptoms. In light of this experience, which has allowed us to monitor these patients continuously, we have recently reviewed the results obtained and retrospectively applied an integrated staging system to assess which cases might require more intense surveillance and which cases might well be served by less intense surveillance [4].

Among the many integrated staging systems available, we have chosen the one developed at UCLA (UCLA Integrated Staging System, UISS [5]), which is based on two anatomic pathological factors (the stage according to TNM 1997 [6] and the cytonuclear grading according to Fuhrman [7]) plus a clinical factor (the performance status as defined by the ECOG score [8]) (see Table 74.1). The widespread availabil-ity of this information makes this staging system applicable in all institutions, which is one of its greatest assets. The combination of the three factors permits assignment to three risk classes, i.e., low risk (LR), intermediate risk (IR), and high risk (HR) (see Table 74.2).

We have reviewed data on 814 patients with nonmeta-static kidney cancer (pN0/Nx M0), 158 of which had under-gone nephron-sparing surgery, the remaining 656 had undergone nephrectomy. Average follow-up duration for all patients was 76 months (minimum 24 months). Relapses have occurred in 193 cases, corresponding to 24% of the total. According to UISS, 140 cases were LR, 420 IR, and 254 HR. Relapse rate in the follow-up for the three risk

Keywords

Nonmetastatic kidney cancer • Kidney • Nephrectomy • Surveillance • Papillary carcinoma

Renal Cancer Follow-up

Counterpoint: Europe

Alessandro Antonelli, Claudio Simeone, and Sergio

Cosciani Cunico

74

A. Antonelli (*) • C. Simeone • S.C. Cunico

Department of Urology, University of Brescia, Spedali Civili Hospital, Piazzale Spedali Civili 1, Brescia 25123, Italy

e-mail: alxanto@hotmail.com

F.E. Johnson et al. (eds.), Patient Surveillance After Cancer Treatment, Current Clinical Oncology, DOI 10.1007/978-1-60327-969-7_74, © Springer Science+Business Media New York 2013

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A. Antonelli et al.

classes was 10, 22, and 54%, respectively, with an average latency after surgery of 54, 36, and 30 months, respectively. The most common type of relapse was distant metastasis (73%), followed by local relapse (12%) and by the appear-ance of a new kidney neoplasm in the contralateral kidney (11%) or in the remaining kidney after nephron-sparing surgery (4%). Table 74.3 shows the distribution of relapses, with onset times, in the different UISS risk classes. It is

easy to note that the risk of relapse via a new renal neo-plasm decreases gradually over time among the three risk classes (LR, IR, and HR) while the chance of local relapse or distant metastasis increases from LR to IR to HR class. From a biological point of view relapses in the kidney deserve to be viewed and dealt with differently from distant metastases or local relapses. Indeed, the development of a neoplasm in the kidney undergoing nephron-sparing sur-gery may be explained by the presence of unrecognized multifocal disease or by the lack of adequate surgical mar-gins while a neoplasm in the contralateral kidney can be considered a new primary cancer. Patients with a relapse in the contralateral kidney, in the ipsilateral kidney after nephron-sparing surgery, with distant metastasis, and local recurrence have a 12-month survival rate after diagnosis of 96, 86, 70, and 44%, respectively. Figures 74.1 and 74.2 show the time distribution of the three risk classes of relapses in the chest and in the abdomen, including abdom-inal metastases, local relapses, and kidney relapses. Disease relapse in LR patients in the first 5 years of follow-up occurs chiefly at abdominal level, while the risk of lung recurrence is less serious. On the other hand, IR patients in the first 5 years after surgery have a higher risk of relapse in the lung, especially in the first 24–36 months, while risk of relapse in the abdomen is lower; the same happens, albeit at a significantly lower rate, for the subsequent 5 years. HR patients, during the earliest years of follow-up, show a high risk of relapse in the abdomen and a lower risk of lung metastasis. This risk, though still significant, decreases in the subsequent 5 years. All risk classes, after 10 years of follow-up, feature only rare relapses, chiefly in the abdomi-nal area and in the contralateral kidney. As regards the imaging methods to be used for monitoring the chest and abdomen, from a cost/benefit point of view, it is preferable

Table 74.1 Prognostic systems

TNM 1997

pT1 Tumor <= 7 cm in the greatest dimension, limited to the kidney

pT2 Tumor >7 cm in the greatest dimension, limited to the kidney

pT3 Tumor extends into major veins or directly invades the adrenal gland or perinephric fat tissues but not beyond the Gerota’s fascia

pT4 Tumor directly invades beyond Gerota’s fascia Fuhrman’s grading

G1 Tumor cells with small (~10 mm) round uniform nuclei without nucleoli

G2 Tumor cells with larger nuclei (~15 mm) with irregularities in outline nucleoli when examined under high power (400) G3 Tumor cells with even larger nuclei (~20 mm) with obvi-ously irregular outline prominent larger nucleoli even at low power (100)

G4 Tumor cells with bizarre, multilobed nuclei heavy clumps of chromatin

ECOG score

0 Fully active, able to carry on all predisease performance without restriction

1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work

2 Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours

3 Capable of only limited self-care, confined to bed or chair more than 50% of waking hours

4 Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair

Table 74.2 UISS definitions

UISS risk class pT G ECOG

Low risk 1 1–2 0 Intermediate risk 1 1–2 >0 1 3–4 Any 2 Any Any 3 1 Any 3 >1 0 High risk 3 >1 >0 4 Any Any

Table 74.3 Site of relapse

latency (months) All patients (%) LR (%) IR (%) HR (%) Operated kidney 23.4 4.1 11.6 5.4 0 Contralateral kidney 71.8 10.9 30.1 10.1 4.0 Local recurrence 26.4 11.9 3.9 7.6 20.0 Distant metastasis 29.5 73.0 53.8 76.1 76.0 Abdomen 32.8 15.6 7.2 17.1 15.8 Chest 29.5 48.3 35.7 50.0 49.1 Bone 14.9 11.3 21.4 12.9 7.0 Others 41.4 9.9 21.4 8.6 8.8 Multiple sites 24.1 14.9 14.3 11.4 19.3 Recurrence sites and time, as a percentage of asymptomatic patients, and the distribution of different types of recurrence in UISS risk groups (LR low risk, IR intermediate risk, HR high risk; the sum of percent-ages of each site of distant metastasis is 100%)

70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 t1.1 t1.2 t1.3 t1.4 t1.5 t1.6 t1.7 t1.8 t1.9 t1.10 t1.11 t1.12 t1.13 t1.14 t1.15 t1.16 t1.17 t1.18 t1.19 t1.20 t1.21 t1.22 t1.23 t1.24 t1.25 t1.26 t1.27 t1.28 t1.29 t1.30 t1.31 t1.32 t1.33 t2.1 t2.2 t2.3 t2.4 t2.5 t2.6 t2.7 t2.8 t2.9 t2.10 t3.1 t3.2 t3.3 t3.4 t3.5 t3.6 t3.7 t3.8 t3.9 t3.10 t3.11 t3.12 t3.13 t3.14 t3.15 t3.16

Fig. 74.1 Time distribution of thoracic relapses (LR low risk, IR intermediate risk, HR high risk; marks represent the events of recurrence as

percentiles on overall recurrences in each specific site; zero point is the time of treatment of primary tumor)

to use cheaper and safer (for the patient) techniques like abdominal ultrasonography and chest radiography for lower-risk patients, using CT only for higher-risk patients. The risk of bone metastases is limited. It is higher in the time period closer to the surgery and it also pertains chiefly to HR cases. In light of these data, we think it is possible to offer different surveillance plans, depending on risk classes, as shown in Tables 74.4, 74.5, 74.6.

There is no significant difference in risk and relapse mode between patients subjected to nephrectomy and those sub-jected to nephron-sparing surgery. There is consequently no need to modify surveillance according to this factor.

One factor not included in the UISS but, in our opinion, worthy of consideration is the tumor histological subtype. Currently, according to the classification drafted in the Heidelberg and Rochester consensus conferences, there are four main histological subtype of kidney carcinoma: clear

cell (80% of cases), papillary (in turn divided in type 1 and type 2), chromophobe, and collecting duct [9]. Although the independent prognostic role of the histotype has not been clearly demonstrated, it is quite evident that patients suffer-ing with chromophobe and type 1 papillary renal cell carci-nomas usually have a highly favorable prognosis, whereas patients with collecting duct carcinoma have an extremely unfavorable prognosis and the prognosis of patients with type 2 papillary carcinoma or conventional renal cell carci-noma is somewhere in between the extremes [10, 11]. Consequently, we propose to manage follow-up of patients with favorable histotype (chromophobe and type 1 papillary renal cell carcinoma) with the plan proposed for LR class patients and to apply the HR follow-up plan for patients with the unfavorable histotype (collecting duct carcinoma). The follow-up of patients with type 2 papillary carcinoma can be decided by stratification with the UISS.

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Table 74.4 Surveillance after curative-intent treatment for renal

cancer for LR patients at Spedali Civili Hospital years posttreatment 1 2 3 4 5 5–10 >10 Chest X-ray 0 1 0 1 0 0 0 Abdomen US 1 1 1 1 1 2 1 Abdomen CT 0 0 0 0 0 0 0 Chest CT 0 0 0 0 0 0 0 Bone scan 0 0 0 0 0 0 0

The number in each cell is the number of times a particular examination is recommended in a particular posttreatment year (LR, low risk)

Fig. 74.2 Time distribution of abdominal relapses (LR low risk, IR intermediate risk, HR high risk; marks represent the events of recurrence as

percentiles on overall recurrences in each specific site; zero point is the time of treatment of primary tumor)

Table 74.5 Surveillance after curative-intent treatment for renal

cancer for IR patients at Spedali Civili Hospital years posttreatment 1 2 3 4 5 5–10 >10 Chest X-ray 1 1 2 1 1 5 0 Abdomen US 1 1 2 1 1 5 1 Abdomen CT 1 1 0 0 0 0 0 Chest CT 1 1 0 0 0 0 0 Bone scan 0 0 0 0 0 0 0

The number in each cell is the number of times a particular examination is recommended in a particular posttreatment year (IR intermediate risk)

Table 74.6 Surveillance after curative-intent treatment for renal

cancer for HR patients at Spedali Civili Hospital years posttreatment 1 2 3 4 5 5–10 >10 Chest X-ray 0 1 1 2 2 5 0 Abdomen US 0 1 1 2 2 5 1 Abdomen CT 2 1 1 0 0 0 0 Chest CT 2 1 1 0 0 0 0 Bone scan 0 1 0 0 0 0 0

The number in each cell is the number of times a particular examination is recommended in a particular posttreatment year (HR high risk)

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