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EUROPEAN UROLOGY 57 (2010) 112122

available at www.sciencedirect.com journal homepage: www.europeanurology.com

Kidney Cancer

Factors Predicting Health-Related Quality of Life Recovery in Patients Undergoing Surgical Treatment for Renal Tumors: Prospective Evaluation Using the RAND SF-36 Health Survey
Giacomo Novara, Silvia Secco, Maria Botteri, Vincenzo De Marco, Walter Artibani, Vincenzo Ficarra *
Department of Oncological and Surgical Sciences, Urologic Clinic, University of Padua, Padua, Italy

Article info Article history: Accepted April 8, 2009 Published online ahead of print on April 21, 2009 Keywords: Kidney neoplasms Renal cell carcinoma Health-related quality of life SF-36 Radical nephrectomy Partial nephrectomy Nephron-sparing surgery

Abstract
Background: Most newly diagnosed kidney cancers present at localized stages. With appropriate treatments, the cancer-specific survival rates of such patients are extremely high, which makes patients health-related quality of life (HRQoL) a relevant issue. To date, most of the available studies on HRQoL have been biased by the absence of baseline HRQoL assessments and by retrospective designs. Objective: To evaluate the baseline HRQoL of patients with kidney cancer, comparative HRQoL during the rst year after surgery, and the prognostic factors predictive of HRQoL recovery. Design, setting, and participants: We prospectively collected the data of all patients undergoing surgery for kidney tumors at a tertiary academic referral center from February 2006 to September 2007. Interventions: Patients underwent nephron-sparing surgery (NSS) or radical nephrectomy (RN). Measurements: Patients were invited to self-complete the validated, Italian version of the RAND 36-Item Health Survey 1.0 (SF-36) before surgery, 6 mo after surgery, and 12 mo after surgery. Results and limitations: Overall, 129 consecutive patients were evaluated. No signicant differences were found between the baseline scores of our patients and age- and sexmatched normative data for the Italian general population. Comparing the baseline SF-36 scores to those at 6 mo and 12 mo, there was statistically signicant worsening in the physical domains and improvement in the emotional domains (all p < 0.05). About 5080% of patients returned to baseline scores 6 mo and 12 mo after surgery. Age, body mass index (BMI), educational level, occupational status, New York Heart Association (NYHA) functional class, tumor mode of presentation, pathologic stage, size, and histologic subtype were associated with 6-mo and 12-mo return to the baseline HRQoL scores. The main limitation of the study was the lack of a disease-specic questionnaire. Conclusions: Most patients returned to preoperative HRQoL within 12 mo after RN or NSS. Several patient features, clinical variables, and pathologic tumor variables predict the return of HRQoL.

# 2009 Published by Elsevier B.V. on behalf of European Association of Urology.

* Corresponding author. Department of Oncological and Surgical Sciences, Urologic Clinic, University of Padua, Monoblocco Ospedaliero, 4th oor, Via Giustiniani 2, 35100 Padua, Italy. Tel. +39 0498212720; Fax: +39 0498218757. E-mail address: vincenzo.carra@unipd.it (V. Ficarra). 0302-2838/$ see back matter # 2009 Published by Elsevier B.V. on behalf of European Association of Urology. doi:10.1016/j.eururo.2009.04.023

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1.

Introduction

An estimated 54 000 new cases of kidney cancer were diagnosed in the United States in 2008 [1]. Similarly, about 64 000 new cases were diagnosed in Europe in 2006 [2]. However, a great proportion of newly diagnosed patients currently present with stage I tumors, incidentally detected cancer [3] that can be treated appropriately by elective partial or radical nephrectomy (RN), yielding extremely high cancer-specific survival rates. The World Health Organization defines quality of life as an individuals perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns [4]. Consequently, quality of life is a multidimensional, broad-ranging concept comprising individuals perceived physical, psychosocial, and emotional functioning, which is affected by their physical health, psychological state, level of independence, social relationships, and their relationship to the salient features of their environment. Specifically, health-related quality of life (HRQoL) is the extent to which ones usual or expected physical, emotional, and social well-being are affected by a medical condition or its treatment [5]. Due to the multidimensional nature of HRQoL and the complexity of measuring it, a large spectrum of questionnaires and scales have been developed, including generic and disease-specific questionnaires, and even scales specific for different cancer sites [6]. Few authors have reported HRQoL after surgical treatment of kidney tumors [713]. However, most studies have been biased by several issues, including absence of a baseline HRQoL assessment, cross-sectional design [713], small number of enrolled patients [10,13], and low response rates [10,11]. Consequently, factors affecting the baseline HRQoL of patients with renal tumors have not been evaluated, and the time needed to return to baseline HRQoL after treatment and prognostic factors predictive of the return to the preoperative HRQoL are mostly unknown. To date, HRQoL issues have had only a marginal impact on the decision-making process of those patients with kidney tumors. The present study had the following objectives: (1) to prospectively evaluate the baseline HRQoL of patients with kidney tumors in comparison to the healthy population, (2) to evaluate changes in HRQoL during the first 12 mo after nephron-sparing surgery (NSS) or RN, and (3) to evaluate the factors predictive of the return of HRQoL. 2. Materials and methods

assess the performance status, cardiovascular risk, and comorbidity of the patients. Patient symptoms were categorized according to the Patard classification [19]. The Heidelberg classification [20] was used to assign histologic tumor subtype. Pathologic stage and nuclear grade were assigned according to the 2002 version of the TNM staging system [21] and Fuhrman grading system [22]. With regard to surgical techniques, transperitoneal RN (using either an open or a laparoscopic approach) and NSS through a flank incision using an extraperitoneal approach were usually performed. The indications for elective and imperative NSS were those standardized in the literature and those summarized in the EAU guidelines [14]. We used the validated, Italian version of the RAND 36Item Health Survey 1.0 (SF-36) [23,24] to evaluate generic aspects of HRQoL. The SF-36 consists of 36 multiple-choice questions measuring eight distinct domains: physical function (PF), role limitations due to physical health problems (RP), bodily pain (BP), general health perception (GHP), emotional well-being (EWB), role limitations due to emotional problems (RE), energy/fatigue (EF), and social function (SF). Scores for each scale range from 0100, with higher scores indicating higher function or wellbeing [23]. The patients received the HRQoL questionnaire the morning before the operation to be completed through confidential self-administration and returned before surgery and 6 mo, 12 mo, and 24 mo afterward. All patients who did not return the follow-up questionnaires in time were reminded by telephone 2 wk after each deadline. The present paper evaluated the patients at 12-mo follow-up.
2.1. Statistical analysis

From February 2006 to September 2007, all patients undergoing NSS or RN for kidney tumor in our department were invited to participate in this study. All cases were preoperatively staged as recommended by European Association of Urology (EAU) guidelines [14]. Eastern Cooperative Oncology Group (ECOG) classification [15], Charlson comorbidity index [16,17], and New York Heart Association (NYHA) classification [18] were used to

Continuous, normally distributed variables are reported as the mean value plus or minus standard deviation (SD). Continuous non-normal variables are presented as the median values and interquartile ranges. Z scores were used to compare patients with age- and sex-matched normative data for the Italian general population [24]. Specifically, a patient was considered to have scores similar to those of the normative data if mean scores for each domain were within 1 SD of age- and sexmatched normative data [10]. Patients were considered to have returned to the baseline value when the follow-up score returned to within 10 points of the score recorded before treatment on a particular scale [25,26]. The Mann-Whitney U-test, Wilcoxon signed-rank test, Friedman test, and Pearson chi-square test were used to compare continuous and categorical variables, as appropriate. In univariate analyses, the patients with scores returning to the baseline value were censored. Logistic regression analyses were used to identify the independent prognostic factors predictive of recovering baseline scores. All analyses showed statistical significance, with twotailed p values of < 0.05. All data were analyzed with the Statistical Package for Social Sciences v.16.0 (SPSS Inc, Chicago, IL, USA).

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3.

Results

Table 1 (Continued ) Variable Cases (%)

Overall, 168 patients had surgery for kidney tumors during the evaluation period; 151 (90%) decided to participate,
Table 1 Clinical and pathologic characteristics of the 129 patients enrolled in the study Variable
Gender Male Female Age (mean and standard deviation) BMI (median and IQR) Marital status Married Not married Years of education 8 >8 Occupation Full-time employed Not employed Prior history of other cancers ECOG Performance Status 0 !1 Charlson score (median and IQR) NYHA class 1 2 34 ASA class 1 2 3 4 Mode of presentation Incidental Symptomatic Clinical tumor size (median and IQR) Clinical stage of the primary tumor (TNM, 2002) cT1a cT1b cT2 cT3a cT3bc Clinical N0 stage (TNM, 2002) Clinical M0 stage (TNM, 2002) Preoperative Hb level (g/l) (mean and standard deviation) Preoperative creatinine level (mmol/l) (median and IQR) Surgery Open radical nephrectomy Laparoscopic radical nephrectomy Elective partial nephrectomy Imperative partial nephrectomy Pathological tumor size (median and IQR) Histological subtypes Benign tumors Renal cell carcinoma

Cases (%)

Pathological stage of the primary tumor (TNM, 2002) pT1a pT1b pT2 pT3a pT3bc/pT4 Pathological stage of lymph node (TNM, 2002) pNx pN01 (1) pN1 Status at follow-up Alive and disease free Alive with disease progression Death of cancer

57 (52) 24 (22) 10 (9) 5 (4) 15 (14)

81 (63) 48 (37) 61.3 12.4 25.9 (23.728)

96 (74) 32 (25) 1 (1)

124 (96) 4 (3) 1 (1)

98 (76) 31 (24)

73 (57) 56 (43)

BMI = body mass index; IQR = interquartile range; ECOG = Eastern Cooperative Oncology Group; NYHA = New York Heart Association; ASA = American Society of Anesthesiologists; TNM = tumor, node, metastasis; Hb = hemoglobin.

67 (52) 62 (48) 18 (14)

117 (91) 12 (9) 0 (01)

115 (89) 12 (9) 2 (2)

29 (22) 61 (47) 37 (29) 2 (2)

105 (81) 24 (19) 4 (2.56)

67 (52) 28 (22) 19 (15) 7 (5) 8 (6) 127 (98) 121 (94) 13.9 1.7

while 17 (10%) refused. Twenty-two of the 151 patients (15%) were excluded from the present analysis because of the lack of the follow-up questionnaires. The responses of the remaining 129 patients (85%) who completed the 6-mo and 12-mo questionnaires were evaluated. The clinical and pathologic characteristics of the patients who responded and who did not were significantly different with regard to clinical and pathologic TNM stages. Specifically, patients who did not respond showed higher percentages of unfavorable clinical and pathologic features and experienced a significantly higher rate of cancer-related deaths, with only 1 of 129 responders (0.8%) and 8 of 22 nonresponders (36.4%) dying of cancer ( p < 0.001). Table 1 summarizes the clinical and pathologic characteristics of the patients enrolled in the study. Table 2 presents the SF-36 scores for our cohort of patients as a whole and the z score comparing the sample with the ageand sex-matched normative data from the Italian general population. The mean baseline scores for each domain were within 1 SD of age- and sex-matched normative data for the Italian general population, indicating no significant differences between the general population and our cohort.

Table 2 Baseline SF-36 scores for our cohort of patients and the z-score comparing the sample with the age- and sex-matched normative data from the Italian general population [24] Baseline scores
PF RP BP GHP EWB RE EF SF

Mean SD
78.9 27 67.2 41.4 86.1 43.6 59.9 19.8 59.8 24.1 52.6 41.4 60.3 21.4 64.9 24.3

Mean z score
0.24 0.15 0.64 0.09 0.21 0.61 0.80 0.24

89 (75104)

51 (40) 13 (10) 57 (44) 8 (6) 4 (36)

20 (15) 109 (85)

PF = physical function; RP = role limitations due to physical health problems; BP = bodily pain; GHP = general health perception; EWB = emotional well-being; RE = role limitations due to emotional problems; EF = energy/fatigue; SF = social function.

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Table 3 SF-36 score variation in the different scales during the follow-up (median and interquartile range [IQR]) SF-36 domain
Physical function Wilcoxon signed-rank test p value Role limitations due to physical health problems Wilcoxon signed-rank test p value Bodily pain Wilcoxon signed-rank test p value General health perception Wilcoxon signed-rank test p value Emotional well being Wilcoxon signed-rank test p value Role limitations due to emotional problems Wilcoxon signed-rank test p value Energy/fatigue Wilcoxon signed-rank test p value Social function Wilcoxon signed-rank test p value

Baseline
90 100 100 65 60 66 65 52 (67.5100) (25100) (68.7100) (5075) (4480) (0100) (4575) (7087.5)

6 mo
85 (7097.5) 0.249 60 (0100) 0.008 100 (68.7100) 0.317 65 (4580) 0.076 72 (5684) <0.001 66 (33.3100) 0.098 65 (5080) 0.361 75 (5087.5) 0.005

12 mo
90 (65100) 0.691 60 (0100) 0.033 80 (60100) 0.007 70 (5080) 0.019 72 (5680) <0.001 100 (33.3100) 0.001 65 (5080) 0.021 75 (59.587.5) <0.001

Friedman test p value


0.095 0.007 <0.001 0.107 <0.001 <0.001 0.038 <0.001

In row for each scale, p value was determined by the Wilcoxon signed-rank test comparing the 6-mo scores and 12-mo scores to the baseline values. In rightmost column for each scale, p value was determined by the Friedman test comparing changes in the domain scores along the follow-up.

Comparing the baseline median values of each SF-36 single-scale score to those at 6 mo and 12 mo, there were statistically significant modifications in all of the domains except PF and GHP. Specifically, the 6-mo and 12-mo scores in the RP and BP domains were significantly lower than the baseline value ( p < 0.05). Conversely, the 6-mo and 12-mo scores in the EWB, RE, EF, and SF domains were significantly higher than those at baseline ( p < 0.05) (Table 3). Sensitivity analyses limited to specific subgroups of patients provided similar findings (Table 4).
3.1. 6-mo return to the baseline SF-36 score

The mean norm-based scores for each domain were within 1 SD of age- and sex-matched normative data for the Italian general population (data not shown extensively). At 6 mo after surgery, a percentage of patients ranging from 5981% across the different domains had scores overlapping the baseline values (Table 5). Some characteristics of patients and tumors turned out to be significantly associated with 6-mo recovery of baseline SF-36 scores. Specifically, educational level and NYHA class turned out to be predictive of return to baseline scores in the RE domain, body mass index (BMI) in the EWB domain, NYHA class in the RP domain, mode of presentation in the GHP domain, indication for NSS in the PF domain, and tumor histology in the BP domain. Finally, no variable was predictive of the 6-mo return to EF and SF baseline scores. Table 6 summarizes the prognostic factors predictive of the 6-mo return to the baseline scores in the different SF-36 domains.
3.2. 12-mo return to the baseline SF-36 score

Some characteristics of patients and tumors turned out to be significantly associated with 12-mo recovery of baseline SF-36 scores. Specifically, age was associated with return to the baseline score in the PF domain and NYHA class was associated with return to the baseline score in the PF domain and, in the univariate analysis only, to EWB scores. Moreover, occupational level was associated with the recovery of baseline scores in the RP domain and BMI in the BP domain. With regard to tumor characteristics, indication for NSS was associated with return to the baseline score in the SF domain. Moreover, clinical tumor size and pathologic tumor size were associated univariately with return to BP baseline score, while only pathologic size retained an independent predictive value in multivariate analysis once corrected for BMI. Similarly, tumor histology was an independent predictor of return to baseline score in the RE domain, once adjusted for NYHA class. Clinical tumor stage was significantly associated with return to baseline score in the GHP and EF domains. Table 7 summarizes the prognostic factors predictive of the 12-mo return to the baseline scores in the different SF36 domains. 4. Discussion

The mean norm-based scores for each domain were within 1 SD of age- and sex-matched normative data for the Italian general population (data not shown extensively). At 12 mo after surgery, across the different domains, 52 80% of the patients had 12-mo scores overlapping the baseline values (Table 5).

The data from our prospective study suggest that, although baseline scores were similar to those of the normative data from the age- and sex-matched Italian general population, significant modifications of the HRQoL as expressed by the SF-36 scores occurred during the first year after surgical treatment for renal neoplasm. Specifically, the scores in some domains concerning physical function (such as PF, RP, and BP) indicated a worsening of patients HRQoL, while an improvement was observed in the emotional and psychological aspects of the HRQoL as evaluated by increased scores in the EWB, RE, and SF domains. At 6 mo and 12 mo after surgery, 4981% of patients returned to the baseline HRQoL scores. Some characteristics of patients (age, BMI, educational level, occupational status, NYHA classification) and tumors (mode of presentation, stage, size, and

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Signicant increase ( p < 0.001) Signicant increase ( p = 0.022) Signicant increase ( p = 0.001) NS

Signicant increase ( p < 0.001) NS

Signicant increase ( p < 0.001) Signicant increase ( p = 0.022)

PF = physical function; RP = role limitations due to physical health problems; BP = bodily pain; GHP = general health perception; EWB = emotional well-being; RE = role limitations due to emotional problems; EF = energy/ fatigue; SF = social function.

Table 5 The percentage of patients reporting SF-36 scores which overlapped baseline values Domain 6 mo
PF RP BP GHP EWB RE EF SF 91 64 83 105 105 87 102 100 (70) (49) (64) (81) (81) (67) (79) (77)

SF

Cases (%) 12 mo
92 67 82 102 102 96 100 103 (71) (52) (64) (79) (79) (74) (78) (80)

Signicant increase ( p = 0.04) NS

Signicant increase ( p = 0.003)

EF

NS

NS

NS

NS

NS

Signicant increase ( p = 0.003) Signicant increase ( p = 0.005) Signicant increase ( p = 0.002) NS

Signicant increase ( p < 0.001) Signicant increase ( p = 0.041) Signicant increase ( p < 0.001) Signicant increase ( p = 0.003)

PF = physical function; RP = role limitations due to physical health problems; BP = bodily pain; GHP = general health perception; EWB = emotional well-being; RE = role limitations due to emotional problems; EF = energy/fatigue; SF = social function.

RE

histologic type) were significantly correlated with the return to baseline scores. Most of our results were original because no study with a similar design has been published. Specifically, a single prospective study evaluating HRQoL of patients with kidney tumors has been previously reported [13]; Onishi et al demonstrated that radiofrequency ablation had significantly lower impact on HRQoL than laparoscopic RN during the first week after surgery [13]. However, the study was small and evaluated only patients with small and clinically localized cancers. The other published retrospective studies of HRQoL were mainly focused on the impact of NSS and RN on HRQoL. Specifically, Poulakis et al evaluated 158 and 199 patients treated by NSS and RN, respectively, using SF-36 and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) [12]. The authors found that patients undergoing elective NSS had higher scores in the PF and RP domains, as well as lower scores for BP, compared with those undergoing imperative NSS or RN [12]. However, it is likely that these findings were related to the different baseline characteristics of the patients undergoing elective NSS, imperative NSS, and RN, but these data were not evaluable in a retrospective study. Conversely, Clark et al failed to show any significant impact of the type of operation on either the physical or the mental domains of the SF-36, while only self-reported remaining renal parenchyma was an independent predictor of HRQoL, anxiety about cancer recurrence, and the impact of cancer on overall health [10]. In our study, the baseline characteristics of the patients undergoing NSS and RN were overlapping in almost all of the SF-36 scales, while patients undergoing elective NSS had higher scores than those who underwent imperative partial nephrectomy only in the GHP domain (data not shown extensively). The 12-mo scores reproduced a very similar trend, with no significant difference observed in most of the SF-36 domains. However, patients undergoing elective NSS had significantly higher chances of returning to baseline PF scores 6 mo after surgery and significantly higher probability of returning to baseline SF scores 12 mo after surgery compared with those undergoing imperative NSS, regardless of the preoperative renal function. In contrast, the patients

Table 4 Subgroup analyses of SF-36 score variation in the different scales during the follow-up (Friedman test)

Signicant increase ( p = 0.005)

Signicant increase ( p = 0.039) NS

GHP

NS

NS

NS

NS NS

Signicant decrease ( p = 0.002) NS

Signicant decrease ( p < 0.001) NS

NS

NS

NS

NS

NS

Incidentally detected patients (n = 101) Symptomatic patients (n = 24) Clinically localized cancers (n = 114) Clinically locally advanced cancers (n = 15) Radical nephrectomy (n = 64) Elective nephron-sparing surgery (n = 65) Pathologically localized cancers (n = 91) Pathologically locally advanced cancers (n = 20)

Subgroup analysis

NS

NS

PF

Signicant decrease ( p = 0.002) NS

RP

NS

NS

Signicant decrease ( p = 0.001) Signicant decrease ( p = 0.001) NS

Signicant decrease ( p < 0.001) NS

Signicant decrease ( p = 0.001) NS

BP

NS

NS

Signicant increase ( p < 0.001) Signicant increase ( p < 0.001) Signicant increase ( p < 0.001) NS

Signicant increase ( p < 0.001) Signicant increase ( p = 0.024) Signicant increase ( p < 0.001) NS

EWB

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Table 6 Patients returning to baseline SF-36 scores 6 mo after surgery, stratified according to clinical and pathologic features Variable
Age, yr <65 (n = 66) !65 (n = 63) Gender Male (n = 81) Female (n = 48) BMI <25 (n = 49) !25 (n = 78) Years of education 8 (n = 73) >8 (n = 56) Occupation Full-time employed (n = 67) Not employed (n = 62) ECOG PS 0 (n = 117) !1 (n = 12) Charlson score 0 (n = 85) !1 (n = 44) NYHA class 1 (n = 115) !2 (n = 14) Mode of presentation Incidental (n = 105) Symptomatic (n = 24) Clinical tumor size 4 cm (n = 70) >4 cm (n = 59) Clinical N stage (TNM, 2002) cN0 (n = 127) cN1 (n = 2) Clinical M stage (TNM, 2002) cM0 (n = 121) cM1 (n = 8) Kind of surgery Radical nephrectomy (n = 64) Partial nephrectomy (n = 65) Indication for partial nephrectomy Elective (n = 57) Imperative (n = 8) Pathological tumor size 4 cm (n = 74) >4 cm (n = 55) Histological type Benign tumors (n = 20) RCC (n = 109) Pathological T stage (TNM, 2002) pT2 (n = 89) ! pT3 (n = 20) Pathological N/M stage (TNM, 2002) pN0M0 (n = 121) pN1 or M1 (n = 8)

PF, %

RP, %

BP, %

GHP, %

EWB, %

RE, %

EF, %

SF, %

76 65

52 48

65 64

83 79

80 83

74 60

80 78

85 70

74 65

48 52

69 56

80 83

82 81

68 67

79 79

77 79

67 72

49 50

63 64

76 85

69* 89

65 68

71 83

76 78

66 77

44 57

64 64

78 86

80 84

55* 84

75 84

77 78

72 69

48 52

61 68

78 86

82 81

66 69

73 86

72 84

71 67

52 25

64 83

80 100

82 75

68 58

78 92

76 92

73 66

53 39

61 71

81 82

80 84

73 57

77 82

79 75

74 57

53* 21

64 64

80 93

83 71

72* 29

79 79

77 78

71 67

49 54

65 63

87* 58

83 75

70 58

80 75

80 67

74 66

46 54

61 68

84 78

83 80

70 64

79 80

81 73

70 100

48 100

64 50

81 100

81 100

66 100

78 100

77 100

71 62

50 50

64 62

87 81

82 75

69 50

79 75

78 62

64 77

53 46

70 59

81 82

80 83

66 69

81 77

81 74

84* 25

49 25

60 50

81 88

83 88

72 50

79 63

75 63

73 67

46 55

61 69

82 80

81 82

66 69

77 82

78 76

70 71

48 60

40 69

82 80

90 80

80 65

75 80

90 75

72 65

47 50

66* 80

82 80

81 75

67 55

78 90

79 60

71 62

50 50

64 62

87 81

82 75

69 50

79 75

78 62

PF = physical function; RP = role limitations due to physical health problems; BP = bodily pain; GHP = general health perception; EWB = emotional well-being; RE = role limitations due to emotional problems; EF = energy/fatigue; SF = social function; ECOG PS = Eastern Cooperative Oncology Group performance status; NYHA = New York Heart Association; RCC = renal cell carcinoma. * Signicant in univariate analysis.

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Table 7 Patients returning to baseline SF-36 scores 12 mo after surgery stratified according to clinical and pathologic features
Variable
Age, yr <65 (n = 66) !65 (n = 63) Gender Male (n = 81) Female (n = 48) BMI <25 (n = 49) !25 (n = 78) Years of education 8 (n = 73) >8 (n = 56) Occupation Full-time employed (n = 67) Not employed (n = 62) ECOG PS 0 (n = 117) !1 (n = 12) Charlson score 0 (n = 85) !1 (n = 44) NYHA class 1 (n = 115) !2 (n = 14) Mode of presentation Incidental (n = 105) Symptomatic (n = 24) Clinical tumor size 4 cm (n = 70) >4 cm (n = 59) Clinical N stage (TNM, 2002) cN0 (n = 127) cN1 (n = 2) Clinical M stage (TNM, 2002) cM0 (n = 121) cM1 (n = 8) Surgical approach Open surgery (n = 116) Laparoscopic surgery (n = 13) Kind of surgery Radical nephrectomy (n = 64) Partial nephrectomy (n = 65) Indication for partial nephrectomy Elective (n = 57) Imperative (n = 8) Pathological tumor size 4 cm (n = 74) >4 cm (n = 55) Histological type Benign tumors (n = 20) RCC (n = 109) Pathological T stage (TNM, 2002) pT2 (n = 89) ! pT3 (n = 20) Pathological N/M stage (TNM, 2002) pN0M0 (n = 121) pN1 or M1 (n = 8)

PF, %

RP, %

BP, %

GHP, %

EWB, %

RE, %

EF, %

SF, %

83* 59

54 49

67 60

80 78

79 79

80 68

79 76

83 76

74 67

49 56

64 62

80 77

76 83

74 75

78 77

75 87

73 69

57 47

75* 55

82 77

73 82

80 70

80 76

84 77

74 68

49 55

66 61

81 77

80 79

68 82

78 77

82 77

79 63

63* 40

72 55

77 81

75 84

79 69

79 76

85 74

73 50

53 42

63 68

79 83

80 67

76 58

79 67

80 83

75 64

58 41

64 64

75 86

79 79

78 68

75 82

81 77

74* 50

54 36

65 50

78 86

79 79

77* 50

78 72

80 79

70 79

51 58

60 79

79 79

78 83

74 75

77 79

80 79

70 73

47 58

56* 73

83 74

84 73

77 71

80 75

79 81

71 100

51 100

63 100

79 100

79 50

74 100

77 100

80 50

71 75

51 62

64 62

78 87

79 75

74 75

77 87

80 75

70 85

51 61

62 77

78 92

78 84

74 77

78 77

78 92

64 78

47 57

70 57

81 77

80 78

73 75

75 80

83 77

82 50

61 25

60 37

75 87

79 75

75 75

81 75

82* 37

70 73

47 58

54* 76

77 82

77 82

72 78

77 78

77 84

75 71

60 50

70 62

75 80

77 90

95* 71

75 78

77 95

70 75

52 45

60 75

79 85

81 60

72 65

77 80

80 60

71 75

51 62

64 62

78 87

79 75

74 75

77 87

80 75

PF = physical function; RP = role limitations due to physical health problems; BP = bodily pain; GHP = general health perception; EWB = emotional well-being; RE = role limitations due to emotional problems; EF = energy/fatigue; SF = social function; ECOG PS = Eastern Cooperative Oncology Group performance status; NYHA = New York Heart Association; RCC = renal cell carcinoma. * Signicant in univariate analysis. # Signicant in multivariate analysis.

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with pathologic tumors sized <4 cmwho, in our center, are the most likely to have undergone elective NSS through flank incisionhad lower scores in the BP domain 12 mo after surgery and less chance of returning to the baseline scores compared with those patients with larger tumors. These figures indicate that the long-term morbidity of flank incision might be significantly higher than that for transperitoneal anterior RN. Most of those patients might be better served by a pure laparoscopic or a robot-assisted NSS. These procedures, however, are routinely performed only in a few institutions because such procedures are still considered among the most demanding laparoscopic ones, and the open approach is usually selected in many centers. As expected using a generic questionnaire, several clinical characteristics of the patients (ie, age, BMI, educational level, occupational status, and NYHA class) turned out to be significantly associated with the return to baseline HRQoL. More interestingly, some other clinical and pathologic features of kidney cancer turned out to be significantly associated with the return of HRQoL. Specifically, mode of presentation was found to be significantly associated with the 6-mo return to the baseline scores in the GHP domain, and symptomatic patients experienced the least improvement. More importantly, histologic type was an independent predictor of RE scores; patients harboring benign tumors had significantly better scores. The data clearly suggest that the emotional impact of the diagnosis of cancer can significantly affect the HRQoL of patients even 12 mo after surgery, indicating that some patients might benefit from some kind of psychological intervention. However, further clinical studies are needed to accurately identify those patients and the most appropriate intervention. The results of our study can be useful for several reasons. First, they might be useful in counseling patients before surgery in order to explain appropriately the probability and time of returning to the preoperative HRQoL. Moreover, about 2050% of the patients did not regain the baseline HRQoL score within the first year following surgery, and this study indicated that clinical variables of patients and tumors played a major role, suggesting that some specific measure should be studied in those patients with unfavorable prognostic factors. Second, our data provide a reference standard for evaluating the relative impacts on HRQoL of other minimally invasive competing treatments for renal tumors. Thirdly, our data suggest that patients with small cancers undergoing elective partial nephrectomy through a flank incision had a significant impairment in the BP score even 12 mo after surgery, which might be an issue in favor of a minimally invasive approach. The study had several shortcomings. Although the response rate was quite high (85%), the clinical, pathologic, and follow-up characteristics of the patients who did not respond to questionnaire were significantly worse than those of the patients filling out the follow-up questionnaire, with a significantly lower incidence of disease progression and number of cancer-related deaths observed in the patients whose questionnaires were evaluated. To our knowledge, the present study is the first to report the characteristics of the patients not responding to the

questionnaire, which highlights the role of a prospective evaluation. Quality of life of patients with disease progression is clearly affected by the natural history of cancer, and these patients usually have a short median survival, which made the study timetable inappropriate for their optimal evaluation. Alternatively, the major merit of the present study is to provide HRQoL data on those patients with good and intermediate prognosis, who are the large majority of those undergoing surgical treatment. An important shortcoming of the present study could be represented by the lack of a disease-specific questionnaire. A questionnaire specific for kidney cancer, the Functional Assessment of Cancer TherapyKidney Symptom Index (FKSI-15), has recently been developed [27], and several translations are currently available. However, the FKSI-15 was developed in patients with advanced or recurrent kidney cancer, which would have made its use inappropriate for our setting. Moreover, the use of other questionnaires focused on specific aspects of quality of life such as, for example, anxiety or social relations might have been of interest. Considering the long life expectancy of most patients with kidney cancers, the 12-mo follow-up might be insufficient to evaluate the long-term impact of both disease and treatments on HRQoL. Our study protocol, however, included a 24-mo evaluation of the HRQoL, but the collection of the 24-mo data is ongoing and will be the subject of future reports. Finally, the study cohort was not very large, which might have affected some of the statistical comparisons, and only a small percentage of our patients was treated laparoscopically, which did not allow any comparison between different surgical approaches.

5.

Conclusions

Although baseline scores were similar to normative data from the age- and sex-matched Italian general population, we observed significant modifications of the HRQoL as expressed by the SF-36 scores during the first year after surgical treatment for renal neoplasm. At 6 mo and 12 mo after surgery, 1951% of patients did not achieve scores comparable to the baseline values. Mode of presentation, stage of the primary tumor, tumor size, histologic tumor type, and some of the clinical features of the patients (eg, age, BMI, education, occupation, and NYHA class) can significantly affect the recovery of the baseline HRQoL scores 6 mo and 12 mo after surgery.

Author contributions: Vincenzo Ficarra had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Ficarra, Novara. Acquisition of data: Secco, Botteri, De Marco. Analysis and interpretation of data: Novara. Drafting of the manuscript: Novara. Critical revision of the manuscript for important intellectual content: Novara, Artibani, Ficarra. Statistical analysis: Novara.

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Obtaining funding: None. Administrative, technical, or material support: Artibani, Ficarra. Supervision: Artibani, Ficarra. Other (specify): None. Financial disclosures: I certify that all conicts of interest, including specic nancial interests and relationships and afliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/afliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents led, received, or pending), are the following: None. Funding/Support and role of the sponsor: None.

for localized renal cell carcinoma: impact of the amount of remaining renal tissue. Urology 2001;57:2526. [11] Ficarra V, Novella G, Sarti A, et al. Psycho-social well-being and general health status after surgical treatment for localized renal cell carcinoma. Int Urol Nephrol 20022003;34:4416. [12] Poulakis V, Witzsch U, de Vries R, Moeckel M, Becht E. Quality of life after surgery for localized renal cell carcinoma: comparison between radical nephrectomy and nephron-sparing surgery. Urology 2003; 62:81420. [13] Onishi T, Nishikawa K, Hasegawa Y, et al. Assessment of healthrelated quality of life after radiofrequency ablation or laparoscopic surgery for small renal cell carcinoma: a prospective study with medical outcomes Study 36-Item Health Survey (SF-36). Jpn J Clin Oncol 2007;37:7504. [14] Ljungberg B, Hanbury DC, Kuczyk MA, et al. Renal cell carcinoma guideline. Eur Urol 2007;51:150210.

References
[1] Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin 2008;58:7196. [2] Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 2007;18:58192. [3] Kane CJ, Mallin K, Ritchey J, Cooperberg MR, Carroll PR. Renal cell cancer stage migration: analysis of the National Cancer Data Base. Cancer 2008;113:7883. [4] The World Health Organization Quality of Life assessment (WHOQOL): position paper from the World Health Organization. Soc Sci Med 1995; 41:14039. [5] Khanna D, Tsevat J. Health-related quality of life-an introduction. Am J Manag Care 2007;13(Suppl 9):S21823. [6] McCabe C, Begley C, Collier S, McCann S. Methodological issues related to assessing and measuring quality of life in patients with cancer: implications for patient care. Eur J Cancer Care (Engl) 2008;17:5664. [7] Litwin MS, Fine JT, Dorey F, et al. Health related quality of life outcomes in patients treated for metastatic kidney cancer: a pilot study. J Urol 1997;157:160812. [8] Pannek J, Hallner D, Kugler J, et al. Quality of life of patients with renal cell carcinoma or prostate cancer after radical surgery. Inter Urol Nephrol 1997;29:63743. [9] Shinohara N, Harabayashi T, Sato S, Hioka T, Tsuchiya K, Koyanagi T. Impact of nephron-sparing surgery on quality of life in patients with localized renal cell carcinoma. Eur Urol 2001;39:1149. [10] Clark PE, Schover LR, Uzzo RG, Hafez KS, Rybicki LA, Novick AC. Quality of life and psychological adaptation after surgical treatment

[15] Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:64955. [16] Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol 1994;47:124551. [17] Dripps RD, Lamont A, Eckenhoff JE. The role of anesthesia in surgical mortality. JAMA 1961;178:2616. [18] Criteria Committee for the New York Heart Association. Nomenclature and Criteria for Disease. 6th ed. Boston, MA: Little Brown and Company; 1964. [19] Patard JJ, Cindolo L, Ficarra V, et al. Multi-institutional validation of a symptom based classication for renal cell carcinoma. J Urol 2004;172:85862. [20] Kovacs G, Akhtar M, Beckwith BJ, et al. The Heidelberg classication of renal cell tumors. J Pathol 1997;183:1313. [21] Greene FL, Page D, Morrow M, et al. editors. AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer; 2002. [22] Fuhrman SA, Lasky LC, Limas C. Prognostic signicance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol 1982;6:65563. [23] Hays RD, Sherbourne CD, Mazel RM. The RAND 36-Item Health Survey 1.0. Health Econ 1993;2:21727. [24] Apolone G, Mosconi P, Wore JE. Questionario sullo stato di salute SF-36. Milan, Italy: Guerini e Associati Editori; 1997. [25] Litwin MS, Melmed GY, Nakazon T. Life after radical prostatectomy: a longitudinal study. J Urol 2001;166:58792. [26] Guyatt GH, Bombardier C, Tugwell PX. Measuring disease-specic quality of life in clinical trials. CMAJ 1986;134:88995. [27] Cella D, Yount S, Du H, et al. Development and validation of the Functional Assessment of Cancer TherapyKidney Symptom Index (FKSI). J Support Oncol 2006;4:1919.

Editorial Comment on: Factors Predicting HealthRelated Quality of Life Recovery in Patients Undergoing Surgical Treatment for Renal Tumors: Prospective Evaluation Using the RAND SF-36 Health Survey Carlo Terrone ` Division of Urology, Maggiore della Carita Hospital, University of Eastern Piedmont, Corso Mazzini, 18, 28100, Novara, Italy carlo.terrone@med.unipmn.it The issue of quality of life is becoming crucial in oncology. Health-related quality of life (HRQoL) is used to

evaluate the outcome of a treatment and is even used as a main criterion to choose among different interventions with similar efficacy and morbidity. Several questionnaires have been used to evaluate HRQoL in patients with renal tumors, but they are not specific for this disease. The Functional Assessment of Cancer TherapyKidney Symptom Index and the RCC Symptom Index are currently undergoing comparative content validation [1,2]. Furthermore, defining a minimal, clinically meaningful improvement or impairment during validation is critical to provide practicing physicians, medical directors, and health policy makers with a useful HRQoL tool.

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Few studies have addressed the topic of HRQoL in renal tumors, and most of them have significant biases: retrospective design, small series, high percentage of patients who did not respond to the questionnaires, absence of baseline data [3,4]. Controversial results can also be explained by the use of different questionnaires. In this issue of European Urology, Novara et al used a well-designed study to prospectively evaluate HRQoL of 129 consecutive patients who underwent nephron-sparing surgery (NSS) or radical nephrectomy (RN) for a kidney tumor [5]. The patients completed the HRQoL questionnaire SF-36 before surgery and at 6 mo, 12 mo, and 24 mo afterward. No significant differences were found among the baseline scores and normative data for the national general population. After surgery, a statistically significant impairment in the physical domains and improvement in the emotional domains were observed. Most patients returned to baseline scores after surgery. Age, body mass index, educational level, occupational status, New York Heart Association functional class, tumor mode of presentation, pathologic stage, size, and histologic subtype were associated with return to the baseline HRQoL scores. Patients undergoing elective NSS had better results compared with those undergoing imperative NSS. Alternatively, patients with small cancers undergoing elective NSS through a flank incision had a significant impairment in the bodily pain score, even 12 mo after surgery. Unfortunately, in this series only a few patients underwent a laparoscopic treatment; therefore, the influence of this approach on HRQoL could not be assessed. One could expect a benefit from laparoscopic RN and NSS compared with open procedures. In recent years, other minimally invasive approaches for the treatment of renal tumors have gained popularity. Further studies are

required to compare HRQoL outcomes of these techniques with those of standard treatments. It could be also interesting to investigate the influence on postoperative HRQoL of other variables such as the quality of counseling provided by physicians and the frequency of follow-up exams and visits.

References
[1] Cella D, Yount S, Du H, et al. Development and validation of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI). J Support Oncol 2006;4:1919. [2] Harding G, Cella D, Robinson Jr D, et al. Symptom burden among patients with renal cell carcinoma (RCC): content for a symptom index. Health Qual Life Outcomes 2007;5:3446. [3] Lesage K, Joniau S, Fransis K, et al. Comparison between open partial and radical nephrectomy for renal tumours: perioperative outcome and health-related quality of life. Eur Urol 2007;51:614 20. [4] Dillenburg W, Poulakis V, Skriapas K, et al. Retroperitoneoscopic versus open surgical radical nephrectomy for large renal cell carcinoma in clinical stage cT2 or cT3a: quality of life, pain and reconvalescence. Eur Urol 2006;49:31422. [5] Novara G, Secco S, Botteri M, De Marco V, Artibani W, Ficarra V. Factors predicting health-related quality of life recovery in patients undergoing surgical treatment for renal tumors: prospective evaluation using the RAND SF-36 health survey. Eur Urol 2010;57:11222.

DOI: 10.1016/j.eururo.2009.04.024 DOI of original article: 10.1016/j.eururo.2009.04.023

Editorial Comment on: Factors Predicting HealthRelated Quality of Life Recovery in Patients Undergoing Surgical Treatment for Renal Tumors: Prospective Evaluation Using the RAND SF-36 Health Survey Richard Zigeuner Department of Urology, Medical University Graz, Auenbruggerplatz 7, A-8036 Graz, Austria richard.zigeuner@medunigraz.at This study is important because, for the first time, the impact of kidney cancer surgery on health-related quality of life (QoL) has been evaluated prospectively compared with the baseline situation prior to treatment and with the general population [1]. An increasing number of renal masses are being diagnosed incidentally. These tumours are associated with favourable outcomes; thus, QoL is an important factor for the affected patients. At 1 yr after surgery, the majority, yet not all, of patients had returned to baseline values. Impairment was mainly noted in physical functions, whereas an improvement was noted in emotional and psychological domains.

Until recently, surgery used to be the only option for patients with solid renal tumours. Alternative treatments including radiofrequency ablation, cryotherapy, or highintensity focused ultrasound are being increasingly utilised in small incidental renal masses [24]. Moreover, even observation of renal masses is becoming an accepted alternative to immediate interventions [5]. Although no reliable long-term outcome data are available for these treatments yet, the minimally invasive aspects might be attractive for the affected patients. With regard to oncologic outcomes, it cannot be expected that ablative techniques will ever be superior to surgery, which still has to be considered standard of care. On this background, QoL issues might affect treatment decisions. Presently, comparable well-conducted studies evaluating QoL in patients undergoing ablative techniques or surveillance are lacking and are needed. Only if the minimally invasive techniques will show relevant superiorities over surgery with respect to QoL issues and only if these hypothetical advantages will be well balanced with oncologic outcomes will application

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of these novel methods be justified in future. With the present study, baseline data are available, to which other methods must be compared.

[3] Klingler HC, Susani M, Seip R, Mauermann J, Sanghvi N, Marberger MJ. A novel approach to energy ablative therapy of small renal tumours: laparoscopic high-intensity focused ultrasound. Eur Urol 2008;53:8108. [4] Goel RK, Kaouk JH. Probe ablative treatment for small renal masses: cryoablation vs. radio frequency ablation. Curr Opin Urol

References
[1] Novara G, Secco S, Botteri M, De Marco V, Artibani W, Ficarra V. Factors predicting health-related quality of life recovery in patients undergoing surgical treatment for renal tumors: prospective evaluation using the RAND SF-36 health survey. Eur Urol 2010;57:11222. [2] Mouraviev V, Joniau S, Van Poppel H, Polascik TJ. Current status of minimally invasive ablative techniques in the treatment of small renal tumours. Eur Urol 2007;51:32836.

2008;18:46773. [5] Kunkle DA, Egleston BL, Uzzo RG. Excise, ablate or observe: the small renal mass dilemmaa meta-analysis and review. J Urol 2008;179:122733.

DOI: 10.1016/j.eururo.2009.04.025 DOI of original article: 10.1016/j.eururo.2009.04.023