Qual Life Res DOI 10.1007/s11136-014-0729-1

Effect of perioperative complications and functional outcomes on health-related quality of life after radical prostatectomy Bjo¨rn Lo¨ppenberg • Christian von Bodman Marko Brock • Florian Roghmann • Joachim Noldus • Rein Ju¨ri Palisaar

•

Accepted: 27 May 2014 Ó Springer International Publishing Switzerland 2014

Abstract Purpose Radical prostatectomy is a commonly performed procedure with perioperative complication rates of 30 % using standardized reporting methodology. We aim to determine whether perioperative complications and functional outcomes impact quality of life 1 year after surgical treatment. Patients and methods Quality of life, functional and oncological outcomes were assessed in patients who underwent open retropubic radical prostatectomy at a single academic institution between 2003 and 2009, preoperatively and 1 year after surgery using the EORTC QLQC30, the IIEF-5 and an institutional questionnaire. Perioperative complications were recorded using the Clavien– Dindo classification. Patients without complications were compared to patients with any, low- or high-grade complications. The global health score domain of the EORTC QLQ-C30 is reported for various oncological and functional outcomes and contrasted to stratified categories of complications and functional outcomes. Results A full dataset was available for 29.5 % (n = 856) of all patients. The overall complication rate was 27.5 % (235/856). A total of 307 complications were recorded of whom 88.9 % (273/307) were low grade. In this study, population global health perception did not decline after surgery (70.5 ± 21.2 vs. 74.4 ± 19.7; p \ 0.0001). Complications showed only statistical but no clinical meaningful influence on global health perception as well as on

B. Lo¨ppenberg (&)
C. von Bodman
M. Brock
F. Roghmann
J. Noldus
R. J. Palisaar Department of Urology and Neuro-Urology, Marien Hospital Herne, Ruhr-University Bochum, Widumerstrasse 8, 44627 Herne, Germany e-mail: [email protected]

functional and symptom scales. Patients who met combined outcome criteria experienced the best postoperative global health score (86.0 ± 13.1 and 86.0 ± 14.2). Conclusions Perioperative complications and functional outcomes have a measurable impact on quality of life 1 year following surgery. While perioperative complications have a statistical effect, functional outcomes showed a clinically more profound effect on postoperative global health perception. Keywords Complications
Prostatectomy
Prostate neoplasm
Quality of life

Introduction The aim of prostate cancer surgery is cure from cancer and if possible, preservation of continence and potency, the latter combination known as ‘‘Trifecta’’ [1]. Patel et al. [2] extended this condition by two further aims: negative surgical margins and the absence of complications calling it ‘‘Pentafecta.’’ Few studies addressed the impact of perioperative complications on quality of life: Treiyer et al. [3] recently assessed predictors impacting quality of life after radical prostatectomy. The absence of postoperative complications was identified as an independent predictor of return to baseline physical and mental health. Similarly, Perl et al. [4] demonstrated that patients with perioperative complications showed an increased likelihood for a lower postoperative quality of life. In patients who underwent surgery for esophageal and cardia cancer [5], cardiac complications and infections adversely impacted quality of life in this study. Unfortunately, no standardized tools to assess and report complications were applied in the aforementioned series.

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Qual Life Res Table 1 Clavien–Dindo classification of complications [6] Grade I

Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic and radiological interventions. Allowed therapeutic regimens are as follows: drugs as antiemetics, antipyretics, analgetics, diuretics, electrolytes and physiotherapy. This grade also includes wound infections opened at the bedside

Grade II

Requiring pharmacological treatment with drugs other than such allowed for grade I complications Requiring surgical, endoscopic or radiological intervention

Grade III a

Intervention not under general anesthesia

b

Intervention under general anesthesia

Grade IV

a b Grade V

Life-threatening complication (including central nervous complications) requiring intensive care unit management Single organ dysfunction (including dialysis) Multiorgan dysfunction Death of a patient If the patient suffers from a complication at the time of discharge, the suffix ‘‘d’’ is added to the respective grade of complication. This label indicates the need for a follow-up to fully evaluate the complication

Today, the Clavien and Dindo [6] reporting system (CDC) (Table 1) is widely accepted in the scientific literature to report complications in a standardized manner. The reported complication rates using the CDC for robotassisted [7], laparoscopic [8] and open retropubic radical prostatectomy [9] are 21.6, 33.1 and 27.5 %, respectively. However, it is not known whether perioperative complications assessed by a standardized reporting methodology might impact quality of life after surgical treatment. We aim to determine the impact of standardized CDC assessed complications and functional outcomes on healthrelated quality of life (HRQOL) 1 year after open retropubic radical prostatectomy.

Patients and methods Between August 2003 and August 2009, 2,899 consecutive patients underwent open retropubic radical prostatectomy for prostate cancer as described by Walsh [10] with minor modifications [11] at a single academic institution. All patients signed informed consent to participate in this study, and internal review board approval was obtained. Complications Complication and outcome data for 2,899 patients were prospectively collected and recorded. All complications were retrospectively classified according to the CDC [6]

123

scale (grades I–V) by an impartial urologist who was not involved in the care of the patient. All medical and surgical complications which occurred during the hospital stay were included. In case of multiple complications, only the highest grade per patient was considered for statistical analysis. Complications were categorized as overall (CDC I–V), low-grade (CDC I–II) and high-grade complications (CDC III–V). Functional results Postoperative functional results, disease status and HRQOL were assessed 12 months following surgical treatment. Continence status (continence defined as ‘‘no pad use,’’ incontinence defined as ‘‘utilization of 1 pad/24 h,’’ and severe incontinence defined as ‘‘utilization of C2 pads/ 24 h’’) was assessed using an unvalidated institutional questionnaire (Appendix). Preoperative continence status was not assessed. Pre- and postoperative potency status was assessed using the IIEF-5 questionnaire [12]. Sufficient erectile function was defined as an IIEF-5 score of C17 points with or without usage of phosphodiesterase type 5 inhibitors. Freedom of disease was defined as negative margin, Nx or N0, PSA B 0.2 ng/ml postoperative and no adjuvant postoperative therapy. Frequencies of patients achieving ‘‘Trifecta’’ or ‘‘Pentafecta’’ status were calculated. For determination of the latter parameters, patients with preexisting erectile dysfunction, those who did not undergo a nerve-sparing procedure or with insufficient information to determine postoperative erectile function and disease status, were considered to have failed achievement of ‘‘Trifecta’’ or ‘‘Pentafecta’’ status. Quality of life HRQOL was assessed by the German version of the EORTC QLQ-C30 questionnaire [13] pre- and 1 year postoperatively. The validated questionnaire assesses global health perception as well as several functional and symptom scales. A high score in the global health status (GHS), functional scales and symptom scales indicates high global health perception, satisfactory functional outcomes, as well as high symptom intensity, respectively. Scores range from 0 to 100. Differences of EORTC QLQ-C30 scores between groups were interpreted as described by Osoba et al. [14] and Cocks et al. [15]. At admission, 1 day prior to surgery, all questionnaires were handed out and explained to the patient in detail by the attending physician. Patients were asked to complete the questionnaires voluntarily and on their own without the presence of a physician. The return of filled out

Qual Life Res

questionnaires was no prerequisite condition for further treatment. A set of all questionnaires accompanied by a prepaid return envelope was sent to all patients 1 year postoperatively. Returned questionnaires were entered into a database by an independent data manager. The scores for GHS, functional scales and symptom scales were calculated according to the EORTC [16] instructions. Only patients who returned the pre- and postoperative quality of life questionnaires were included for statistical analysis. Statistics Mean and standard deviation as well as median and IQR are reported for continuous parametric and nonparametric variables as appropriate. The Mann–Whitney U test [17] was used to compare means in continuous nonparametric variables. The Wilcoxon rank test [18] was used to compare QLQ-C30 domains pre- and postoperatively. Groups were compared using the v2-test [19]. The same tests were applied to compare the study population with those patients, who had missing pre- or postoperative questionnaires, and we controlled for differences in demographic, clinical and histopathological parameters as well as for differences in the incidence of any, low- or high-grade complications. For determining the influence of complications on HRQOL, the GHS and all functional and symptom -scales of the EORTC QLQ-C30 were calculated. For determining the impact of continence, potency, biochemical recurrence, ‘‘Trifecta’’ and ‘‘Pentafecta,’’ on postoperative quality of life, only the GHS was determined. To address for potentially confounding variables such as body mass index (BMI), American society of anesthesiologists score (ASA), clinical stage and variables which were significantly associated (p \ 0.05) with presence of complications and follow-up GHS in a previous analysis [20], we included these variables in an analysis of covariance (ANCOVA) multivariate model to determine whether postoperative complications and functional outcomes are associated with GHS after controlling for these variables. Clinical stage and ASA were categorized in cT1, cT2, cT3, ASA B2 and ASA C3, respectively. The preoperative GHS was included in the model to control for baseline quality of life. Interaction between complications and baseline GHS was assessed by including an interaction term between these two variables in the multivariate ANCOVA model. If complication status was statistically associated with follow-up GHS, a secondary ANCOVA was conducted to determine whether a difference exists between no complications, low-grade complications, and high-grade complications and potential confounders. A two-sided p \ 0.05 was considered statistically significant. Statistical analyses were performed with the SPSS StatisticsÒ21 (IBM) commercial software package.

Results Our final study population consists of n = 856 men, who returned pre- and postoperative EORTC QLQ-C30 questionnaires. The return rate of the preoperative questionnaire was 40.4 % (1,171/2,899), and the postoperative questionnaire return rate 12 months after surgical treatment was 80.2 % (2,042/2,899). In 17.4 % (507/2,899), no questionnaires were returned at all. The demographic, clinical, histopathological parameters and functional outcomes of the final study population of n = 856 patients are shown in Table 2. A comparison of the patients with missing pre- or postoperative quality of life data with the study population did not show any significant differences in regard to clinical and pathological variables (Table 2). There were no statistical significant differences between GHS scores concerning patients who only answered the preoperative questionnaire (n = 315) compared to all others who answered the preoperative questionnaire (n = 856) (p = 0.900; GHS 70.28 ± 21.54 vs. 70.5 ± 21.20) and no differences for those who only answered the postoperative questionnaire (n = 1,186) compared to all other patients (n = 856) who answered the postoperative questionnaire (p = 0.391; GHS 73.5 ± 19.9 vs. 74.4 ± 19.7) (Table 6). Mean hospital stay duration was 11.27 ± 2.7 days (range 7–30). Complications We found an overall complication rate of 27.5 % (235/856) with a total of 307 complications in 235 patients. Of the entire study cohort, 21 % (180/856) had a single complication and 6.4 % (57/856) had two or more complications. The majority of complications were managed conservatively. We observed 62.8 % (193/307) grade I complications in 20.8 % (178/856) of patients and 26.1 % (80/307) grade II complications in 8.6 % (74/856) of men. 10.4 % (32/307) grade III complications were observed in 3.6 % (31/856) of men including 6.2 % (19/307) grade IIIA and 4.2 % (13/307) grade IIIB complications. We observed 0.7 % (2/307) grade IV complications in 0.2 % (2/856) of men, of whom both experienced a grade IVA complication. Of all patients, 25.8 % (221/856) had a low-grade complication (grades I and II), 3.7 % (32/856) a high-grade complication (grades III–V) and 2.1 % (18/856) had concomitant, low- and high-grade complications. The most frequent complication was prolonged catheterization ([14 days) recorded in 14.6 % (125/856) of cases. The main reason for surgical reintervention was a symptomatic lymphocele, which occurred in 1.6 % (14/856) of all men. Table 3 gives an overview of medical and surgical complications and consecutive interventions in the study population of 856 patients. Of all 2,899 patients, the 90 day

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Qual Life Res Table 2 Demographic, clinical and functional parameters of study population (n = 856) and comparison of clinical and histopathological parameters to patients with incomplete quality of life data (n = 2042) Study population Mean ± SD; n (%) Age

63.42 ± 6.6

Table 2 continued Study population Mean ± SD; n (%)

Incomplete data Mean ± SD; n (%) 63.86 ± 6.3

p   

0.199

  

Body mass index Prostate volume

29.96 ± 3.3 36.27 ± 17.3

27.21 ± 3.4 36.47 ± 18.2

0.084 0.977  

PSA (ng/ml)

9.86 ± 9.8

9.93 ± 11.04

0.845  

74 (8.6)

147 (7.8) àà

0.381

170 (19.9)

C2

97 (11.3)

No evidence of diseasea

Mean ± SD; n (%)

p

587 (68.6)

Proportion of patients achievingb

ASA score group 1

1

Incomplete data

Trifecta

71 (8.2)

Pentafecta

49 (5.7)

PSA prostate-specific antigen, ASA American society of anesthesiologists, IIEF International Index of erectile function

2

553 (69.6)

1,318 (69.9)

3

168 (21.1)

418 (22.1)

a Defined as negative margin, Nx or N0, PSA B0.1, no adjuvant postoperative therapy

Missing

61 (7.1)

159 (7.8)

b

399 (46.6)

943 (46.2)

Only for patients without preoperative erectile dysfunction and unior bilateral nerve-sparing

Clinical stage cT1 cT2

378 (44.1)

888 (43.5)

cT3

79 (9.3)

211 (10.3)

544 (63.5)

1,331 (65.2)

  

Mann–Whitney U test

àà

àà

Chi square test

àà

0.808

Biopsy Gleason grade 235 (27.4)

527 (25.8)

77 (9.1)

184 (9.0)

mortality rate was 0.2 % (5/2,899). The patients deceased due to septic complications (n = 2), myocardial infarction (n = 2) and pulmonary embolism (n = 1).

pT0

1 (0.1)

3 (0.1)

Functional results

pT2

605 (70.7)

1,483 (72.7)

pT3

243 (28.4)

543 (26.6)

pT4

7 (0.8)

13 (0.6)

R0

735 (85.9)

1,781 (87.2)

R1

121 (14.1)

261 (12.8)

Nx

190 (22.1)

507 (24.8)

N0

636 (74.3)

1,468 (71.9)

N1

30 (3.6)

67 (3.3)

B6 7 C8 Pathological stage

0.475

0.722àà

Margin status 0.364àà

Nodal status 0.326àà

Specimen Gleason grade B6

407 (47.5)

926 (45.3)

7 C8

312 (36.4) 137 (16.0)

784 (38.4) 332 (16.3)

IIEF-5 C 17 Preoperative

446 (52.1)

Postoperative

121 (14.1)

IIEF-5 \ 17 Preoperative

267 (31.2)

Postoperative

690 (80.6)

Missing

Quality of life

Preoperative

143 (16.7)

Postoperative

45 (5.3)

Pad usage/24 h No pad

123

0.245àà

The overall postoperative continence rate was 68.6 % (589/ 856). One and two or more pads per day were used by 19.9 % (170/856) and 11.3 % (97/856), respectively. In 23.4 % (200/856) and 38.1 % (326/856), a uni- or bilateral nerve-sparing was performed. Preoperatively, 31.2 % (267/856) had an erectile dysfunction. Postoperatively, 36.2 % (121/334) of preoperatively potent patients, who were treated with a nerve-sparing procedure, had sufficient erections for intercourse. In 5.3 % (45/856) of the study population, no information of postoperative erectile function was provided. In 68.6 % (589/856) of the cases, no evidence of recurrence or persistent disease was observed. Insufficient information on postoperative prostate-specific antigen or adjuvant therapies made determination of disease status impossible in 11.6 % (99/856) of the cases. The ‘‘Trifecta’’ or ‘‘Pentafecta’’ criteria were met by 21.3 % (71/334) and 14.7 % (49/334) of preoperatively potent patients who received a uni- or bilateral nervesparing procedure, respectively.

589 (68.8)

Mean GHS in the study population was 70.5 ± 21.2 (median 75; IQR 58.3–83.3) pretreatment and 74.4 ± 19.7 (median 83.3, IQR 66.6–83.3) 12 months after treatment.

Qual Life Res Table 3 Surgical and medical complications of 856 patients % (n)

a

Surgical complications 14.6 (125) Prolonged catheterizationb Asymptomatic 4.3 (37) lymphoceles Blood transfusion 3.9 (34) Urinary retention 1.9 (16) after catheter removal Symptomatic 1.6 (14) lymphoceles Superficial or deep wound-dehiscence Hydronephrosis

1.1 (9)

Prolonged lymphorrhoea over drain Pelvic hematoma

0.6 (5)

Vesical tamponade Bleeding Decubitus Medical complications Urinary tract infection Supraventricular or ventricular arrhythmias Superficial or deep venous thrombosis Cardiac arrest Pneumonia Paralytic ileusc Lymphadenitis Allergy Endocarditis Priapism Acute boost of gout Pleural effusion Epididymitis Gastritis Vision impairment postoperative Oral mycosis Intermittent tachycardia

0.6 (5)

0.5 (4)

Management

Cystographic control Conservative

Transurethral catheterization or suprapubic cystostomy Percutaneous puncture and drainage or open surgical fenestration Conservative; surgical revision Conservative or percutaneous nephrostomy Conservative

0.2 (2) 0.1 (1) 0.1 (1)

Conservative or surgical revision Manual evacuation Surgical revision Conservative

2.7 (23)

Antibiotic

0.8 (7)

Medical or pacemaker implantation

0.4 (3)

Anticoagulation

0.2 0.2 0.2 0.2 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1

Reanimation, ICU Antibiotic Medical Antibiotic Medical Antibiotic Surgical Medical Medical Antibiotic Medical Conservative

(2) (2) (2) (2) (2) (1) (1) (1) (1) (1) (1) (1)

0.1 (1) 0.1 (1)

Fungicidal Conservative

A patient may have more than one complication Of all patients b Catheterization of [14 days c No productive bowel activity for 3 days postoperative requiring medical intervention or placement of a nasogastric tube a

The postoperative GHS was significantly (p \ 0.0001) higher than preoperatively (Table 4). GHS scores for patients who answered only the pre- or postoperative questionnaires are shown in Table 6. Pre- and postoperative results for GHS in patients with low- or high-grade complications compared to patients with no complications are shown in Table 4. All groups experienced an improvement of GHS after surgical treatment for prostate cancer. In regard to complications and its impact on GHS, men with high-grade complications experienced the largest improvement (mean ?7.8). Their postoperative GHS was comparable to patients who did not experience any complication (75.0 ± 19.6 vs. 75.3 ± 19.5). Patients who experienced a low-grade complication had a nearly 15 points lower GHS compared to men who met the ‘‘Pentafecta’’ criteria (71.3 ± 19.9 vs. 86.0 ± 14.2). Men who had no complication showed a GHS difference of 20 points (75.3 ± 19.5 vs. 57.3 ± 20.8) relative to their counterparts with severe incontinence. The highest GHS difference (28.2 points) was observed in patients with severe incontinence (57.3 ± 20.3) in comparison with patients who met the ‘‘Trifecta’’ or ‘‘Pentafecta’’ criteria (86.0 ± 13.6 and 86.0 ± 14.2). After controlling for potential confounding variables in the multivariate model, men with postoperative complications had an estimated mean global health score 3.993 points lower than men without complications (p = 0.015). An interaction term between complication status and baseline global health score was included in the multivariate model. The interaction was not statistically significant (p = 0.941) and removed from the model. Younger age at surgery was an independent predictor of a higher postoperative global health score (p = 0.016) as well as a lower ASA score (B2 vs. C3, p = 0.001). In the second multivariate model, men who had no complications had an estimated mean GHS 4.963 points higher than men who had low-grade complications (p = 0.003). There was no difference between men who had high-grade complications and men who had no complications (p = 0.172). Age at surgery, an ASA score C3 and ‘‘Trifecta’’ were independent predictors of GHS 1 year after surgery (p = 0.028, p = 0.001 and p = 0.001, respectively). The complete results are shown in Table 5a, b, respectively. In summary, functional outcomes showed a more profound effect on postoperative GHS relative to the impact of complications. Detailed GHS results for various aspects of our study cohort and published reference populations [21, 22] are shown in Table 6. The preoperative functional scales for physical and role function differed statistically significant between patients

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Qual Life Res Table 4 Pre- and postoperative HRQOL according to EORTC QLQ-C30 in 856 patients with or without complications All

No

Any

p*

Low-grade

p*

High-grade

p*

Mean age at surgery

63.4 ± 6.6a

62.8 ± 6.7

64.9 ± 6.1

\0.0001

64.9 ± 6.7

\0.0001

65.2 ± 5.5

0.052

Mean age at follow-up

64.8 ± 6.6

64.2 ± 6.7

66.3 ± 6.0

\0.0001

66.4 ± 6.1

\0.0001

66.6 ± 5.4

0.02

Global health score Preoperative

70.5 ± 21.2

71.4 ± 20.9

68.1 ± 21.8

0.039

67.8 ± 21.9

0.024

67.2 ± 23.2

0.322

Postoperative

74.4 ± 19.7

75.3 ± 19.5

71.7 ± 20.1

0.007

71.3 ± 19.9

0.003

75 ± 19.6

0.845

p 

\0.0001

\0.0001

0.034

0.048

0.059

Physical function Preoperative

95.5 ± 9.9

96.1 ± 9.2

94.1 ± 11.5

0.017

94.1 ± 11.4

Postoperative

90.7 ± 14.6

91.6 ± 13.9

88.4 ± 16

0.001

88 ± 16.3

0.012

94.6 ± 10.2

0.481

\0.0001

90.6 ± 13.1

0.634

p 

0.0001

\0.0001

\0.0001

90.9 ± 19.2

91.9 ± 17.6

88.2 ± 22.7

0.05

87.8 ± 23.3

0.035

92.7 ± 15.2

0.911

0.270

84.8 ± 22.4

0.187

85.4 ± 19.7

0.545

\0.0001

0.174

Role function Preoperative Postoperative

85.9 ± 22.6

86.3 ± 22.7

85.1 ± 22.3

p 

\0.0001

\0.0001

0.036

0.061

0.019

Emotional function Preoperative

70.9 ± 24.9

70.6 ± 25.3

71.4 ± 23.8

0.909

71.3 ± 24.1

0.942

73.2 ± 20.3

0.832

Postoperative

78.2 ± 23.2

78.4 ± 23.3

77.6 ± 23.1

0.497

77 ± 23.5

0.362

77.9 ± 22.4

0.706

p 

\0.0001

\0.0001

\0.0001

\0.0001

0.354

Cognitive function Preoperative

87.4 ± 18.6

87.6 ± 18.7

86.8 ± 18.3

0.319

86.3 ± 18.5

0.179

89 ± 16.7

0.794

Postoperative

85.8 ± 20

86.1 ± 19.8

85 ± 20.8

0.593

84.4 ± 21.1

0.336

86.9 ± 21.1

0.601

p 

0.044

0.179

0.086

0.067

0.372

Social function Preoperative

84.8 ± 21.5

84.9 ± 21.1

84.4 ± 22.5

0.995

83.7 ± 18.5

0.686

91.1 ± 14

0.155

Postoperative

79.5 ± 25.5

80.2 ± 25

77.7 ± 26.7

0.246

77.1 ± 27.2

0.153

79.2 ± 27.1

0.977

p 

\0.0001

\0.0001

0.001

Preoperative

5.6 ± 16.9

5.4 ± 16.5

6.1 ± 17.9

0.695

6.3 ± 18.4

0.597

3.1 ± 13

0.354

Postoperative

8.3 ± 19.6

8.3 ± 19.7

8.3 ± 19.5

0.870

8.3 ± 19.8

0.960

6.3 ± 15.7

0.689

p 

0.001

0.001

0.180

0.002

0.009

Financial difficulties

0.250

0.083

Dyspnoea Preoperative

9.9 ± 21

9.2 ± 20.4

11.6 ± 22.4

0.101

11.5 ± 22.2

0.128

14.6 ± 22.3

0.059

Postoperative

13.8 ± 24.2

13.5 ± 24.4

14.6 ± 23.7

0.234

14.6 ± 23.6

0.269

18.8 ± 23.9

0.084

p 

\0.0001

\0.0001

0.089

0.090

0.438

Insomnia Preoperative

19.1 ± 27.5

19.3 ± 27.6

18.4 ± 26.4

0.786

17.9 ± 25.7

0.738

22.9 ± 29.8

0.446

Postoperative

20.5 ± 28.1

20.9 ± 28.8

19.5 ± 26.3

0.762

19.8 ± 26.4

0.911

19.823.7

0.824

p 

0.159

0.162

0.679

0.338

0.33

Appetite loss Preoperative

4.1 ± 14.7

3.7 ± 13.9

5.2 ± 16.5

0.171

5.6 ± 16.9

0.101

0±0

0.094

Postoperative

3.2 ± 11.9

2.9 ± 11.6

3.9 ± 12.5

0.116

4.2 ± 12.8

0.067

3.1 ± 9.9

0.62

p 

0.059

0.151

0.234

Preoperative

1.3 ± 6.8

1.4 ± 7

0.9 ± 5.9

0.235

0.9 ± 6.2

0.305

0.5 ± 7.9

0.573

Postoperative

1.6 ± 7.4

1.6 ± 6.9

1.6 ± 8.7

0.091

1.7 ± 8.9

0.132

0±0

0.119

p 

0.161

0.301

0.261

0.234

0.083

Nausea and vomiting

0.261

0.317

Constipation Preoperative

3.7 ± 13.3

3.1 ± 12

5.5 ± 16.1

0.01

5.7 ± 16.9

0.008

3.1 ± 9.9

0.64

Postoperative

6.7 ± 17.6

6 ± 16.8

8.5 ± 19.6

0.056

8.7 ± 19.9

0.047

7.3 ± 14

0.255

p 

\0.0001

\000.1

0.047

123

0.059

0.157

Qual Life Res Table 4 continued All

No

Any

p*

Low-grade

p*

High-grade

p*

Diarrhea Preoperative

6.3 ± 16.4

5.9 ± 15.9

7.2 ± 17.5

0.31

7.4 ± 17.8

0.284

7.3 ± 16.4

0.527

Postoperative

6.2 ± 16.7

6.1 ± 16.3

6.6 ± 17.6

0.801

6.8 ± 17.9

0.663

3.2 ± 10

0.417

p 

0.831

0.879

0.528

0.608

0.157

Fatigue Preoperative

14.1 ± 19

13.8 ± 19.2

14.9 ± 18.7

0.158

15.3 ± 18.9

0.125

15.3 ± 15.4

0.234

Postoperative

18.7 ± 21.9

18.3 ± 21.8

19.7 ± 21.9

0.365

20.2 ± 22.1

0.197

16.7 ± 20.7

0.615

p 

\0.0001

\0.0001

\0.0001

Preoperative

10.9 ± 21.9

9.9 ± 20.6

13.6 ± 24.8

0.041

14.3 ± 25.4

0.018

7.8 ± 15.3

0.985

Postoperative

10.2 ± 20.9

9.8 ± 20.6

11.1 ± 21.9

0.497

11.5 ± 22.4

0.312

6.8 ± 13.3

0.759

p 

0.469

0.97

0.216

\0.0001

0.650

Pain

0.191

0.941

* Mann–Whitney U test (comparison of patients without complications versus any, low- or high-grade complications)  

Wilcoxon rank test (comparison of pre- versus postoperative scores)

a

All values are mean ± SD

Table 5 Results of multivariate ANCOVA for postoperative global health score and any versus none (a) and low- or high-grade complications (b)

Predictors

(a)

(b)

Estimated mean difference

SE

p

Estimated mean difference

SE

p

No

–

–

–

–

–

–

Any

-3.993

1.64

0.015

–

–

–

Low-grade

–

–

–

4.963

1.688

0.003

High-grade

–

–

–

-4.936

3.614

0.172

Complications

Confounders Age

0.238

0.111

0.033

0.245

0.111

0.028

Body mass index

-0.074

0.216

0.732

-0.092

0.216

0.669

Baseline GHS Prostate volume

0.310 -0.031

0.034 \0.0001 0.043 0.473

0.313 -0.031

0.034 \0.0001 0.043 0.236

Pelvic lymphadenectomy No

–

–

–

Yes

1.082

1.629

0.507

0.995

1.628

0.541

B2

–

–

–

–

–

–

C3

-6.194

1.836

0.001

-6.274

1.833

0.001

-15.238

4.630

0.001

-15.470

4.634

0.001

–

–

–

6.415 –

5.409 –

0.236 –

ASA score

Trifecta No Yes Pentafecta GHS EORTC QLQ-C30 global health score, ASA American society of anesthesiologists

No Yes

6.158 –

5.409 –

0.255 –

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Qual Life Res Table 6 Comparison of EORTC QLQ-C30 global health score in various clinical conditions and in reference populations Condition fulfilled Study population preoperative Study population postoperative All patients preoperative Patients with pre- but no postoperative QLQ-C30 All patients postoperative Patients with post- but no preoperative QLQ-C30 No complication postoperative Any complication postoperativea Low-grade complications postoperativea High-grade complications postoperativea Continent patients (no pad) postoperative Incontinent patients (any pad) postoperative Incontinent patients (1 pad) postoperative Severe incontinence (C2 pads) postoperative No erectile dysfunction (IIEF C17) postoperative Erectile dysfunction postoperative Missing information on postoperative erectile status No evidence of disease Positive margin or lymph node invasion or biochemical recurrence (PSA C0.2 ng/ml) Insufficient information to determine status of disease Neither Trifecta nor Pentafecta achieved postoperative Trifecta achieved postoperative Pentafecta achieved postoperative EORTC reference data—all male cancers all stages [22] EORTC reference data—all prostate cancer patients all stage [22] EORTC reference data—prostate cancer patients stage I/II [22] German general population reference data—whole cohort [21] Normative EORTC QLQ-C30 data for the German population—all males [24]

n

GHS ± SD ± ± ± ±

p*

856 856 1,171 315

70.5 74.4 70.4 70.3

21.2 – 19.7 \0.0001 21.3 21.6 0.900 

2,042 1,186

73.9 ± 19.8 73.5 ± 19.9

0.391 

621 235 221

75.3 ± 19.5 71.7 ± 20.1 71.3 ± 19.9

– 0.007 0.003

32

75.0 ± 19.6

0.845

589

78.6 ± 17.8

–

267

64.3 ± 20.5 \0.0001

170

70.5 ± 18.4 \0.0001

97

57.3 ± 20.8 \0.0001

121

83.8 ± 15.7

691 44

73.0 ± 15.7 \0.0001 69.3 ± 21.0 \0.0001

587 170

76.3 ± 18.9 – 70.3 ± 19.9 \0.0001

99 785 71 49 13,225

–

69.4 ± 22.2 \0.0001 73.0 ± 19.8

–

86.0 ± 13.6 \0.0001 86.0 ± 14.2 \0.0001 62.9 ± 23.8

3,361

68.4 ± 22.2

959

70.8 ± 20.5

889

72.7 ± 22.2

2,050

67.4 ± 23.4

* Mann–Whitney U test ‘‘–’’denotes reference group   Comparison to study population a A patient may have more than one complication and concomitant low- or high-grade complications as well

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who had no complication and those who experienced any or a low-grade complication (Table 4). After treatment, emotional function improved in each patient group. Patients with high-grade complications experienced a lower improvement of emotional function after treatment. The effect was not statistically significant, when compared to patients who experienced no complication (high-grade complication: 73.2 ± 20.3 vs. no complication: 78.4 ± 23.3; p = 0.706). The increase in emotional function in men with high-grade complications was less than five points. All other functional scales generally worsened, 1 year after surgery (details: Table 4). Social function significantly decreased by 11 points in patients who experienced high-grade complications (p \ 0.05). Compared to patients with no complication, we did not observe a difference (79.2 ± 27.1 vs. 80.2 ± 25) in postoperative social function. Detailed results of the impact of complications on functional scales are shown in Table 4. One year postoperatively, the majority of symptom scales was stable. Dyspnea, constipation, financial difficulties and fatigue significantly declined after treatment (p \ 0.001; Table 4). All values in the patient subgroups that experienced any, low- or high-grade complications showed a symptom scale change of \5 points after treatment.

Discussion We investigated the effect of complications and functional outcomes on postoperative HRQOL measured by a validated multidimensional tool 1 year following radical prostatectomy. To the best of our knowledge, this is a unique and novel study investigating the impact of complications on HRQOL, using the CDC standardized reporting methodology as compared to previous reports [3–5] as well as validated questionnaires in regard to functional outcomes 1 year after surgical treatment for prostate cancer. In summary, we found that patients did not experience a decline in quality of life 1 year after surgery relative to the baseline GHS. This suggests that radical prostatectomy as treatment option for prostate cancer, despite the risk of perioperative complications and incontinence or erectile dysfunction, does not lead to a decline of health perception due to removal of the cancer harboring gland. We could demonstrate a measurable effect of complications on various domains of the EORTC QLQ-C30. However, the clinical interpretation of these findings remains difficult. In contrast to complications, functional outcomes appear to have a more profound effect on HRQOL.

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According to our results, the group of patients without any complications and patients who experienced a highgrade complication reported the highest postoperative GHS improvement 1 year after surgery. GHS of patients who experienced low-grade complications was improved as well but to a lower degree compared to the groups mentioned above. Patients who experienced a low-grade complication were on average 2.1 years and men with highgrade complication 2.4 years older than patients who had no complication. Age also has been described as strong predictor impacting quality of life [23]. Thus, differences in preoperative GHS might be influenced by age differences between these groups as well as differences in concomitant disease, which might be reflected by a higher ASA score, resulting in a confounding bias. This is supported by the multivariate analyses. Corresponding to a previous report [20], we identified increased age, higher prostate volume and the performance of a pelvic lymphadenectomy as independent risk factors for high-grade complications in our cohort. Our data confirm previous publications [3] and demonstrate that patients who undergo radical prostatectomy and those with postoperative complications do not have an adverse quality of life in comparison with the general population [21, 24] or known prostate cancer reference groups [22]. Interestingly, high-grade complications had an impact on emotional function. Patients in this subgroup experienced an improvement of \5 points (73.2 ± 20.3 vs. 77.9 ± 22.4; p = 0.354) after surgery, whereas other groups showed a statistically and clinically significant improvement in emotional function of more than five points. Our findings may confirm results of Treiyer et al. [3] who found that absence of complications is predictive for mental health recovery. Based upon his results, the investigators recommended a mental counseling program pre- and postoperatively. Complications are frequently observed following radical prostatectomy. The utilization of validated multidimensional tools and a standardized reporting methodology enables clinicians and researchers to measure the impact of complications on QOL. We observed statistically significant differences between patients with or without complications, but we have to keep in mind their clinical meaning. According to Osaba et al. [14], changes of 5–10 points are perceived by patients as ‘‘a little change,’’ differences of 10–20 as ‘‘moderate’’ and changes of more than 20 points as ‘‘very much change.’’ In concordance with recently published guidelines for interpreting change scores of the EORTC QLQ-C30 [15], nearly all of the observed changes in global QOL or functional and symptom scales are trivial or show only a small improvement or deterioration. Thus, we agree with King [25] who stated that statistical significance should not prevail above clinical significance.

As expected, GHS was more profoundly impacted by functional outcomes compared to perioperative complications. The observed GHS values of our patient population are consistent with those reported in the published literature. Augustin et al. [26] reported a mean GHS of 71.3, 12 months after open retropubic radical prostatectomy. In his patient cohort, incontinent patients had a mean GHS of 61 compared to continent men who had a GHS of 75 and a GHS of 70 in patients who experienced an erectile dysfunction. Giberti et al. [27] reported a mean GHS of 78 in 100 patients 1 year after open retropubic radical prostatectomy. However, impact of incontinence and erectile dysfunction on GHS was not reported in this study. Only the aforementioned study by Augustin et al. [26] used the EORTC QLQ-C30 to measure the impact of functional outcomes on general health perception. Consistent with other publications, which used different tools to evaluate quality of life [28–30], adverse postoperative outcomes such as incontinence, erectile dysfunction, persistent disease (e.g., lymph node metastases and positive margins) or biochemical recurrence led to a decrease in HRQOL in our study cohort. Patients who met the ‘‘Trifecta’’ [1] or ‘‘Pentafecta’’ [2] criteria experienced the best postoperative quality of life (GHS 86.0 ± 14.2 and 86.0 ± 13.6). Thus, both, ‘‘Trifecta’’ and ‘‘Pentafecta,’’ seem to be useful outcome definitions including patients with the highest likelihood to perceive a high quality of life after surgical treatment. Although Pentafecta in contrast to Trifecta outcome was not shown to be an independent predictor of postoperative global health perception in the multivariate model, both seem to be useful outcome definitions in regard to patients who have the highest likelihood to perceive high quality of life after surgical treatment. Our study has several limitations. After discharge, an additional 0.6 % [9] to 14.1 % [31] of adverse events might occur within 90 days postoperatively, representing the commonly accepted time period for postoperative complications. Unfortunately, we cannot provide this information. Another important drawback is the assumption that the effect of perioperative complications on HRQOL might be time dependent resulting in a limited impact on HRQOL 1 year after treatment. Additionally, concerning the latter limitation, the response shift bias [32] has to be taken into account; especially, patients who suffered from high-grade complications may perceive their quality of life different from patients who did not experience any complication. A significant proportion of our total patient cohort was not included into analysis due to missing questionnaires. Interestingly, the majority of patients (60 %) decided not to return the questionnaires 1 day prior to treatment. During follow-up, 80 % returned the questionnaires. Several reasons may account for this: On

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admission day, the patient has to get through a panel of clinical examinations (electrocardiomyography, stress-test electrocardiomyography, pulmonary function analysis, chest X-ray, excretory urography, ultrasound and clinical examinations and anesthesiology examination) and may not find the necessary time and privacy to answer several— in part intimate—questionnaires. Next to this, patients may be under immense psychological stress on the day before major cancer surgery and therefore choose not to answer the questionnaires. At last, the most part of our patients is not seen in the outpatient setting before surgery which would make it possible, to hand out our questionnaire set earlier. To identify a possible selection bias, a statistical comparison of all patients including those who did not return pre- and/or postoperative questionnaires was performed and showed no difference between the groups (Tables 2, 6). No significant differences in demographic, clinical and histopathological parameters, GHS scores and incidence of complications were observed, suggesting that the study population is a representative subgroup for the entire cohort. Nevertheless, evaluation of parameters impacting quality of life remains challenging as true quality of life is presumably affected by multiple confounding parameters such as educational, socioeconomic,

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marital status or co-existing diseases. These parameters, however, were not assessed in our patient population.

Conclusions Radical prostatectomy does not lead to a decline of general global health perception in patients suffering from prostate cancer. Adverse surgical outcomes have a statistically measurable impact on quality of life; however, the clinical impact 1 year after radical prostatectomy is trivial. Functional outcomes as well as age and ASA score have a large clinical effect on health perception. Patients who fulfill the combined ‘‘Trifecta’’ or ‘‘Pentafecta’’ outcome criteria have the highest likelihood to perceive the best quality of life after surgical treatment. Validated, standardized tools should routinely be applied to assess QOL in patients treated surgically for prostate cancer.

Appendix: Questionnaire for patients after open retropubic radical prostatectomy

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