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Long-term quality of life among localised prostate cancer survivors: QALIPRO population-based study

European Journal of Cancer, August 2016, Pages 143 - 153

Abstract

Background

To evaluate quality of life (QoL) 10 years after treatments for localised prostate cancer (LPCa) patients in comparison with aged-matched healthy controls.

Methods

LPCa patients diagnosed in 2001 were obtained from 11 French cancer registries. Controls were recruited among the general population and were matched to patients on age and geographic area. EORTC Quality of Life Questionnaire – Core 30 items, Expanded Prostate Cancer Index Composite, Hospital Anxiety and Depression Scale and Multidimensional Fatigue Inventory self-reported questionnaires were used to measure QoL, anxiety and fatigue. Patients were classified in three groups according to previous treatments: radical prostatectomy (RP), radiotherapy (RT) and radical prostatectomy and radiotherapy (RP+RT). The differences in QoL between patients and controls and according to treatment groups were evaluated.

Results

There were 287 patients and 287 controls. There was no socio-demographic difference between patients and controls. Treatments were: RP (143), RT (78), PR+RT (33), baseline hormone therapy (49) and hormone therapy at the time of the study (34). Patients had similar levels of global QoL, anxiety, depression and fatigue as controls. They reported more urinary troubles (urinary function and incontinence) (p < 0.0001) and more sexual dysfunctions (p < 0.0001) than controls, whatever the treatment group. Worse bowel dysfunction was reported in patients treated by RT and RP+RT (p < 0.002). According to the treatments, RP groups had the worst urinary function and incontinence (p < 0.01), and reported more bowel bother when the treatment was combined with RT.

Conclusions

Even though patients reported similar global QoL as control 10 years after treatment, patients reported numerous urinary and sexual dysfunctions. Patients treated with RP+RT reported cumulative sequelae of both treatments.

Highlights

  • Ten years after treatment, patients reported similar global quality of life than controls.
  • Nevertheless, they presented persistent urinary, bowel and sexual adverse effects.
  • Patients treated with radical prostatectomy and radiotherapy reported cumulative sequelae of both treatments.

Keywords: Quality of life, Localised prostate cancer, Long survivors, Population based study.

1. Introduction

Prostate cancer (PCa) is one of the most frequent cancers in developed countries and represents nearly a quarter of all cancers diagnosed in men in France [1]. Improvements in cancer treatments and early diagnosis have led to an increased number of long-term PCa survivors.

Patients with localised prostate cancer (LPCa) have different curative treatment options such as radical prostatectomy (RP), radiotherapy (RT) or both. Androgen deprivation therapy can also be proposed in combination with the others treatments [2]. LPCa patients have a long-term survival and treatments often induce acute and delayed toxicities and sequelae that impact quality of life (QoL). Toxicities may differ according to the treatment used [2].

While many studies have identified adverse effects of PCa treatments, some focused on short (1–3 years) or intermediate-term follow-up (4–5 years) and most of them focused only on symptoms. Some have assessed the impact of treatments in the long-term (>5 years) [3], [4], [5], [6], [7], [8], and [9] but few of them included assessment of different domains of QoL and fatigue, that could be impacted. Moreover, only three studies compared QoL and/or symptoms of patients to those of healthy controls [3], [4], and [5]. Since the 10-year net survival rate is equal to 71% [10], a careful evaluation of long-term QoL and sequelae in LPCa patients in comparison to those of healthy men of the same age is crucial. This allows to better understand the issues involved and inform patients of the potential long-term consequences of the different treatments. This French population-based study evaluated QoL and sequelae 10 years after treatments for LPCa in comparison with those of aged-matched controls.

2. Methods

2.1. Study design and participants

QALIPRO is a population-based case-control study conducted in 2011 among long-term PCa patients survivors initially enrolled in a large cohort from the French network of cancer registries including 2181 patients with a diagnosis of PCa in 2001 from 11 French cancer registries [11]. Inclusion criteria were as follows: i) age >40 at diagnosis, ii) LPCa, low or intermediate D'Amico risk classification, iii) alive but no clinical or radiological relapse (except isolated rising PSA), iv) no history of other cancer except basal cell skin carcinoma.

Controls were selected from the general population covered by the 11 cancer registries. They were randomly selected from electoral rolls in each geographic area and were matched with patients for age (±2 years). Males having a history of cancer (except basal cell skin carcinomas) were excluded.

2.2. Procedure

The project was approved by the local ethics committee, the French Advisory Committee on Information Processing in Material Research in the Field of Health (CCTIRS) and by the National French Data Protection Authority (CNIL). Patients and controls were approached by mail to participate in a study with self-reported questionnaires. Data collection started in September 2011. Subjects were mailed a package including an information letter, the questionnaires, and a postage-paid return envelope. A reminder was sent after 1 month if necessary.

2.3. Patient-reported outcomes (PROs)

A self-administered questionnaire was sent to the patients and the controls. It included socio-demographic characteristics and standardised validated instruments assessing global and disease-specific QoL, anxiety and depression and fatigue. We used the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 item (EORTC QLQ-C30) to provide measure of general QoL and the Expanded Prostate Cancer Index Composite (EPIC) to provide disease-specific aspect of QoL [12] and [13]. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS) and fatigue was evaluated using the Multidimensional Fatigue Inventory (MFI) [14], [15], [16], [17], and [18].

According to the scoring instruction, a linear transformation was used to standardise raw scores on a 0–100 scale (for QLQ-C30, EPIC and MFI). For functional scales, higher scores representing higher levels of functioning (five dimensions in the QLQ-C30, EPIC). For symptom scales, higher scores represented higher levels of symptomatology or problems (nine dimensions in the QLQ-C30, MFI).

In addition, we collected information about family, socio-professional status and comorbidities using a questionnaire for living conditions used in previous surveys [19] and [20]. This questionnaire included items on education level, marital status, employment, and use of medical services.

2.4. Medical information

For all eligible patients, initial clinical data at diagnosis (2001) were obtained from medical records collected by the registries and update in 2011 for the follow-up, which included clinical stage, histology, D'Amico risk classification, modalities of therapy, Charlson comorbidity index and follow-up.

2.5. Cancer treatment

Patients received various modalities of treatments. We categorised the modalities of treatment into three groups: RP (n = 143), RT (n = 78) and combined treatment, which included patients who had received radical prostatectomy and radiotherapy (RP+RT, n = 33). Whatever the treatment group, 49 patients received initial androgen deprivation therapy (ADT) and 34 patients had ADT at the time of the study. Patients who had received only ADT (n = 12), endoscopic resection (n = 9), ultrasonography (n = 1) and no treatment (n = 11) were excluded from treatment-modality analyses.

2.6. Statistical analysis

Among patients, comparison between participants and non-participants on age and medical variables were performed using χ2 tests and t-tests. Comparison of socio-demographic characteristics and medical use between patients and controls were performed with a paired t-test for quantitative variables and the McNemar χ2 for categorical variables.

In order to identify medical and socio-demographic variables significantly linked to QoL scores, we performed a multivariate analysis of variance (ANOVA). Age, education level, marital status, lives alone, employment status, monthly income, medical consultation during the past 12 months, chronic disease and regular medication were tested initially by bivariate analysis then multivariate ANOVA with Bonferroni correction. Then, we performed a multivariate ANOVA in order to compare QoL scores between patients and controls, adjusting for the medical and socio-demographic variables linked to scores in the previous step. Likewise, we performed a multivariate ANOVA in order to compare QoL scores between treatment modalities and the group of controls, adjusting for the medical and socio-demographic variables linked to scores. A supplementary analyse was made, only on patients, for checked current ADT effects. For this, ADT was added to adjustment variables.

Missing data for component items of QoL scores were treated according to published rules of the different questionnaires [21] and [22].

Based on the variability of scores reported in QoL studies, our study was designed to be able to detect a difference at least of ten points on a scale ranging from 0–100, when the standard deviation of the difference was equal to 40. With an alpha risk of 1% and 90% power, we calculated that 242 patients needed to be recruited.

For all PROs questionnaires (except HADS), a difference of 5–10 units on a scale ranging from 0–100 was considered as small, a difference of 10–20 units was considered as moderate, and a difference >20 units was considered as large, according to the recommendations [23], [24], and [25]. Given the large number of comparisons, we applied a p-value <0.01 in order to minimise type 1 error. Analyses were performed using SAS version 9.3 (SAS Institute, Cary, NC). All reported P-values are two-sided.

3. Results

3.1. Study population

We identified 646 eligible patients. Of these, 317 completed the questionnaire. Among the 2855 controls contacted, 683 completed the questionnaire (Fig. 1). The participation rate of all eligible subjects was 49.1% for patients and 23.9% for controls. After exclusions due to relapse or other cancer, 287 questionnaires of patients and 287 questionnaires of aged-matched controls were exploited in the final analyses.

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Fig. 1

Flowchart of study population.

 

Among patients, participants (n = 317) were younger than non-participants (n = 329) (65.7 years versus 68.8 years; p < 0.0001) and they had fewer comorbidities at diagnosis (81% of participants have no comorbidities versus 72%; p = 0.009). Controls were randomly age-matched to patients (±2 years). There was no statistical significant difference in initial PSA, D'Amico classification, Gleason score or clinical stage between participants and non-participants.

3.2. Population characteristics

Socio-demographic characteristics and medical consumption (medical consultations and use of medication) are presented in Table 1. There were no significant socio-demographic differences between the two groups. The mean age was 76 years. They were no significant differences in use of medical services, frequency of chronic disease and regular medication except for sedative consumption, where patients consumed more tranquilisers than controls.

Table 1

Socio-demographic characteristics and medical consumption of localised prostate cancer patients and controls.

 

Patients (n = 287) Controls (n = 287) p-value
n (%) n (%)
Age (years) median (min–max) 75.8 (61–91) 76.5 (59–91) 0.515
Education level 0.713
 Low 67 (24.9) 57 (21.2)
 Middle 116 (43.1) 125 (46.5)
 High 86 (32.0) 87 (32.3)
Marital status 0.437
 Single 4 (1.5) 10 (3.6)
 Married/in a couple 232 (84.4) 222 (80.7)
 Separated 10 (3.6) 13 (4.7)
 Widowed 29 (10.5) 30 (10.9)
Housing 0.594
 Tenant 18 (6.5) 25 (9.1)
 Owner 240 (87.3) 237 (86.2)
 Lodging/ retirement home 17 (6.2) 13 (4.7)
Lives alone 26 (9.7) 37 (13.9) 0.161
Monthly income (euros) 0.913
 0–750 11 (4.7) 11 (4.7)
 750–1500 57 (24.4) 62 (26.5)
 1500–3000 112 (47.9) 115 (49.1)
 > 3000 54 (23.1) 46 (19.7)
Employment status 0.999
 Employed 6 (2.1) 7 (2.5)
 Retired/house husband 275 (97.9) 274 (97.5)
Consultation during past 12 months
 No doctor 5 (1.9) 8 (3.0) 0.581
 General practitioner 247 (93.6) 253 (95.8) 0.327
 Number of times GP means (std) 4.8 (3.0) 4.4 (3.1) 0.227
 Specialist 141 (53.4) 161 (61.0) 0.088
 Number of times specialist means (std) 2.6 (1.9) 2.6 (1.8) 0.893
Chronic disease
 No known chronic disease 48 (22.5) 46 (21.6) 0.906
 Heart failure 39 (18.3) 37 (17.4) 0.899
 Respiratory failure 17 (8.0) 17 (8.0) 1.000
 Hypertension 77 (36.2) 79 (37.1) 0.923
 Diabetes 24 (11.3) 37 (17.4) 0.092
 Arthritis or other joint disease 71 (33.3) 70 (32.9) 1.000
 Autoimmune disease 2 (0.9) 3 (1.4) 1.000
 Other 31 (14.6) 21 (9.9) 0.164
Regular medication 244 (91.7) 225 (84.6) 0.011
 Sleep medication 29 (11.3) 23 (9.0) 0.471
 Tranquilisers 20 (7.8) 4 (1.6) 0.002
 Hypertension medication 124 (48.4) 116 (45.3) 0.533
 Heart medication 87 (34.0) 71 (27.7) 0.149
 Pain medication 39 (15.2) 44 (17.2) 0.645
 Prostate medication 58 (22.7) 48 (18.8) 0.302
 Other drugs 76 (29.7) 75 (29.3) 1.000

Significant difference (p < 0.01).

Abbreviations: GP, general practitioner; std, standard deviation.

There were no differences between the three treatment groups concerning clinical characteristics except for the Gleason score (p < 0.01), which was higher in the combined treatment group (Table 2). Thirty-four were being treated with ADT at the time of the study (2011).

Table 2

Clinical characteristics of localised prostate cancer patients according to initial treatment modality.

 

RP (n = 143) RT (n = 78) RP + RT (n = 33) p-value
n (%) n (%) n (%)
Age at diagnosis (years) median (min–max) 64.0 (41–73) 66.9 (54–78) 64.5 (53–74) <.0001
PSA 0.705
 <4 ng/ml 8 (5.6) 5 (6.4) 2 (6.1)
 4–10 ng/ml 88 (61.5) 42 (53.8) 16 (48.5)
 10–20 ng/ml 45 (31.5) 29 (37.2) 15 (45.4)
 Unknown 2 (1.4) 2 (2.6) 0 (0.0)
Charlson comorbidity index 0.899
 0 115 (80.4) 65 (83.3) 28 (84.9)
 1–2 27 (18.9) 12 (15.4) 5 (15.2)
 ≥ 3 1 (0.7) 1 (1.3) 0 (6.1)
TNM 0.022
 T1 72 (50.4) 33 (42.3) 8 (24.2)
 T2 71 (49.7) 45 (57.7) 25 (75.8)
Gleason score 0.003
 2–6 80 (55.9) 53 (68.0) 13 (39.4)
 7 54 (37.8) 21 (26.9) 16 (48.5)
 8–10 8 (5.6) 0 (0.0) 4 (12.1)
 Unknown 1 (0.7) 4 (5.1) 0 (0.0)
D'Amico risk classification 0.102
 Low 43 (29.6) 16 (20.5) 3 (9.1)
 Intermediate 100 (70.4) 62 (79.5) 30 (90.9)
ADT in 2001 <.0001
 Yes 8 (5.6) 35 (44.9) 6 (18.2)
 No 135 (94.4) 43 (55.1) 27 (81.8)
ADT in 2011 0.114
 Yes 14 (11.1) 13 (19.7) 7 (22.6)
 No 129 (90.2) 65 (83.3) 26 (78.8)

Significant difference (p < 0.01) are shown in bold.

Abbreviations: RP, radical prostatectomy; RT, radiotherapy; RP+RT, radical prostatectomy and radiotherapy; PSA, prostate-specific antigen; TNM, tumour node metastasis; ADT, androgen deprivation therapy.

3.3. Comparison of PROs between PCa survivors and controls (Table 3)

There were no differences between patients and controls in all the domains of QoL (QLQ-C30). Whereas patients reported more constipation than controls but this was not clinically relevant (<5 points). There was no difference concerning fatigue.

Table 3

Quality of life scores of localised prostate cancer patients and controls.

 

Patients (n = 287) Controls (n = 287) p-valuea Mean differencef
Meane (SE) Meane (SE)
QLQ-C30
 Physical functioning 84.5 (1.4) 83.7 (1.4) 0.610 0.8
 Role functioning 85.0 (1.7) 86.3 (1.7) 0.483 −1.4
 Emotional functioning 82.8 (1.2) 86.9 (1.2) 0.017 −4.1
 Cognitive functioning 81.9 (1.2) 82.1 (1.2) 0.920 −0.2
 Social functioning 86.8 (1.4) 90.5 (1.4) 0.057 −3.7
 Global health status/ QoL 71.8 (1.2) 74.6 (1.2) 0.092 −2.8
 Fatigue 20.8 (1.4) 19.1 (1.4) 0.360 1.7
 Nausea and vomiting 1.7 (0.4) 1.7 (0.4) 0.928 0.0
 Pain 13.5 (1.4) 17.7 (1.4) 0.038 −4.2
 Dyspnoea 20.7 (2.2) 18.1 (2.1) 0.250 2.6
 Insomnia 24.3 (1.7) 19.6 (1.7) 0.047 4.8
 Appetite loss 5.8 (0.9) 4.3 (0.9) 0.280 1.4
 Constipation 15.1 (1.3) 10.2 (1.3) 0.008a 4.8
 Diarrhoea 8.6 (1.0) 6.0 (1.0) 0.055 2.6
 Financial difficulties 6.6 (1.2) 7.5 (1.2) 0.538 −0.9
MFI
 General fatigue 31.5 (1.8) 27.6 (1.7) 0.037 3.9
 Physical fatigue 31.4 (2.1) 28.1 (2.0) 0.122 3.3
 Mental fatigue 30.2 (2.6) 26.8 (2.4) 0.073 3.4
 Reduced activity 40.0 (2.7) 36.3 (2.5) 0.053 3.8
 Reduced motivation 31.6 (2.6) 30.2 (2.4) 0.468 1.4
EPIC
 Urinary 79.8 (1.0) 86.1 (1.0) <.0001a −6.3b
 Urinary function 85.2 (0.9) 94.9 (0.9) <.0001a −9.7b
 Urinary bother 76.3 (1.2) 80.3 (1.2) 0.013 −4.0
 Irritative/obstructive 83.0 (0.9) 84.4 (0.9) 0.260 −1.4
 Incontinence 76.1 (1.5) 91.7 (1.5) <.0001a −15.7c
 Bowel 89.9 (1.3) 92.3 (1.3) 0.039 −2.4
 Bowel function 91.1 (1.0) 93.0 (0.9) 0.026 −1.9
 Bowel bother 88.4 (2.0) 90.4 (1.9) 0.244 −2.0
 Sexual 37.9 (2.6) 54.5 (2.6) <.0001a −16.6c
 Sexual function 31.9 (3.6) 55.4 (3.5) <.0001a −23.4d
 Sexual bother 50.1 (6.0) 50.8 (5.8) 0.837 −0.7
 Hormonal 88.8 (1.2) 92.1 (1.1) 0.010 −3.3
 Hormonal function 89.7 (1.1) 92.3 (1.0) 0.026 −2.6
 Hormonal bother 88.5 (1.5) 91.6 (1.4) 0.047 −3.0

a Significant difference (p < 0.01).

b Small clinically relevant differences.

c Moderate clinically relevant differences.

d Large clinically relevant differences.

e Adjusted scores.

f Computed as adjusted mean (patient) – adjusted means (controls).

Abbreviations: QLQ-C30, EORTC Quality of Life Questionnaire – Core 30 items; MFI, multiple fatigue inventory; EPIC, Expanded Prostate Cancer Index Composite; QoL, quality of life; SE, standard error.

Scores range from 0–100, for functional scales, higher scores representing higher levels of functioning (five dimensions in the QLQ-C30, EPIC). For symptom scales, higher scores representing higher levels of symptomatology or problems (nine dimensions in the QLQ-C30, MFI).

Concerning disease-specific QoL (EPIC), patients presented more urinary disorders than controls (urinary dysfunction and incontinence). They also had more sexual troubles, especially sexual dysfunction. These disorders had a significant clinical difference (all the differences were >15 points). Despite considerable functional decline, urinary and sexuality bother scores were not different between patients and controls. Patients tended to have more hormonal disorders although the difference was <5 points.

Long-term patients did not express any more anxiety or depression than controls (results not shown); mean score was 5.0 and 4.5 for anxiety and 4.9 and 4.4 for depression in patients and controls respectively (HADS, p > 0.05).

According to treatment groups, in comparison to controls (Fig. 2), patients treated with RP±RT had worse urinary summary scores, especially in urinary function and incontinence scores. Scores of patients treated with RT were not different from those of controls for incontinence but were lower for urinary function (score = 89.9 versus 95.3). Bowel disorders were reported among patients treated with RT and RP+RT. Moreover, patients treated with combined RP+RT reported bowel bother (score = 74.0 versus 91.1 for controls).

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Fig. 2

EPIC quality of life score of according to treatment. Controls are shown in green. At the top, global p-value for the subscale. A. Urinary domain. B. Bowel domain. C. Sexual domain. D. Hormonal domain. Abbreviations: RP, radical prostatectomy; RT, radiotherapy; RP+RT, radical prostatectomy and radiotherapy. * Androgen deprivation therapy in 2011: RP = 11.1%, RT = 19.7%, RP+RT = 22.6%.

 

All the patients presented sexual dysfunction whatever the treatment. Bother related to ADT were mainly reported in patients treated with RP+RT, explicated by the fact that 23% of them were receiving ADT at the time of the study.

3.4. Comparison of prostate-specific PROs between the treatments groups

When QoL was compared between the different treatment groups, patients treated with RP±RT had worse urinary dysfunction and incontinence than those treated only by RT. Patients treated with the association of RP+RT had a worse summary bowel score than those treated only with RP (p < 0.0001). The range of sexuality impairment was the same in the three groups.

Concerning symptoms related to ADT, no difference was observed between the three groups with regards to functioning but patients treated with PR+RT reported more bother. However, after adjustment on current ADT, the hormonal dimension was the same whatever the treatment group (results not shown).

Patients treated by ADT (in 2011) had more hormonal disorders than other patients. They also had worse sexual function (Table 4).

Table 4

Quality of life of prostate cancer survivors according to androgen deprivation therapy at the time of study.

 

ADT in 2011 (n = 34) No ADT (n = 220) p-valuea Means differencee
Meand (SE) Meand (SE)
EPIC
 Urinary 81.0 (2.9) 79.5 (1.5) 0.643 1.5
 Urinary function 88.2 (2.9) 82.6 (1.4) 0.083 5.6
 Urinary bother 76.0 (3.2) 76.8 (1.7) 0.810 −0.8
 Irritative/obstructive 82.3 (2.4) 83.2 (1.3) 0.737 −0.9
 Incontinence 80.1 (4.5) 73.9 (2.3) 0.209 6.2
 Bowel 91.1 (2.3) 85.5 (1.2) 0.030 5.6
 Bowel function 92.0 (1.8) 88.1 (0.9) 0.049 3.9
 Bowel bother 90.9 (3.3) 83.5 (1.6) 0.042 7.4
 Sexual 21.4 (2.8) 26.2 (1.3) 0.110 −4.8
 Sexual function 4.2 (3.4) 14.5 (1.6) 0.005a −10.3c
 Sexual bother 64.9 (7.9) 54.0 (3.7) 0.191 10. 9
 Hormonal 78.6 (2.7) 88.8 (1.3) 0.001a −10.2c
 Hormonal function 81.1 (2.6) 88.1 (1.3) 0.013 −7.0
 Hormonal bother 78.4 (3.2) 88.1 (1.6) 0.005a −9.7b
QLQ-C30
 Physical functioning 82.2 (74.9) 80.5 (74.8) 0.570 1.7
 Role functioning 77.9 (4.3) 81.5 (2.6) 0.428 −3.6
 Emotional function 84.7 (3.6) 81.8 (1.7) 0.460 2.9
 Cognitive functioning 79.5 (3.5) 84.0 (1.8) 0.222 −4.5
 Social functioning 84.2 (3.8) 84.6 (1.9) 0.937 −0.4
 Global health status 87.8 (7.6) 86.3 (6.8) 0.666 1.5
HADS
 Anxiety 5.6 (2.8) 6.2 (3.5) 0.289 NA
 Depression 5.5 (3.1) 5.2 (3.9) 0.658 NA

a Significant differences (p<0.01) are shown in bold.

b Small clinically relevant differences.

c Moderate clinically relevant differences.

d Adjusted scores.

e Computed as adjusted mean (ADT in 2011) – adjusted means (No ADT).

Abbreviations: ADT, androgen deprivation therapy; NA, non applicable; QLQ-C30, EORTC Quality of Life Questionnaire – Core 30 items; SE, standard error; EPIC, Expanded Prostate Cancer Index Composite; HADS, Hospital Anxiety and Depression Scale.

Scores range from 0–100 (except for the HADS), for functional scales, higher scores representing higher levels of functioning (five dimensions in the QLQ-C30, EPIC).

4. Discussion

To our knowledge, this is one of the first large population-based studies to analyse all the aspects of long-term QoL and symptoms 10 years after treatments among a group of patients with LPCa in comparison to the general population. Our results obtained from registry data better reflect reality than hospital series. The patients had a global QoL similar to that of aged-matched controls. Nevertheless, they presented severe persistent urinary, bowel and sexual adverse effects, especially those who had received the combined treatment.

With time, most of the generic QoL domains in patients returned to the level of those of the general population, even if they had sequelae. These results confirm those from other long-term studies in which the generic QoL of patients was similar to that of controls or a normative sample [5], [26], and [27]. Life events other than cancer and its treatments may have more impact on the feeling of well-being in patients. Bellizzi found that some cancer survivors who reported little positive or negative impact of the disease were also coping simultaneously with the loss of vision associated with ageing, the recent loss of a loved one, and other more traumatic life events [28] and [29]. Similarly, even though long-term PCa survivors had worse scores for their general health perception in the study conducted by Mols et al., they had better scores for mental health compared with an age-matched normative sample. In that study, most patients experienced not only negative effects but also some positive effects after an encounter with a stressor [7]. Over time they adapted to their situation and managed to lead a satisfying life, thus deriving benefit from adversity [30].

Although our patients have a good global QoL compared to that of controls, they still have sequelae due to their disease and treatment. Regardless of the treatment received, the patients experienced more urinary and sexual dysfunction than controls, although they reported no more bother than controls. Findings were similar in previous long-term studies including non-cancer controls [3], [26], and [31]. In view of the functional results, we would expect that bother is worse for patients. Although they still had functional disorders, it seems they have been adapted without major bother.

Each treatment modality affects disease-specific outcomes differently. In our study, urinary dysfunction and incontinence had a greater effect on those who had undergone prostatectomy compared to controls. Patients receiving irradiation reported more long-term bowel dysfunctions. Sexual dysfunction was more frequent in patients than in controls whatever the treatment modality. These results corroborate those of previous studies [5], [26], [27], and [31].

Our patients treated with RP+RT experienced long-term toxicities of the two modalities of treatments. In comparison with patients treated only with RT, the group with the combined treatment reported worse urinary and bowel dysfunction. When they received the combination, they reported both function and bother bowel disorders. We confirm some previous results reported by other studies with shorter follow-up. Hu et al. found worse bowel and sexual function in men who received salvage radiotherapy than in those who received only prostatectomy [32]. In the SWOG trial, the PR+RT group reported more frequent urinary and bowel compromise than the RP group throughout the 5 years of follow-up, but there were no difference in erectile dysfunction between the two groups [33]. Other studies found contrary results. In one study measuring QoL after multimodal therapy with a follow-up of 21 months, patients who received RP+RT experienced a decline in urinary function. However, impact of combined treatment on urinary bother, bowel function and sexuality was no greater than in patients treated with RP alone [34]. Nevertheless, follow-up was short in that study. Three years after treatment, Formenti et al. found no significant difference in urinary and sexual function among patients treated with RP and who received postoperative RT or not [35]. However, this lack of difference may be explained by the late onset of toxicities, which ordinarily appear with a delay from the treatment, usually at least after 2–3 years after RT. Nevertheless, in comparison to the other studies, ours presents the advantage to compare patients with a long-term follow-up treated with combined therapy (RP+RT) to a group of controls. However, studies with long-term follow-up showed an early decline with some recovery in the first 2 years after treatment and thereafter a plateau or a slight decrease. Therefore, most differences between treatments seemed to be attenuated over time [6], [9], and [36].

Our study has some limitations. First, it had a case-control design and there was no prospective follow-up to evaluate the course of the disturbances over time and no know how about baseline dysfunction. Second, among the patients, non-participants were older and had more comorbidity than participants. The participation rate for the study was quite low, however it was similar to population-based studies [19], [37], [38], and [39]. We may have observed more severe sequelae than are usually encountered nowadays with modern irradiation techniques such as the conformational approach and progress with surgical techniques, which better protects the critical organs.

In summary, this population-based study provides information on all the aspects of QoL among long-term PCa survivors compared to healthy controls. Global QoL has returned to the level of the general population 10 years after diagnosis. On the other hand, functional sequelae persist such as urinary, bowel and sexual dysfunction, especially in those treated with the combined treatments RP+RT. These findings provide new insights for helping clinicians to choose treatment modalities and to inform patients of the risk of the late side-effects that may occur. This is particularly true when surgery was proposed for patients with some poor prognostic factors which could be expected to have a substantial risk of receiving this combined therapy.

Funding

This work was co-supported by grants from the ‘French National Institute of Cancer (INCa)’, the ‘Ligue Nationale Contre le Cancer’ and the ‘Fondation ARC’, (PAIR PROSTATE 2011, n°2010-176).

Conflict of interest statement

None declared.

Role of the funding source

The funding sources had no role in the study design, in the collection, analysis and interpretation of data, in the writing of the report, or in the decision to submit the article for publication.

Acknowledgements

The authors thank the physicians, the urologists and the pathologists from the 11 departments in the study. They thank the patients and controls who agreed to participate in the study.

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Footnotes

a Calvados General Tumor Registry, François Baclesse Cancer Center, Caen, France

b UMR 1086 « Cancers et Préventions », Inserm – University of Basse-Normandie, Caen, France

c Tarn Cancer Registry, Albi, France

d Claudius Regaud Institute, IUCT-O, Tarn Cancer Registry, Toulouse, France

e Quality of Life in Oncology National Platform, France

f EA 3181, SFR-FED 4234, University of Franche Comté, France

g Department of Medical Oncology, François Baclesse Cancer Center, Caen, France

h CHU Côte de Nacre, University of Basse-Normandie, Caen, France

Corresponding author: Calvados General Tumor Registry, François Baclesse Cancer Center, 3 Avenue du Général Harris, BP 5026, 14076 Caen, France. Tel.: +33 2 31 45 52 45; fax: +33 2 31 45 86 32.

1 French Network of Cancer Registries (FRANCIM): Anne-Sophie Woronoff (Doubs CR); Brigitte Trétarre (Hérault CR); Patricia Delafosse (Isère CR); Florence Molinié (Loire-Atlantique CR); Simona Bara (Manche CR); Michel Velten (Bas-Rhin CR); Emilie Marrer (Haut Rhin CR); Bénédicte Lapôtre-Ledoux (Somme CR); Anne Cowppli-Bony (Vendée CR). Note: CR = Cancer Registry.


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