Influence of achieved paternity on quality of life in testicular cancer survivors

Authors


Hannes Steiner, Department of Urology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. e-mail: hannes.steiner@uki.at

Abstract

What's known on the subject? and What does the study add?

It is known that testicular cancer, as with any malignancy, influences many different aspects of quality of life and that surgical treatment and chemotherapy negatively influence male fertility.

The study shows the importance of achieved paternity in those testicular cancer survivors with a declared wish to father a child. The study used a QoL questionnaire EORTC QLQ-TC 26 to supplement the existing QoL questionnaire QLQ-C30 of the European Organisation for the Research and Treatment of Cancer in patients with cancer.

OBJECTIVE

  • • To investigate the influence of achieved/non-achieved paternity on quality of life (QoL) in testicular cancer (TC) survivors.

PATIENTS AND METHODS

  • • We invited TC survivors treated at our department between 1989 and 2006 to complete a QoL assessment, including the European Organisation for the Research and Treatment of Cancer QoL questionnaire, EORTC QLQ-C30 (version 3.0©)/+ TC26, and follow-up questions.
  • • A total of 311 TC survivors answered the questionnaire, of whom 207 patients who did not desire paternity were excluded. The remaining 104 patients who stated a desire for paternity after TC treatment were further divided in group A (TC survivors who achieved paternity; n= 51) and group B (TC survivors who did not achieve paternity; n= 53).
  • • The data obtained were statistically analysed.

RESULTS

  • • Significant differences between groups regarding QoL were detected for social functioning (P= 0.002), emotional functioning (P= 0.001), general QoL (P= 0.018), fatigue (P= 0.025), pain (P= 0.01), sleeping problems (P= 0.024), treatment satisfaction (P= 0.039), financial aspects (P= 0.006), sexual problems (P= 0.017), body image problems (P< 0.001), dyspnoea (P= 0.005) and cognitive functioning (P= 0.019).
  • • For all scales except ‘sexual enjoyment’, patients in group A were found to have a better long-term QoL than those in group B.

CONCLUSIONS

  • • Whilst acknowledging the shortcomings in retrospective analyses, we believe our data clearly underline the important impact on QoL for TC survivors of achieved paternity.
  • • Counselling patients early at diagnosis as well as using cryopreservation of semen in all potential patients before treatment (only excluding patients definitely claiming they do not wish to achieve paternity) should therefore be regarded as the standard of care.
Abbreviations
QoL

quality of life

TC

testicular cancer

EORTC

European Organisation for the Research and Treatment of Cancer

TGCT

testicular germ cell tumour

SGCT

seminomatous germ cell tumour

NSGCT

non-seminomatous germ cell tumours

DD

detectable difference.

INTRODUCTION

Testicular cancer (TC) is the most common cancer in men aged 20–40 years [1]. Testicular germ cell tumours (TGCTs) are the most common. They are histologically classified as seminomas (seminomatous germ cell tumours [SGCTs]) and non-seminomatous germ cell tumours (NSGCTs).

Results of various European and US studies show that the incidence of TGCTs has increased in the last 30 years in Europe as well as in the USA [2,3]. In the French Midi-Pyrenees region, for example, the rate of TGCTs increased between the periods 1980–1984 and 1995–1999, a rate of ∼5.7% per year [3]. The rate for seminomas in white US men increased between 1973 and 1998 (the risk of TGCT is lower in black men), while the incidence of NSGCTs decreased. Reasons for the increase in TGCTs are largely unknown [2].

In most cases, TGCT is a curable disease, the death rate continues to decrease and the 5-year survival rate is very high, at >95% [2]; therefore, quality of life (QoL) for TC survivors is very important. After surgical removal of the primary tumour, further treatment (e.g. chemotherapy and retroperineal lymph node dissection) depends on histology and tumour stage and has a differing impact on semen quality or QoL in general [4].

Data on specific factors influencing QoL are sparse. The aim of the present study was to evaluate the influence of achieved/non-achieved paternity on QoL in TC survivors.

PATIENTS AND METHODS

After obtaining approval from the local ethical committee (study number UN3482), 615 patients with TC treated at our department between 1989 and 2006 were identified. Eight of these patients died as a primary result of TC and four patients had a benign testicular tumour and were excluded from analysis. In all, 603 TC survivors were invited to answer the QoL questionnaire the European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 [5], the TC module EORTC QLQ-TC26 [6], and other follow-up questions (Appendix 1). A total of 311 patients agreed to participate in the study and completed the questionnaire, giving an overall response rate of 51.6%. The mean (sd) age of these patients was 42.2 years, with a minimum age of 17 and a maximum age of 75 years at time of answering the questions. Of the patients who completed the questionnaire, 207 were excluded because they had no desire for paternity after TGCT therapy, while 104 patients declared a desire for paternity after treatment and formed the study group. The study group was further divided into group A, consisting of TC survivors who achieved paternity (n= 51, 49%) and group B, who did not achieve paternity (n= 53, 51%). The specific histology of the tumour (seminoma, NSGCT, mixed forms) was not a criterion for allocation to group A or B. Obtained data were analysed using spss statistical software (Table 1).

Table 1. Sociodemographic and clinical variables
 All patients, N= 104Group A: TC survivors who achieved paternity, n= 51Group B: TC survivors who did not achieve paternity, n= 53
Mean (range) age, years 39.3 (22.6–58.2)39.6 (28.5–58.2)39.0 (22.6–57.3)
Type of surgery, n (%)   
 Semicastration93 (89.4)48 (94.1)45 (84.9)
 Enucleation3 (2.9)1 (2)2 (3.8)
 Other1 (1)0 (0)1 (1.9)
 Missings7 (6.7)2 (3.9)5 (9.4)
Histology, n (%)   
 Seminom40 (38.5)21 (41.2)19 (35.8)
 Mixed41 (39.45)19 (37.3)22 (41.5)
 Other (embryonal carcinoma, choriocarcinoma)23 (22.1)11 (21.5)12 (22.6)
Tumour location, n (%)   
 Left52 (50)26 (51)26 (49.1)
 Right48 (46.2)24 (47)24 (45.3)
 Bilateral2 (1.9)1 (2)1 (1.9)
 Missings2 (1.9)0 (0%)2 (3.8)
Chemotherapy, n (%)   
 Yes66 (63.5)35 (68.6)31 (58.5)
 No38 (36.5)16 (31.4)22 (41.5)
Relapse, n (%)   
 Yes6 (5.8)2 (3.9)4 (7.5)
 No97 (93.2)49 (96.1)48 (90.6)
 Missing1 (1.0)0 (0)1 (1.9)
Mean (sd; range) body mass index 25.1 (3.7; 18.6–42.0)25.2 (3.2; 18.6–33.7)25.0 (4.2; 18.7–42)

After surgical removal of the primary tumour (orchiectomy or organ-sparing surgery, if indicated) all patients received further therapy depending on histology and tumour stage. The mean time between surgery and questionnaire assessment was 104.9 months (8.7 years), with a minimum time of 2 months and a maximum time of 449 months (37.4 years).

Patients who had recurrent TGCTs were included in the study because of results from other studies indicating similar survival rates among patients with recurrent disease to those among patients who have a primary diagnosis [7].

While answering the questionnaire patients could select ‘not at all’, ‘a little’, ‘quite a bit’ or ‘very much’. For the analyses every scale was given a value of 100 so that the results were comparable. For the functioning scales a value of 100 meant best functioning, for the symptom scales a value of 100 corresponded to strong symptoms that negatively affect a patient's QoL. A value of zero meant that the question had been answered with the minimum score. We used the method described by Osoba et al. [9] to interpret the QoL score. According to their findings, even if a result is statistically significant it does not automatically mean it is clinically relevant. They postulate that a 0–5-point difference in the QoL questionnaire is clinically ‘irrelevant’, 5–10 points show a ‘little’ difference, 10–20 points show a ‘moderate’ and >20 points an ‘important’ clinical difference (detectable difference [DD]) in QoL [8].

QUESTIONNAIRES

EORTC QLQ-C30 version 3.0© [5]: The EORTC QLQ-C30 is an internationally validated and widely accepted cancer-specific QoL instrument assessing various aspects of QoL. It comprises five functioning scales (physical, social, role, emotional and cognitive functioning), nine cancer-specific symptom scales (fatigue, nausea/vomiting, pain, dyspnoea, sleeping disturbances, appetite loss, constipation, diarrhoea and financial impact) and a global QoL scale. All scales were scored according to EORTC guidelines, resulting in a score range from 0 to 100 points.

EORTC QLQ TC 26 module [6]: The EORTC QLQ-TC26 is a supplement to the QLQ-C30 core questionnaire for the assessment of issues relevant for patients with TC. It comprises six functioning scales (satisfaction with care, future perspective, communication, satisfaction with testicular implant, sexual activity and sexual enjoyment) and six TC-specific symptom scales (treatment side effects, job problems, family problems, infertility, body image problems and sexual problems). The module was developed according to the EORTC guidelines and is now in phase IV testing.

FOLLOW-UP QUESTIONS

Patients also answered some follow-up questions (Appendix 1). Data concerning age, height, weight, recurrence, other malignancies or medical problems, paternity already achieved or existing desire for paternity and hormonal disorder were documented.

STATISTICAL ANALYSIS

Sample characteristics are given as percentages, ranges and means (sd) values. Group differences regarding achieved vs non-achieved paternity were analysed using the Mann–Whitney U- test. We used a chi-squared test to analyse the impact of various clinical variables on non-achieved paternity. Clinically important differences are reported according to Osoba et al. [8].

RESULTS

A total of 104 TC survivors reported a desire for paternity after treatment. In this cohort 49% (n= 51, group A) fulfilled their desire for paternity while 51% (n= 53, group B) were still childless. Results of QoL questionnaires are shown in Table 2. An ‘important’ clinical difference (DD >20 points) between groups A and B with regard to QoL was found in the treatment satisfaction domain, accounting for a DD of 21.7 points.

Table 2. Results of QoL questionnaire for TC survivors who achieved paternity vs TC survivors who did not achieve paternity after treatment
 Group A: TC survivors who achieved paternity, n= 51Group B: TC survivors who did not achieve paternity, n= 53 P DD
Mean (sd)Mean (sd)
  1. Values in bold font indicate significant differences (P< 0.05) between both groups.

Physical functioning96.1 (10.5)94.1 (15.9)0.5397.8
Social functioning 95.0 (13.6) 84.9 (21.7) 0.002 10.8
Role functioning96.0 (12.8)88.7 (25.9)0.13012.0
Emotional functioning 91.0 (15.1) 78.0 (22.0) 0.001 11.4
Cognitive functioning 93.7 (16.5) 88.1 (17.1) 0.019 9.7
General QoL 86.3 (16.4) 78.6 (19.6) 0.018 10.6
Fatigue 7.3 (17.3) 15.5 (22.4) 0.025 11.7
Nausea and vomiting3.0 (14.9)1.6 (5.0)0.2996.3
Pain 4.3 (16.4) 11.8 (22.9) 0.010 11.6
Dyspnoea 2.0 (10.5) 10.5 (20.5) 0.005 9.6
Sleeping problems 7.3 (16.9) 20.8 (32.2) 0.024 15.3
Loss of appetite2.0 (14.1)4.4 (13.1)0.0687.8
Constipation3.3 (10.1)3.1 (9.8)0.9235.7
Diarrhoea4.0 (10.9)8.2 (19.5)0.3089.1
Financial impact 4.7 (16.5) 15.7 (26.6) 0.006 13.1
Treatment side effects6.3 (8.3)9.6 (11.6)0.1605.7
Treatment satisfaction 84.7 (30.8) 72.1 (37.9) 0.039 21.7
Future perspective61.4 (24.2)56.7 (22.4)0.30613.2
Job problems15.0 (24.5)21.2 (24.7)0.0689.9
Family problems30.0 (21.0)39.2 (29.6)0.10115.4
Sexual activity70.7 (21.9)70.3 (20.9)0.80813.8
Sexual enjoyment83.3 (23.7)83.3 (22.6)0.47915.9
Sexual problems 6.6 (15.0) 15.4 (21.1) 0.014 10.8
Communication90.1 (18.6)82.7 (22.9)0.07813.9
Body image problems 2.0 (8.1) 23.5 (31.5) 0.000 14.4
Fertility concerns56.6 (40)67.3 (29)0.2347.8

‘Moderate’ clinical differences (DD 10–20 points) were found for: social functioning (DD = 10.8 points), emotional functioning (DD = 11.4 points), role functioning (DD = 12.0 points), general QoL (DD = 10.6 points), fatigue (DD = 11.7 points), pain (DD = 11.6 points), sleeping problems (DD = 15.3 points), financial aspects (DD13.1 points), family problems (DD = 15.4 points), sexual problems (DD = 10.8 points), body image problems (DD = 14.4 points), future perspectives (DD = 13.2 points), sexual activity (DD = 13.8 points), sexual enjoyment (DD = 15.9 points) and communication (DD = 13.9 points).

‘Little’ clinical differences (DD 5–10 points) were observed for cognitive functioning (DD = 9.7 points), dyspnoea (DD = 9.6 points), job problems (DD = 9.9 points), physical functioning (DD = 7.8 points), nausea and vomiting (DD = 6.3 points), loss of appetite (DD = 7.8 points), constipation (DD = 5.7 points), diarrhoea (DD = 9.1 points), treatment side effects (DD = 5.7 points) and fertility concerns (DD = 7.8 points).

Most importantly, on all scales TC survivors with achived paternity (group A) had better QoL scores than those who did not achieve paternity (group B). Analysis showed that tumour stage (Pearson's chi-squared test, P= 0.935) or histology (Pearson's chi-squared test, P= 0.607) had no significant association with unfulfilled desire for paternity. The number of children born after TC treatment had no statistically proven influence on QoL in group A. Furthermore we tried to analyse ejaculation disorders and low testosterone levels in correlation with QoL and found no statistically usable result because of insufficient statistical power.

We tried to exclude the role of treatment burden and detected only three differences in QoL between SGCT stage II/III and SGCT stage I (physical functioning P= 0.038/DD = 8.2, fatigue P= 0.032/DD = 10, sexual activity P= 0.043/DD = 11.4), and were not able to determine any difference between NSGCT stage I and NSGCT stage II/III at all. It seems unlikely, therefore, that more aggressive therapy causes the observed differences in QoL between groups A and B. It is more likely that paternity has this pronounced effect on QoL for TC survivors.

DISCUSSION

Cancer treatment, especially in young men, is frequently associated with fertility problems and gonadal dysfunction [9]. Patients with TC, in particular, are young and have a very high cure rate, therefore they have a higher risk of experiencing not only therapy-related short-term but also long-term side effects which can reduce their health-related QoL [10]. Although advances in treatment have contributed to extraordinarily high overall survival rates for patients with TC, the disease and/or its treatment might induce somatic long-term sequels and psychosocial morbidity, impairing QoL in the long term [11]. In this regard, the most frequent and most upsetting concerns specific to TC survivors are sexual dysfunction and fertility distress [4]; therefore, in the present study we tried to determine the effect of non-achieved paternity on the QoL of TC survivors.

Several studies have investigated the issue of fertility in patients with TC and have found a considerable rate of impaired fertility attributable to TC. Hartmann et al. [12] noted that 48% of all patients who reported a wish for children had still not fathered a child 5 years after treatment. Similar results were observed by Fegg et al. [13], who reported that 58.9% of patients with TC wished to father a child at a median follow-up time of 9.6 years after diagnosis but, of those, 53% had been unable to achieve this. The unfulfilled wish for children caused moderate to severe distress in 51.9% of those patients. Schover and Eschenbach [14] have also highlighted infertility as a major cause of anxiety in TC survivors. Anxiety about future fertility seems to be significantly higher after TC diagnosis than before and seems to continue after successful treatment [15]. Fertility problems, thus, seem to be associated with mental distress and decreased QoL [11]. Nonetheless, the impact of infertility on various QoL domains in the long term remains uncertain. In this context, the findings of the present study show impressively that various aspects of daily life (social life, family, sexuality, general Qol and job situation) are affected. By using the EORTC QLQ-C30 version 3.0©[15] and the EORTC QLQ TC 26 module [16] we have been able to detect clinically relevant QoL issues related to fertility and to show the importance of paternity for patients with TC.

It is well known that men with TC already have a sperm count ∼30% lower than the healthy male population before any treatment [16]. Moreover fertility is reduced depending on the recommended form of treatment. All available therapy regimes in patients with TC, e.g. surgery followed by radiation, chemotherapy or both, are associated with a reduction of fertility and gonadal function, as Brydøy et al. [9] show in detail in their review. Surgery such as organ-preserving operations, uni- or bilateral orchiectomy may further decrease sperm count [17] with some regeneration after 1 year if testicular tissue is left [18]. In the present study, although similar postoperative results were found in both groups after primary orchiectomy, questions concerning body image problems were rated significantly higher in group B than in group A (mean score 23.5 vs 2.0, respectively). This may indicate that the cosmetic change after loss of a testis is better accepted when the ability to procreate is maintained. Further treatment may additionally harm procreative function.

Retroperitoneal lymph node dissection has been the reason for loss of antegrade ejaculation in ∼90% of patients with TC before modifications of the surgical technique (nerve-sparing retroperitoneal lymph node dissection, modified templates) made it possible to maintain ejaculatory function [19,20]. Radiotherapy in patients with TC involves treatment of one of the most radiosensitive tissues and spermatogenesis recovers depending on radiation dose and patients age [21]. In their multicentre study, Huyghe et al. [22] investigated fertility status after TC treatment in long-term survivors. They showed in their results that fertility in patients after TC treatment decreased by 30% and that radiotherapy had a more harmful effect on fertility than chemotherapy. Lampe et al. [23] investigated 178 patients with TC who received chemotherapy, and defined risk groups for recovery of spermatogenesis according to sperm counts before the treatment, the number of cycles and carboplatin- vs cisplatin-based therapy. Because an increased rate of aneuploidy was found in semen of patients 6–18 months after treatment with cisplatin, etoposid or bleomycin, contraception should be advised for all patients with TC treated with those agents [24]. The use of contraception for 18–24 months is advised [25,26].

Although there was no significant difference in staging and treatment between groups A and B in the present study, ‘treatment satisfaction’ was rated much more highly in group A (with children) whereas ‘treatment side effects’ were similar in both groups. This highlights again that the achievement of paternity is more strongly associated in the long run with QoL issues than is the intensity of treatment. Interestingly not only the past and present, but also the subjective anticipated future seems to be influenced by the ability to father a child. For the patients in group A, ‘future perspectives’ were seen more positively and ‘family problems’ scored more favourably than in for the patients in group B.

Cryopreservation of semen before any treatment to help achieve post-therapeutic paternity is, therefore, of utmost importance for an improvement in QoL despite deteriorated fertility. Magelssen et al. [27] evaluated the role of semen cryopreservation in saving fertility in patients with TC by investigating the post-treatment paternity rate over 20 years. According to their data a considerable number of patients with TC achieved paternity without the use of semen cryopreservation, but the influence of psychological factors is undeniable and semen cryopreservation seems to be essential for assisted reproductive techniques in some survivors of TC.

The results of the present study are consistent with data obtained by Huddart et al. [28], who evaluated the influence of fertility, gonadal and sexual function on QoL in TC survivors using an EORTC QoL questionnaire and showed reduced QoL in patients with gonadal dysfunction.

One obvious limitation of the present study is its retrospective design. We invited 603 TC survivors to answer the QoL questionnaire and the response rate was 51.6%. Reasons for this high non-response rate are the long follow-up period (in some cases >20 years), address or name changing and loss to follow-up.

In conclusion, TC survivors who achieved paternity have a statistically significant better QoL and are more satisfied with their treatment compared with controls. Whilst we are aware of the common pitfalls of retrospective analyses, we believe our data clearly underline the important influence of achieved/non-achieved paternity on QoL for TC survivors. Early counselling patients at diagnosis as well as sperm cryopreservation should be offered to all patients with TC before starting any spermatotoxic treatment, even when there is no explicit wish to achieve paternity. This should be regarded as the standard of care. There should be a focus on the protection of fertility, on the reduction of gonadal toxicity and on facilitating the recovery of gonadal function.

CONFLICT OF INTEREST

None declared.

Appendix

APPENDIX 1: SPECIFIC FOLLOW-UP QUESTIONS FOR PATIENTS WITH TC

Age?
Height?
Weight?
Did you experience a tumor recurrence of your testicular cancer since your last treatment at our department?
□ No□ Yes; When?
Did a tumour on your other testical occur since your last treatment at our department?
□ No□ Yes; When?
Did another tumour occur after your testicular cancer treatment?
□ No□ Yes; what kind of tumour?: When?
Did another illness occur after your testicular cancer treatment?
□ No□ Yes; what kind of disease?: When?
Did you have children before testicular cancer treatment?
□ No□ Yes How many?
Did you wish to father a child after testicular cancer treatment?
□ No□ Yes
Did you father a child after testicular cancer treatment?
□ No□ Yes How many?
Did you have problems with your testosterone level after testicular cancer treatment?
□ No/not known/not investigated□ Yes
Hormon replacement therapy necessary?
□ No□ Yes

Ancillary