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© 2002 American Society for Clinical Oncology Quality of Life in Long-Term Survivors of Testicular Cancer: A Population-Based Case-Control StudyByFrom the Groupe Régional d’Etudes sur le Cancer (EA-1772), University of Caen-Basse, Normandie; Medical Oncology Department, Centre François Baclesse; Urology Department, University Hospital; and General Cancer Registry, Centre François Baclesse, Caen, France. Address reprint requests to Florence Joly, MD, Medical Oncology Department, Centre François Baclesse, 14076 Caen Cedex 5, France; email f.joly{at}baclesse.fr
PURPOSE: To evaluate quality of life and social problems in long-term survivors of testicular cancer. PATIENTS AND METHODS: In 1998, 71 testicular cancer survivors (cases) identified from the Calvados General Tumor Registry were enrolled onto a case-control study. One hundred nineteen healthy control subjects (controls), matched by age and location of residence, were selected at random from electoral rolls. Three self-administered questionnaires were used: two health-related quality-of-life questionnaires (Short Form-36 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 core questionnaires) and one life situation questionnaire. Specific questions concerning sexuality were also added. RESULTS: With a mean follow-up of 11 years, health-related quality-of-life scores did not differ significantly between cases and controls, nor did general symptom scores. Psychosocial problems were reported equally by cases and controls. Cases reported more modification of sexual life (P = .04) with decreased sexual enjoyment (P < .01), decreased desire (P = .02), and infertility (P < .01). Cases did not report more divorce than controls; they reported fewer changes in relationships with friends (P = .03). Although a similar proportion of cases and controls were at work, cases expressed less ambitious professional plans (P = .002). Cases had greater difficulty in borrowing from banks (P < .001). CONCLUSION: French long-term survivors of testicular cancer do not express more impairment of health-related quality of life or familial or professional life in comparison with healthy men. They did have more sexual life problems and found difficulty in borrowing from banks. This information should be used by practitioners to help their patients cope with their disease and return to normal life.
SINCE THE USE OF platinum-containing chemotherapy in combination with surgery and irradiation, testicular cancer has become a curable disease.1 Modern therapies have produced a large group of young male patients with high life expectancy who represent an ideal group for studying psychosocial factors. In the recent past, as physician interest in long-term quality of life of survivors has increased, treatment strategies aimed at reducing acute and long-term complications have been developed.2-6 These strategies include surveillance, decrease of radiation dose delivered to seminomas, and the use of equally effective but less toxic chemotherapy regimens. All treatment strategies, however, must be evaluated not only for their efficacy but also for their impact on early and long-term quality of life of patients.7-9 Since treatment-related morbidity (including chronic ototoxicity, neurotoxicity, vascular dysfunction, sexual disturbances, and infertility) does not necessarily induce impairment of quality of life,10,11 long-term evaluation of quality of life should be undertaken by the patients themselves. The use of self-administered, validated quality-of-life questionnaires is essential and should include not only questions about health-related quality of life but also questions about the patient’s family, professional, and social situation.8,12,13 Several studies have focused on quality of life after treatment using patient-reported quality of life: they have included patients from hospital series generally with a follow-up of less than 5 years. Studies of long-term survivors of 10 years or more are few.14-19 Moreover, studies in which the influence of socioeconomic and environmental factors on quality of life have been compared between patients and healthy people from the general population are rare.4,16,20 A case-control study was designed to evaluate the influence of testicular cancer and its treatment on long-term quality of life in an unselected group of patients. Testicular cancer survivors (cases) were identified from a cancer registry that has been active since 1978; they were compared with healthy men living in the same area (controls).
In September 1998, a case-control study was designed in the area of Calvados in France, in collaboration with the regional comprehensive cancer center François Baclesse, the urology department of the Caen University Hospital, and urologists from general hospitals and clinics.
Selection of Cases
Selection of Controls
Study Participation
Questionnaires Used
Characteristics of the Study Population
Statistical Analysis Tests used for comparison of means included the Mann-Whitney test and the Welch test; those used for comparison of proportions were the  2 test and Fisher’s exact test. Multiple comparisons of quality-of-life scale scores were adjusted with the Bonferroni correction. Variance-covariance analysis was used for groupwise comparisons of the SF-36 and the EORTC QLQ-C30 scores, with age and histology as covariates. Categorical variables from the life situation questionnaire that were significant after univariate analysis were included in a stepwise forward logistic regression model. For the SF-36 and the EORTC QLQ-C30 core questionnaires, missing data were treated according to published recommendations.22,24 Similar proportions of missing data (always < 10%) were observed in cases and controls. Data were stored at the Calvados General Tumor Registry using a specific database management system.33 Programs 4F, 7D, 2V, and LR of BMDP Statistical Software, Inc (Los Angeles, CA) were used to analyze the data.34
Case-Control Study Self-reported health status. Results from the SF-36 and the EORTC QLQ-C30 core questionnaires are listed in Table 3. After adjustment for family status, neither functional scales nor symptom scales differed between cases and controls in either questionnaire. Financial difficulties were uncommon in both groups (8% of cases and 11% of controls).
Family and social life. The third questionnaire evaluated the influence of previous history of testicular cancer on familial, sexual, social, and professional life. An attempt was also made to measure the use of medical services. The most important items related to familial, sexual, social, and professional problems are listed in Tables 4 and 5.
Family and sexual relationships. At the time of interview, cases and controls had similar marital status (Table 1). Among individuals who were married or lived as a couple at the time of diagnosis (for cases) or the reference date (for controls), 13% of cases and 16% of controls experienced separation or divorce (P = .7), suggesting that testicular cancer had no influence on the probability of separation. More cases, however, reported modification in their sexual life than did controls (49% v 33%, P = .04). This was due mainly to a decrease of sexual enjoyment and desire. Cases also reported more infertility (P < .001) and more ejaculation dysfunction (P = .07) and erectile dysfunction (P = .05) than controls did. A similar proportion of cases and controls had children (80% and 88%, P = .14). Fifty of the cases had children before diagnosis of cancer, and seven (14%) of them had children after their disease was treated. Among the 21 cases without children before diagnosis of cancer, five (24%) had children after diagnosis and treatment and 16 did not because they were single (14 cases) or had treatment-related sterility (two cases). Social life. Changes in relationships with friends were less frequent in cases than in controls (P = .03), with loss of friends reported by 8% and 18%. Cases reported less modification in their day-to-day leisure activities than controls (19% v 42%, P = .001), and they did not report more changes in their social activity than controls. Cases and controls expressed similar difficulties in professional life. Of those at work at the time of interview, 28% of cases and 29% of controls had experienced changes in their employment, and 8% in both groups worked part-time. The proportions of cases and controls who were not working during the period from 1997 to 1998 were similar (29% v 26%, P = .7). Among subjects not at work, 11 of 17 cases had retired, two were unemployed, and four had chronic illness; in controls, 19 of 28 had retired, five were unemployed, and four had chronic illness. In response to the question "was your professional life modified?" cases reported less professional ambition than controls did (P = .002). The most important social difficulty reported by cases was the problem of borrowing from banks. Overall, 31% of cases reported problems in borrowing from banks (additional charges, refusal to give credit, and so on) as compared with 2% of controls (P < .001), even after adjustment for income level and professional status. Moreover, one third of cases reported difficulties more than 10 years after their cancer was cured, and all cases who reported problems in borrowing from banks indicated that it was due to their cancer history. Use of medical services in the 6-month period before interview. Use of medical services was assessed by the following: frequency of visits to a general practitioner or specialist practitioner(s), hospitalization, blood withdrawal, radiographic examinations, and consumption of medication. Consumption of medication was similar in both groups, with 46% of cases and 43% of controls taking medication, mainly sleeping pills (8% v 3%) and tranquilizers (13% v 8%). Visits to practitioners were reported by 40% of cases and 34% of controls (P = .51). The proportions of cases and controls who had blood withdrawal or radiographic examinations were also similar. Multivariate analysis. A stepwise forward logistic regression was undertaken, including all family and social parameters that were found to be statistically significant by univariate analysis. Regression showed that problems borrowing from banks (odds ratio [OR] = 36.3; 95% confidence interval [CI], 7.13 to 185, P < .001), changes in relationships with friends (OR = 3.82; 95% CI, 1.25 to 11.7, P = .018), and changes in sexual life and enjoyment (OR = 2.8; 95% CI, 1.13 to 7.06, P = .023) were associated with cases.
Analysis Specific to Cases
Cases were grouped according to their score on the fatigue scale (EORTC QLQ-C30 core questionnaire): 0 to 19 (almost normal), 20 to 39, and Impact on sexuality. Almost half of the cases (49%) indicated modifications in their sexual life since diagnosis and treatment of the disease (with similar proportions in the three treatment groups), as compared with 33% of controls (P = .04). They complained mainly about decreased sexual enjoyment and desire (Table 5). In addition, 16% of cases reported infertility, whereas there was none among controls (P < .001). While three cases had fertility problems before treatment, 11 additional cases reported infertility at the time of interview (seven were given chemotherapy and four received radiation therapy). Of these, eight had children and three wanted to have children. Other difficulties concerned sexual performance. Seventeen cases (25%) reported erectile dysfunction, 12 of whom (median age at interview, 52 years) were irradiated for seminoma. Ten cases (15%) reported dysfunction in ejaculation. Among the 22 cases who had lymph node dissection, five (23%) developed dysfunction of ejaculation as compared with five (12%) of the 41 cases who had not (P = .3). Forty-seven percent of cases had a testicular prosthesis. Physical and psychologic acceptance was good, with only four cases considering the prosthesis as a handicap in their intimate relationships and one case considering it a handicap in his day-to-day life. The presence or absence of a testicular prosthesis had no significant impact on sexual life; however, impairment of desire tended to be more frequent in cases without a prosthesis (seven of 34, or 21%) than in those who had one (two of 37, or 5%) (P = .077).
Acceptance of the survey. Eighty-three percent of cases judged that the study to collect more information on long-term quality of life was important to prevent difficulties for new patients. The questionnaire helped "recognition of personal things" for 9% of cases. In contrast, the experience was negative for only 7% of cases.
Our data confirm that long-term survivors of testicular cancer cope with the consequences of the disease. They do not express impairment of health-related quality of life or of family or professional life in comparison with healthy men. However, impairment of sexual life and fertility represent the main physical long-term sequelae. In addition, difficulty in borrowing from banks is viewed as the most serious social problem even more than 10 years after the patient’s disease was cured. The selection of quality-of-life questionnaires remains difficult for multiple reasons. Questionnaires must be validated for both a healthy population and for cancer patients. A translation to the spoken language of the target population must be available. Specific information about problems such as fertility and sexuality has to be collected because no specific module on testicular cancer is available. The two health-related quality-of-life questionnaires (SF-36 and EORTC QLQ-C30) were selected because they have been validated in a general population, validated French translations are available, and studies have been conducted among long-term cancer survivors indicating that the questionnaires have good properties in that situation.21-23,25,26 However, since these two questionnaires do not include items that explore sexuality and social problems that long-term survivors can experience, a life situation questionnaire was designed to include specific items about sexuality using published data as a guide.32-34 Although not validated, this questionnaire provides additional information to help understand the problems that might prevent long-term survivors from leading a normal life. The participation rate among cases (82%) was similar to that reported in other series.5,6,16,20,27 It was lower (50%) among controls but not much different from that observed in the general Norwegian population or in France (66%).27,35 Global health status was similarly scored as good by cases and controls, which is in agreement with most published data.4,12,18,30,36,37 Rieker et al30 demonstrated that survivors have a better sense of well-being than controls of similar age. Fossa et al36 also reported that 3 years or more after cure, patients express more satisfaction with their lives, feeling stronger and fitter than an age-matched control group. Psychoemotional distress during the treatment quickly decreases in the 2 years following the end of treatment.3,15 In contrast, Douchez et al5 reported significant long-term psychologic problems among survivors of testicular cancer in comparison with French controls. Discrepancies between the results of Douchez et al and those of the present study may relate to the use of a nonvalidated quality-of-life questionnaire and the aggressiveness of treatment. In the Douchez et al study, patients were treated before 1980, when extensive lymph node dissection was used and modern antiemetic drugs were not available. Impairment of sexual life and fertility represent the specific long-term sequelae of testicular cancer survivors.2,38,39 Schover and Von Eschenbach38 found less activity, lower sexual desire, more erectile dysfunction, more difficulty achieving an orgasm, and reduced orgasmic intensity compared with normal controls in up to 25% of 52 long-term survivors. In our series, the incidence of decreased libido, erectile dysfunction, and decreased sexual enjoyment (Table 5) was in agreement with what is generally reported, ranging from 4% to 17%, 6% to 25%, and 6% to 38%, respectively.14,16,38,40 Cases did not report more divorce than controls, a result that confirms what was observed in long-term survivors of Hodgkin’s disease, who even reported less separation than controls.27 In a study conducted by Schover and Von Eschenbach,41 47% of respondents stated the experience of cancer brought them closer as a couple and 28% saw no changes as a result of the cancer. Two other studies42,43 concentrated on the long-term effects of testicular cancer on sexual functioning in married couples and indicated that most couples’ relationships were strengthened after diagnosis and treatment; they became more tightly bonded. Apparently, relationships with friends are not impaired by the disease, with loss of friends reported less frequently by cases than by controls as previously observed among long-term survivors of Hodgkin’s disease.27,44 Although no negative work impact (dismissal, stoppage of work) was observed, cases more frequently reported less professional ambition than controls. Cases seem to have favored their familial life and leisure over their professional life, whereas in other series, better professional performance has been reported among cases cured of testicular cancer as compared with controls.4,18 A major persistent difficulty was the problem of borrowing from banks. This problem seems to be consistent among French long-term survivors independent of the tumor site.27,28,45 In France, the decision to provide a loan is made by the physician of the insurance company related to the bank, and the attitude varies strongly among both physicians and companies. Sometimes, patients must seek loans from many companies before being accepted, generally with a surcharge. An effort should be made to convince medical authorities and insurance companies that cancer-related financial difficulties remain a serious problem for cured patients that is likely to interfere with their familial, social, and professional life as well as their rehabilitation. In cases, the type of therapy administrated did not seem to influence quality of life as evaluated by either questionnaire. In particular, the level of chronic fatigue was not influenced by treatment, in contrast to what has been observed in breast cancer survivors after chemotherapy.46,47 However, in long-term survivors of testicular cancer, a high level of chronic fatigue is linked to low scores on the functional scale and high levels of symptoms (pain, dyspnea, sleep disturbance). Cases with high levels of chronic fatigue also had lower incomes and tended to express more changes in their sex lives (mostly because of impairment of fertility). These observations demonstrate that fatigue is complex and includes social, psychologic, physical, and biologic dimensions that could probably be assessed by specific scales.48,49 Because the questionnaire used only includes a unidimensional measure of fatigue, our results must be considered with caution. No relationship was observed between type of treatment and modification of sexual life, although the problem was reported by 49% of cases, similar to the prevalence reported in other series.33,34 In published series, results are conflicting, except for results for ejaculation dysfunction, which is usually reported as a consequence of lymph node dissection.1,4,7,33,37,50 The frequency and intensity of ejaculation dysfunction depend on the type of lymph node dissection; modern nerve-sparing techniques are likely to reduce the incidence.51 In our study, 23% of patients who had lymph node dissection reported ejaculation problems, a proportion similar to that reported in surgical series of patients with a residual mass after primary chemotherapy.37,52 In our series, impaired fertility was not viewed as a major problem probably because many cases already had children before the disease developed. In young patients, especially those without children, information should be given about the risk of treatment-related sterility and sperm storage should be proposed before chemotherapy.5,16 When used, a testicular prosthesis positively influences general quality of life and sexuality. It is well tolerated and satisfaction is generally high. Nowadays, it should be proposed to any patient undergoing orchidectomy.53 Our results add information about the quality of life of survivors of testicular cancer with a mean follow-up of more than 10 years. They confirm that although health-related quality of life returns to normal, ie, becomes similar of that of a healthy population, some difficulties persist concerning sexual life and borrowing from banks. Systematic information on potential treatment-related sequelae and previous experience of survivors should help new patients to cope with their disease. Medical authorities should also note the difficulties with banks encountered by a substantial proportion of long-term survivors.
We thank Professor Ian F. Tannock, Princess Margaret Hospital and University of Toronto, Ontario, Canada, for scientific advice and the linguistic revision.
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Bower JE, Ganz PA, Desmond KA, et al: Fatigue in breast cancer survivors: Occurrence, correlates, and impact on quality of life. J Clin Oncol 18: 743-753, 2000 47. Broeckel JA, Jacobsen PB, Horton J, et al: Characteristics and correlates of fatigue after adjuvant chemotherapy for breast cancer. J Clin Oncol 16: 1689-1696, 1998[Abstract] 48. Smets EMA, Garsson B, Bonke B, et al: The Multidimensional Fatigue Inventory (MFI): Psychometric qualities of an instrument to assess fatigue. J Psychosom Res 30: 315-325, 1995 49. Loge JH, Kaasa S, Telhaug R, et al: Prevalence and characteristics of fatigue in Hodgkin’s disease survivors. Onkologie 24: 12, 2001 (abstr, suppl 2) 50. Caffo O, Amichetti M: Evaluation of sexual life after orchidectomy followed by radiotherapy for early-stage seminoma of the testis. BJU Int 83: 462-468, 1999[CrossRef][Medline] 51. Turek PJ, Lowther DN, Carroll PR: Fertility issues and their management in men with testis cancer. Urol Clin North Am 25: 517-531, 1998[CrossRef][Medline] 52. Tekgul S, Ozen HA, Celebi I, et al: Postchemotherapeutic surgery for metastatic germ cell tumours: Results of extended primary chemotherapy and limited surgery. Urology 43: 349-354, 1994[CrossRef][Medline] 53. Lynch MJ, Pryor JP: Testicular protheses: The patient’s perception. Br J Urol 70: 420-422, 1992[Medline] Submitted December 18, 2000; accepted August 7, 2001.
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Copyright © 2002 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
18 years at the time of interview; histologically proven testicular cancer (seminomatous or nonseminomatous germ cell tumor [NSGCT]) with diagnosis between 1978 and 1993; alive in complete remission as of January 1998 and free of disease since January 1, 1993; and no history of second malignancy. Of the 120 selected cases, 10 were lost to follow-up, three had relapsed, and one had developed a second malignancy. The remaining 106 cases were enrolled onto the study. 
1,300 US dollars (equivalent to 10,000 French Francs or 1,525 Euros, the level corresponding to the median monthly family income in Calvados). Fifteen percent of cases and 19% of controls had a previous medical history (P = .7), including psychiatric disease in three individuals (one of 11 and two of 22, respectively) and neurologic disease in two (one in each group). Overall, 34 cases had an NSGCT and 36 had a seminoma. For the remaining patient, the histologic type was unknown. The distribution of demographic characteristics (family and social status, income) and follow-up since diagnosis of testicular cancer were similar in the two histologic groups, even after correction for age at interview. The clinical characteristics of cases and the treatments used are listed in 
