Health-related quality of life in men with localized prostate cancer

Authors


Shunichi Namiki md, Department of Urology, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aoba-ku, Sendai 980-8574, Japan. Email: namikin@uro.med.tohoku.ac.jp

Abstract

With the established effectiveness of diverse treatments for localized prostate cancer, the identification of the physical and psychological consequences of the disease and its various treatments has become critical. In the present review, we aim to familiarize the reader with the methodologies of health-related quality of life (HRQOL) research and to review the recent literature on HRQOL outcomes in patients with localized prostate cancer. Studies have shown that prostate cancer and its treatment affect both disease-specific HRQOL (i.e. urinary, sexual, and bowel function) as well as general HRQOL (i.e. energy/vitality and performance in physical and social roles). However, these effects appear to differ according to the type of treatment, stage of disease, age of the subjects, time after treatment, and, more importantly, race or ethnicity. By including HRQOL in clinical decision-making, we can help our patients make more informed treatment choices for localized prostate cancer.

Introduction

Relative to other solid tumors, localized prostate cancer is characterized by an exceptionally protracted natural history. Prostate cancer incidence varies tremendously across the world, depending on ethnic and population generic factors, dietary and other environmental influences, and prostate-specific antigen (PSA) screening and diagnostic practices.1 For the early stage, low risk patients, surgery and radiotherapy can equally provide excellent long-term survival.2 Men diagnosed with localized prostate cancer are typically expected to live for many years with the sequelae of treatment; side-effects may cause significant dysfunction, distress, or disturbance in life's overall quality. The optimal therapy remains undefined so the treatment-associated morbidity is an important determinant in a patient's choice to undergo treatment. Under these circumstances, health-related quality of life (HRQOL) outcome in patients who have undergone each of the aforementioned treatments has become the main point of concern for patients as well as physicians. HRQOL encompasses a wide range of experience, including everyday events, such as intrapersonal and interpersonal responses to illness, and activities associated with professional fulfillment and personal happiness. HRQOL also includes the overall sense of satisfaction that an individual experiences with life and, most importantly, the patient's perceptions of personal health and ability to function. The concept of HRQOL includes not only the symptoms of a given disease or treatment and their impact on the functional status, but also the degree of the associated bother, which is typically defined as the degree of distress associated with the functional limitations or symptoms.3,4

The present review is aimed at familiarizing the reader with the literature on HRQOL in localized prostate cancer. We have briefly summarized the methodology used in quality of life research, and discuss the impact of localized prostate cancer and its treatment on men's HRQOL. The information provided in the present review can be helpful when counseling patients regarding the available treatment choices for localized prostate cancer.

Methodology of HRQOL research in men with localized prostate cancer

Health-related quality of life is a patient-centered variable and is measured by administering questionnaires directly to patients or conducting surveys (also referred to as ‘instruments’ or ‘tools’) in a standardized manner. HRQOL instruments typically contain questions or items that are organized into scales. Each scale measures a different aspect or domain. Before using new HRQOL instruments for clinical purposes, clinicians must ensure validity and reliability of these instruments by arduous pilot testing and statistical analyses according to the principles of psychometric test theory.5 The use of unvalidated questionnaires may result in inaccurate findings and lead to unfounded conclusions. Therefore, it is usually preferable to use the existing validated instruments when assessing HRQOL in prostate cancer rather than attempting to create new tools. A selected list of available instruments is provided in Table 1.

Table 1.  Validated instruments for assessing for prostate cancer health-related quality of life (HRQOL)
InstrumentsAuthors
Generic HRQOL instruments 
 Medical Outcomes Study Short Form 36 (SF-36)Ware et al.6
 Profiles of Moods States (POMS)Lim et al.7
Cancer-specific HRQOL instruments 
 Function Assessment of Cancer Therapy (FACT-G)Cella et al.8
 European Organization for Research and Treatment of CancerDa Silvia et al.9
 Quality of Life Questionnaire (EORTC-QLQ-30) 
Prostate cancer-specific HRQOL instruments 
 Prostate Cancer Index (UCLA-PCI)Litwin et al.10
 Expanded Prostate Cancer Index: Composite (EPIC)Wei et al.11
 Functional Assessment of Cancer Therapy Prostate Module (FACT-P)Esper et al.12
 Prostate Cancer Outcomes Study Questionnaire (PCOS)Stanford et al.13

Generic and cancer-specific HRQOL instruments used in prostate cancer studies

Health-related quality of life of men with prostate cancer is composed of three components or levels: (i) generic health function; (ii) cancer-specific HRQOL; and (iii) prostate cancer-specific HRQOL. The relative contribution of each of these components to the overall HRQOL will depend on the acuity of disease, current treatment, and disease status. Currently, several validated HRQOL instruments are deemed appropriate for each of these components. Since complications such as sexual, urinary and bowel dysfunction are known to be associated with all forms of therapy for localized disease, patients and clinicians must seriously consider HRQOL when selecting a primary therapy for localized prostate cancer. HRQOL is a patient-centered variable that is measured by using questionnaires or surveys that are administered directly to patients in a standardized manner.

Many researchers consider the Medical Outcomes Study 36-Item Short Form (SF-36) as the ‘gold standard’ for measuring general HRQOL. The eight domains of the SF-36 address the health concepts of physical function, social function, bodily pain, emotional well-being, energy/fatigue, general health perceptions, role limitations due to physical problems and role limitations due to emotional problems.6 Several HRQOL instruments have been developed to assess the domains of significance to all patients with cancer, regardless of the site of the malignancy. The European Organization for Research and Treatment of Cancer (EORTC) Quality of life Core Questionnaire (QLQ-C30) is a 30-item survey that incorporates five function scales (physical, role, emotional, cognitive and social), one global health scale, three symptom scales concerning dyspnea, insomnia, appetite loss, consumption and diarrhea) and one scale addressing the financial difficulties due to disease.9 Another cancer-specific HRQOL is the Functional Assessment of Cancer Therapy-General (FACT-G).8 Each item of the FACT-G contains a statement to which the patient has to give a yes/no responses across a five-point range scale. The FACT-G has four domains – physical, social-family, emotional and functional well-being. All of the aforementioned questionnaires were translated into Japanese and used for the evaluation of HRQOL.

Prostate cancer-specific HRQOL instruments

The following HRQOL instruments most commonly used for prostate cancer patients are: (i) the EORTC Quality of Life Questionnaire with a prostate cancer-specific module (EORTC-P);9 (ii) the Functional Assessment of Cancer Therapy-Prostate (FACT-P);12 (iii) the University of California, Los Angeles Prostate Cancer Index (UCLA-PCI);10 and (iv) Expanded Prostate Cancer Index Composite (EPIC).11 UCLA-PCI and EPIC differ from EORTC-P and FACT-P in providing distinct, domain-specific summary scores for urinary, bowel, sexual, and hormonal symptoms. The UCLA-PCI was developed by Litwin et al. in 1998 to evaluate the HRQOL of men who underwent surgery or radiotherapy for localized prostate cancer. The 20 prostate-specific items address six domains – urinary function and bother, sexual function and bother, and bowel function and bother. The fact that the UCLA-PCI generates separate scores to quantify the degree of symptoms (function) and the perception of problems due to symptoms (bother) is important because the bother experienced by patients may not necessarily correlate highly with the level of dysfunction. The Japanese version demonstrated good psychometric properties (reliability and validity) and it was easy to answer and easily understandable by patients and physicians.14 Accordingly, the Japanese version of UCLA-PCI has been incorporated in many outcome studies of Japanese patients. The EPIC instrument (50 items) was constructed by modifying the UCLA-PCI: items regarding irritative, obstructive urinary symptoms and irritative bowel symptoms, and symptoms intimately related to androgen deprivation therapy (ADT) were added. Recently, a Japanese version of the EPIC has been available,15 and Namiki et al. evaluated the correspondence between UCLA-PCI and EPIC using the linking analysis method.16 In the present study the urinary and sexual domains of the UCLA-PCI and EPIC exhibited strong correlations. However, the correlation for the bowel domain was relatively weak. Once investigators select a survey, they will usually continue to use the same survey to achieve consistent comparisons. While it would be ideal for the researchers to agree on using the same surveys, this study may be useful for covering one survey score into another as different surveys are being used across various studies.

In most health survey studies, the patients have to complete a self-report. The data of a number of studies have suggested that a patient's self-reported symptoms are likely to differ from those recorded by his physician.17 The typical mode of survey administration is via a mailed document, although the use of telephone interviews often results in greater survey completion.

Longitudinal studies of HRQOL in prostate cancer allow clinicians and patients to understand the impact of treatment on HRQOL with time. Such studies also account for the underlying differences in HRQOL between patients before treatment, which can generate bias in cross-sectional studies. Understanding the pattern of change in HRQOL after treatment for localized disease is important to patients choosing a primary therapy and also helps in setting reasonable expectations about the treatment outcome. These longitudinal studies allow patients and clinicians to make reasonable comparisons of various treatments and can greatly aid the process of informed decision-making.

HRQOL in localized prostate cancer

Impact of radical prostatectomy

Radical prostatectomy (RP) is a standard treatment for patients with localized prostate cancer and can result in a life expectancy of more than 10 years for those who accept the risk of treatment-related complications.18 Urinary incontinence and erectile dysfunction represent the principal sources of postoperative adverse events for patients who have undergone RP even with nerve-sparing techniques. Longitudinal studies have revealed that immediately after RP, the scores of some physical function domains were lower than the baseline scores. However, these domains recovered to the baseline scores 6 months postoperatively. Mental health, classified as the emotional well-being domain of SF-36, revealed that some postoperative groups had higher scores than the preoperative group. The finding of previous studies revealed that patients experienced a sense of relief accompanying the perceived cure and their tension level was reduced after surgery, which was in turn correlated with a reduction in the feelings of confusion, depression and anger.19

Urinary incontinence is cited as a significant drawback of RP, and although the definition of continence is inconsistent across studies, urinary function and bother are often used as measures of HRQOL in study populations.20 Nevertheless, the finding that incontinence causes significant decreases in HRQOL has been consistently reported in several reports.21 Researchers have reported that significant differences exist in the QOL of men who wear one pad a day for the control of leakage and men who do not wear any protection.22 According to UCLA-PCI scores, which represent disease-specific HRQOL, the urinary function domain, which reflects leakage, substantially declined at 3 months and continued to recover at 6, 12, 18, and 24 months after RP. However, the scores at 24 months after RP were still lower than those at the baseline. Urinary bother had a significantly lower score at 3 months than that at the baseline. At 6 months postoperatively, however, it returned to the baseline levels. When continence was defined as ‘leaked urine not at all’, only 46% of the patients were continent at 24 months after RP. On the other hand, when continence was defined as ‘no pads’, overall 50.5%, 84.4%, 87.6%, 88.5% and 90.5% of men were continent at the 3, 6, 12, 18 and 24-months of follow up points, respectively. Hoffman and colleagues reported that 75% of patients who developed daily urinary continence still reported that the poor function was at most only a small problem.23 The recovery of younger men tended to show more rapid recovery than older men after RP.24 According to the literature on RP, however, about 1–3% of RP-treated patients need surgical correction for post-RP incontinence. A recent survey in Japan confirmed that a large number of men suffer from moderate to severe stress urinary incontinence, and in the majority of cases, the incontinence developed after RP.25 The Japanese urological community needs to provide appropriate treatment for these patients. We recently conducted a cross-cultural comparison of urinary outcome and found that, in addition to age, baseline urinary function and comorbidity were independent predictors of post-RP urinary function.26

Erectile dysfunction (ED) represents the principal source of postoperative adverse events for patients who have undergone RP. In the subsequent year after undergoing RP, patients appeared to experience improvements in sexual functioning. Catalona et al. reported excellent results, with the overall postoperative potency rates of 68% and postoperative continence rates of 92%.27 However, these rates were affected by age, preoperative sexual function, and whether nerve-sparing surgery was carried out.28 The Japanese data on sexual function revealed that the score was substantially lower just after RP at that level thereafter. At 60 months after RP, the sexual function of only 34% of subjects had fully returned to the baseline level. The mean recovery time of the subjects whose sexual function returned to their own baseline level was 13.2 months. Bilateral nerve sparing (BNS) contributed to the recovery of urinary function as well as sexual function after RP.24

Most men who underwent RP were between 50 and 70 years of age. It has been reported that 44% of men with localized prostate cancer who present for RP have moderate to severe lower urinary tract symptoms (LUTS) that may be due to benign prostatic enlargement (BPE).29 Thus, the time course after RP may be indicative of the natural history of LUTS in the absence of the prostate. Accordingly, similar to the evaluation urinary incontinence, it is also important to evaluate the function of the lower tract after RP. A prospective, consecutive study, which evaluated the impact of RP on LUTS revealed that the mean total international prostate symptom score (IPSS) and IPSS QOL scores improved significantly after RP. Especially in men with moderate or severe urinary symptoms, the total IPSS was significantly improved after RP, as reported in another study.30 Interestingly, those who underwent RP rarely experienced spontaneous acute urinary retention, suggesting that RP prevents the progression of LUTS. This is an important advantage of RP, especially in men with moderate to severe LUTS or enlarged prostate who are at a high risk of developing acute urinary retention.31 The beneficial effects of RP had a greater impact than the negative effects of stress urinary incontinence on LUTS. This improvement in the IPSS, however, was noted in men with moderate to severe symptoms rather than on men with no or mild symptoms. Therefore, LUTS in men selected for RP may be attributable to the underlying BPE rather than prostate cancer.

Laparoscopic radical prostatectomy (LRP), which is a minimally invasive procedure as compared with open RP, has been developed as an alternative approach to open RP.32 A multi-institutional longitudinal study conducted in Japan revealed that the patients who underwent LRP reported delayed recovery of urinary and sexual function, which appeared to affect their general HRQOL.33 When carried out by an experienced surgeon, however, the two approaches appeared to be equivalent in terms of HRQOL. LRP still appears to be an evolving procedure.

Nerve-sparing RP procedures appear to preserve erectile function in certain men. In men with low-volume and low-stage disease, nerve sparing does not compromise surgical margins; however, this technique might not be appropriate in men with high-grade tumors or with palpable disease extending toward neurovascular bundles. In the setting of unfavorable clinical features, some men might require resection of both cavernous nerves in order to achieve optimal cancer control. Nerve grafting was initially conceptualized in plastic surgery; since then, its utility has been well established and it has been used for several decades. In 1999, Kim et al. reported a small series of patients with locally advanced prostate cancer who were treated by bilateral non-nerve-sparing RP with bilateral cavernous nerve reconstruction and sural nerve grafting (SNG).34 The vast majority of published studies on nerve grafting have focused on unilateral SNG. The initial data from Baylor College of Medicine,35 MD Anderson Cancer Center,36 and Memorial Sloan-Kettering Cancer Center37 revealed that men who underwent unilateral SNG/contralateral nerve sparing had significantly better potency outcomes and a faster return to potency than men who underwent unilateral nerve sparing alone. Scardino reported that, with nerve grafting for the side of the neurovascular bundle resection, the erectile function of the patients who underwent unilateral nerve-sparing recovered to approximately the same level of those who underwent bilateral nerve-sparing.38 A large-scale study from Japan with a 3-year follow-up period used the UCLA-PCI measurement.39 Bilateral nerve sparing, unilateral nerve sparing/SNG, and unilateral nerve sparing alone were all studied. At 24 months, both the bilateral nerve sparing group and the unilateral nerve sparing plus SNG group showed similar results. Additional contemporary studies have independently corroborated and supported the benefits of unilateral nerve grafting on potency.40–42 However, as stated, it remains unclear whether the potency outcomes with unilateral SNG are secondary to the spread nerve or the interposition graft. It is difficult to draw definitive conclusions about the SNG procedure as the men who elect it often constitute a highly selective sample of men. A recent well-designed randomized controlled trial failed to demonstrate significant improvement in potency after unilateral SNG.43 Although the investigators conceded that the compliance with ED therapy after surgery was poor, the results of their trial were disappointing and raised doubts regarding the future use of interposition grafting after unilateral nerve-sparing RP. The actual benefits of unilateral SNG still remain to be determined.

Robotic assisted radical prostatectomy (RARP) is the most commonly used robotic procedure throughout the world. While RARP constituted only 10% of the total of RP procedures carried out by American urologists 2 years ago, it has increased to more than 60% in 2008–2009. Surgeons experienced in open RP have raised a concern about the reduction in early continence after RARP/LRP in comparison with that after open RP.44 Preliminary data indicate that RARP has more advantages than open RP, namely reduced blood loss, decreased pain, early mobilization, shorter hospital stay and lower margin rates.45,46 Most intra-institutional studies demonstrate good postoperative continence and potency with RARP; however, this needs to be viewed in the context of the paucity of randomized data available in the literature.47,48 There are no definitive data to show that RARP is more efficient than standard LRP, but the fact that this technique has reached parity with laparoscopy within 5 years is encouraging.

Impact of external beam radiation therapy

External beam radiation therapy (EBRT) is the second most commonly used treatment modality for localized prostate cancer. Over the years, treatment techniques for EBRT have continued to evolve toward higher therapeutic doses with minimum toxicity.49 It is apparent, however, that transient irritative and obstructive urinary symptoms occur during and in the period immediately after EBRT. Questions about urgency as well as incontinence are relevant to those experiencing urinary problems and for patients whose daily activities were affected. Persistence of bladder and bowel symptoms was also evident with longer follow-up in one cross-sectional study of conformal EBRT.50 Moreover, the manifestation of toxicities in EBRT patients may occur in a delayed fashion, and the use of neoadjuvant and adjuvant ADT is common.51 Thus, one must be conscious of the treatment technique and the duration of follow-up in HRQOL studies of patients undergoing EBRT. With a median follow-up period of >30 months, urinary incontinence, hematuria, stool frequency, stool soilage and other bowel symptoms were also found to be significantly higher in men receiving EBRT than in those on expectant management. Problems such as increased frequency, increased urgency, diarrhea, and bleeding with movements were reported more often by men treated with EBRT than those treated with RP. More immediate effects of EBRT on urinary, sexual, and bowel function and cancer level HRQOL have been well documented.52–56 Japanese men with localized prostate cancer who underwent EBRT appear to have similar general HRQOL to that of men who underwent RP,57 which was similar to other groups.58 Fatigue appeared to be the most common complication in men treated with EBRT. EBRT has been associated with increased fatigue from pretreatment at up to 3 and 12 months of follow up.59 Overall, significant advances in EBRT techniques have improved HRQOL outcomes. Significant effects on disease-specific HRQOL are apparent after EBRT, even with long-term follow up; however, few effects are observed in the case of generic and cancer-specific domains.

In comparison with conventional external beam or conformal radiation therapies, intensity modulated radiation therapy (IMRT) has been shown to improve the local control and disease-free survival in patients with localized prostate cancer.60 Zelefsky et al. reported that IMRT reduced acute and rectal toxicities to a greater extent as compared with conventional radiotherapy techniques.61 We found that HRQOL of Japanese men treated with IMRT was better than that of men treated with conventional or conformal radiotherapy for 2 years after the therapy.62

Impact of brachytherapy

Brachytherapy (BT), which is often presented as a less invasive alternative to RP and EBRT, has been recognized as a standard treatment option for men with low-risk prostate cancer. In Japan, the use of iodine-125 seed source was legally approved in June 2003. Eton et al. analyzed the immediate changes in general HRQOL in 256 men after treatment with BT, RP, and EBRT.63 HRQOL differences were noted in the domains of physical function, social function and bodily pain. In each domain, the patients who underwent BT had higher HRQOL scores than those who underwent RP. On the other hand, mental health improved substantially and showed continued improvement for as long as 12 months after RP, while the patients treated with BT consistently remained stable.

Although BT appeared to have a clear advantage over RP in terms of urinary function (urinary control), transient irritative and obstructive urinary symptoms were reported to occur during and after BT.64 The BT group experienced a significant increase in IPSS and this trend continued for more than 6 months after treatment. These symptoms were relatively apparent in our analysis using IPSS. Thus, the urinary bother curve shows more significant adverse treatment effects. In our experience, the IPSS had more than doubled at 3 months after BT. This sharp increase in urinary symptoms in a short period of time is clinically significant.65 However, the IPSS were indistinguishable from the baseline measures one year after treatment. This study revealed that continence is not a sole determining factor of urinary bother, and BT patients may be ‘dry’ but suffer from urgency, frequency, and dysuria. The potency rates following BT have been encouraging, being as high as 90%, although a decrease occurred from 3 to 6 years later.66 Additional long-term studies with a larger number of patients are necessary to fully understand the impact of each treatment on the HRQOL for Japanese men who undergo BT.

Impact of androgen deprivation therapy

There are a few articles reporting the effects of ADT on HRQOL. Heer and O'Sullivan compared patients receiving ADT and those with asymptomatic advanced cancer.67 They documented better HRQOL among patients who opted to defer treatment as compared with those who opted for early interventions. Potosky et al. studied HRQOL in patients with localized prostate cancer who were treated initially with ADT or not treated reported that protracted ADT was associated with worse physical function and more fatigue as compared with patients receiving no therapy.68 On the other hand, Lubeck et al. stated that patients on ADT did not exhibit any noticeable decrements in the scores of the general HRQOL at one year after therapy.69 With regard to Japanese subjects, almost all HRQOL measures except for sexual function were mostly unaffected by ADT.70 Although there was a substantial decrease in sexual function, the subjects did not complain about sexual bother. Patients receiving ADT felt less bothered by sexual dysfunction presumably because they were well informed of the potential for deterioration of sexual function before treatment and thus had lower expectations about post-treatment sexual function.

Impact of watchful waiting

Relatively few studies have evaluated the HRQOL of men undergoing watchful waiting. The Prostate Cancer Outcomes Study is a population-based study that examined the HRQOL in a subset of men diagnosed with localized prostate cancer in 1994 and 1995.71 As one might expect, men undergoing watchful waiting tended to be older and more frail, with >50% of them aged between 70 and 79 years. Among 661 men who had not received surgery or radiation in the first year after diagnosis, 245 received ADT. The QOL assessed in this study was based on several existing instruments. In a recent randomized controlled trial, urinary obstructive symptoms, such as a weak urinary stream, were significantly more prevalent among men assigned to watchful waiting vs those who underwent RP.72

Impact of cryosurgery

Cryosurgery is increasingly used to treat men with localized prostate cancer or those who have experienced a recurrence episode after radiation therapy. The side-effects of cryosurgery include incontinence, urethral sloughing, perineal pain, and erectile dysfunction.73 However, there are very few studies that have investigated the HRQOL issues related to this treatment modality. Perrotte et al. found that the side-effects of this treatment had a substantial negative effect on HRQOL in both the short and long-terms; however, when urethral warming was carried out during the procedure, some of these side-effects were reduced.74 Robinson and colleagues found that, 3 years after the procedure, 13% of their sample had regained erectile function and an additional 34% were able to have intercourse with the help of erectile aids.75 Anastssiadis et al. compared cryotherapy as a primary therapy with salvage cryotherapy and found that those who received this modality for primary treatment fared significantly better with regard to physical and social functioning. ED was the most significant and severe side-effect, but urinary symptoms were also noted to be important.76 A review of cryosurgery cases revealed that this was an acceptable therapy both as a primary treatment and for those who experienced a recurrence episode after radiation therapy, with a tolerable effect profile and reasonable HRQOL.77

Cross-cultural comparative study

Race and ethnicity are important factors in HRQOL because certain racial groups have predominant preferences for and trust in health systems and these factors are likely to influence HRQOL and patient satisfaction with care.78 Most ethnicity-based comparisons of HRQOL after prostate cancer treatment have been limited to the studies of non-Hispanic whites, African-Americans, and Hispanics in the USA.79 The HRQOL articles are published from 22 countries, with the USA producing the most (47%), followed by the UK (8%), Canada (8%) and Japan (6%).80 Thus, there is insufficient information regarding HRQOL of Japanese men diagnosed with prostate cancer and most HRQOL information came from the experience of well educated white men.

In Japan, increased screening for prostate cancer has lead to an increase in the apparent incidence of prostate cancer, and resulted in a shift to an earlier age and stage at diagnosis, a trend similar to that in the USA and European countries. In the past decade, there have been a growing number of published reports related to HRQOL in Japanese men with prostate cancer. Table 2 presents cross-sectional or longitudinal studies that have assessed and compared the impact of treatment on HRQOL in Japanese men with localized prostate cancer. Japanese men who underwent EBRT appear to have similar general HRQOL to men who have received RP.65,109 Almost all HRQOL measures of Japanese men with prostate cancer except for sexual function were mostly unaffected by ADT.14,15,70,94 Using a self-reported questionnaire, Japanese men reported poor sexual function score not only before but also after treatment.23,95,111

Table 2.  Selected studies comparing health-related quality of life (HRQOL) following treatment for Japanese men with localized prostate cancer
StudyYearDesignQOL methodsNo. patientsTherapyReference
  1. ADT, androgen deprivation therapy; BT, brachytherapy; EBRT, external beam radiation therapy; EPIC, Expanded Prostate Cancer Index: Composite; EORTC-P, European Organization for Research and Treatment of Cancer (prostate cancer module); FACT-P, Functional Assessment of Cancer Therapy Prostate Module; IPSS, international prostate symptom score; RP, radical prostatectomy; SF-36, Medical Outcomes Study Short Form 36; UCLA-PCI, UCLA Prostate Cancer Index.

Akakura K1999LongitudinalEORTC-P46RP, EBRT81
Arai Y2008LongitudinalFACT-P203ADT82
Arai Y1999Comparison groupOriginal questionnaire60RP83
Egawa S2003LongitudinalOriginal questionnaire83RP84
Egawa S2001Cross-sectionalSF-3685EBRT85
Hara I2003Cross-sectionalEORTC-P106RP86
Hashine K2009LongitudinalSF-8, EPIC184RP, BT87
Hashine K2005Cross-sectionalEORTC-P57EBRT88
Inoue S2009LongitudinalSF-36, UCLA-PCI194RP89
Ishihara M2006Comparison groupSF-36, UCLA-PCI141Before treatment90
Jo Y2005LongitudinalSF-36, UCLA-PCI182RP, BT91
Kaiho Y2005LongitudinalUCLA-PCI85RP92
Kakehi Y2002Cross-sectionalUCLA-PCI125RP, EBRT14
Kakehi Y2007Cross-sectionalEPIC460RP, EBRT, ADT, BT15
Kato T2007Comparison groupSF-36, UCLA-PCI56ADT70
Matsubara A2005LongitudinalUCLA-PCI, IPSS41RP93
Mizokami A2007Cross-sectionalAndrogen Deficiency in Aging Males628RP, ADT94
Namiki S2009LongitudinalSF-36, UCLA-PCI, IPSS154RP23
Namiki S2008LongitudinalSF-36, UCLA-PCI, IPSS862RP, EBRT26
Namiki S2008Comparison groupUCLA-PCI874RP, BT65
Namiki S2008LongitudinalUCLA-PCI373RP95
Namiki S2009LongitudinalSF-36, UCLA-PCI827RP, BT96
Namiki S2008LongitudinalSF-36, UCLA-PCI558RP97
Namiki S2007Cross-sectionalUCLA-PCI, EPIC385RP, EBRT, WW16
Namiki S2007LongitudinalUCLA-PCI113RP39
Namiki S2007Cross-sectionalSF-36, UCLA-PCI, IPSS340RP, EBRT98
Namiki S2006LongitudinalSF-36, UCLA-PCI349RP99
Namiki S2006LongitudinalUCLA-PCI, IPSS225RP30
Namiki S2006LongitudinalSF-36, UCLA-PCI144EBRT62
Namiki S2006LongitudinalSF-36, UCLA-PCI, IPSS137RP, EBBT65
Namiki S2005LongitudinalSF-36, UCLA-PCI166RP33
Namiki S2005Cross-sectionalUCLA-PCI198RP100
Namiki S2005LongitudinalSF-36, UCLA-PCI112RP101
Namiki S2005LongitudinalSF-36, UCLA-PCI72RP, ADT102
Namiki S2004Cross-sectionalSF-36, UCLA-PCI264RP, EBRT57
Namiki S2004LongitudinalSF-36, UCLA-PCI72RP103
Okeneya T2007LongitudinalIPSS100BT104
Saito S2006LongitudinalUCLA-PCI80RP105
Sugimoto M2008Cross-sectionalSF-8, EPIC457RP, EBRT, BT, ADT106
Yoshimura K2007LongitudinalSF-36, UCLA-PCI107RT107
Yoshimura K2005Comparison groupSF-36349RP, ADT108
Yoshimura K2004LongitudinalEORTC-P135RP, EBRT109
Yoshimura K2003LongitudinalEORTC-P37RP, ADT110

Namiki et al. carried out a cross-cultural comparative study on the recovery of sexual and urinary function and bother during the first 2 years after RP between American and Japanese men.97 Using a self-reported questionnaire, the Japanese men reported lower sexual function scores at baseline, even after adjusting for age, PSA and comorbidity as compared with those reported by the American men. At two years after RP, the sexual function of 22% of Japanese men and 35% of American men had fully returned to the baseline levels. In addition, American men were more likely than Japanese men to regain their baseline sexual function by 24 months after treatment. Population-based data from Japan indicate that the proportion of ED is 20%, 42% and 64% for men in the age groups of 50–59, 60–69 and 70–79 years, respectively: these values were higher than those reported for men from other countries.112,113 On the other hand, Japanese and American men did not differ in sexual bother scores at baseline. After RP, the Japanese men demonstrated significantly equivalent or better sexual bother scores (less distress) than did the American men at all postoperative time points. While the sexual bother of only 24% and 40% of American men returned to baseline levels at 1 and 6 months postoperatively, 39% and 73% of Japanese men exhibited similar tendencies (Figs 1,2).

Figure 1.

Longitudinal changes in sexual function and bother over time in Japanese and American men who underwent radical prostatectomy. Reprinted with permission from Namiki et al.80inline image, UCLA Sexual Function; inline image, Japan Sexual Function; inline image, UCLA Sexual Bother; inline image, Japan Sexual Bother. *Adjusted for age, baseline prostate-specific antigen and nerve-sparing.

Figure 2.

Kaplan–Meier analysis of the proportion of subjects who underwent radical prostatectomy and whose sexual function (a) and sexual bother (b) scores returned to baseline level over time. Reprinted with permission from Namiki et al.80inline image, Japanese; inline image, American.

Even before treatment, Japanese men with localized prostate cancer were more likely than American men to report poor sexual desire, poor erection ability, poor overall ability to function sexually, poor ability to attain orgasm, poor quality of erections, infrequency of sexual erections, infrequency of morning erections, and less intercourse in the previous 4 weeks. However, Japanese men were less likely than American men to be bothered by their sexual function.95 Even though Japanese beliefs regarding sexuality have recently witnessed a considerable change, Japanese men still hesitate in consulting physicians about their sexual issues. Thus, the deterioration of sexual activity did not appear to impact HRQOL in Japanese men as much as that in American men. This suggests that cultural factors and deeply embedded health beliefs may play a decisive role in defining health-seeking behaviors related to sexual problems. Moreover, while male erectile rigidity contributes to the frequency of sexual intercourse, it is not necessarily associated with a satisfactory sexual life of the partners of Japanese men.114 The discrepancy between the responses of Japanese males and those of their partners might be explained by discordant views concerning what constitutes a satisfactory sexual life (e.g. non-coital intimate activities).

The attitude of Japanese urologists toward their patients' sexual problems may compound the hesitation about discussing sexual issues. The urologists appear less proactive in dealing with ED in cancer patients, and instead tend to focus more on outcomes such as laboratory test results. This is consistent with findings of a previous study that used a nationwide survey in Japan on the attitudes of breast cancer surgeons: one-third of doctors addressed the sexual concerns of their patients after surgery as about ‘nothing in particular’.115 Physical conditions in Japanese hospitals often limit confidentiality, perhaps decreasing motivation to discuss such sensitive issues. American urologists tend to prescribe therapy for their patients with post-prostatectomy ED, in part because of the belief that early sexual rehabilitation may promote post-surgical recovery of erectile function.116

The use of phosphodiesterase-5 (PDE-5) inhibitors (such as sildenafil, tadalafil, and vardenafil) has been widely publicized as the solution for ED after prostate cancer treatment. Although PDE-5 inhibitors have been available since 1999 in Japan, it is striking that the Japanese men are much less likely to use PDE-5 inhibitors than the American men.95,117 However, the Japanese men who used PDE-5 inhibitors reported better sexual function than those who did not after RP as well as before RP. In contrast to Japanese men, American men who took PDE-5 inhibitors after RP reported lower sexual function than those who did not.118 This finding mirrors the differences between Japanese and American men with regard to their motivations for sexuality. Conversely, American men are more proactive than Japanese men in seeking care for ED after prostate cancer treatment.119 Most Japanese men might not take any action; while American men may seek support from their partners, family members or other sources of social support.

With regard to urinary HRQOL, there were no differences in urinary function or bother at baseline between Japanese men and American men. Japanese men reported a lower incidence of urinary dysfunction (urinary incontinence) and felt less distress than American men at 1 month after RP. For RP patients, urinary function and bother scores decreased from baseline to a nadir at 1 month after surgery and then continued to increase through 12 months after RP. The mean scores at 1 month differed significantly between the men of both countries. Multivariate analyses revealed a non-linear pattern of recovery and a significant difference in this pattern between the men of both countries with regard to urinary function (control) and bother after RP.26 (Fig. 3) If Japanese men had historically not been screened as often, they would be expected to have presented with worse disease, making them more like African-American men who reported worse outcomes.120 In this analysis, however, we obtained an opposite result: Japanese men presented with worse disease but reported better outcomes than the American men. It is not clear whether the national variations we found in early urinary function recovery were attributable to intrinsic differences or the relative disease severity in our two samples. The two cultures may simply have different concepts of health, well-being, and illness or disease with regard to urination.

Figure 3.

Longitudinal changes in urinary function and bother over time in Japanese and American men who underwent radical prostatectomy. Reprinted with permission from Namiki et al.25 (a) Urinary function (UF). (b) Urinary bother (UB). inline image, USA; inline image, Japan. RP, radical prostatectomy.

Future perspectives

There is insufficient information regarding HRQOL of Asian men including Japanese men diagnosed with prostate cancer. In the absence of a biological explanation for the cross-national differences, however, we suspect that the cultural differences in how the HRQOL surveys were interpreted may explain the differences in Japanese and American men with prostate cancer. Different cultures have different concepts of health, well-being, illness, and health insurance systems. A concept that is well developed in one country may not even exist in another one. Even if we use HRQOL studies with validated survey instruments in English, we need to be aware that these multicultural issues may introduce a significant bias in the collection of data and reflect not the men's preferences but the medical care they received.

Conclusions

Health-related quality of life assessment for prostate cancer is a rapidly evolving field. The diagnosis of prostate cancer, prostate cancer therapies, disease progression, and disease recurrence have all been shown to have significant and measurable effects on a patient's HRQOL. Given that prostate cancer is one of the most commonly observed solid tumors, it is important to focus on the treatment modalities of this cancer and how its various treatments have unique effects on the quantity and quality of life. Further, while men with prostate cancer are being diagnosed at a younger age and are observed to live long durations with the disease, it is critical that we obtain a better understanding of all the facts that could influence the short-term and long-term functional states and HRQOL in prostate cancer patients.

Radical prostatectomy, external beam radiation therapy, brachytherapy and androgen deprivation therapy all affect the urinary, bowel and sexual domains of HRQOL. Although surgery is associated with higher rates of sexual dysfunction than radiotherapy, patients appear to experience similar amounts of bother from sexual dysfunction regardless of the type of primary treatment. This finding illustrates that the perception of the post-treatment sexual dysfunction is highly personal and varies among individuals. Patients undergoing surgery were found to experience significant urinary dysfunction due to stress urinary incontinence, while those receiving EBRT or BT experienced urinary dysfunction as well, although it is usually in the form of irritative voiding symptoms. Importantly, these irritative symptoms can cause as much if not more bother than stress incontinence after surgery. Furthermore, EBRT and BT can have a significant effect on bowel function, which is not noted in the surgical group.

Race and ethnicity are important factors that affect HRQOL because the patient's preferences for and trust in health systems that are predominant in certain racial groups are likely to influence HRQOL and patient satisfaction with care.

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