Quality of life after radical prostatectomy in Japanese men: A 5-Year follow up study

Authors


Shunichi Namiki md phd, 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

Objectives:  To measure health-related quality of life (HRQOL) after radical prostatectomy (RP) in Japanese men with localized prostate cancer.

Methods:  A total of 154 patients who underwent RP were included in this 5-year longitudinal survey. The Short Form 36-Item Health Survey, the University of California, Los Angeles, Prostate Cancer Index and the International Prostate Symptom Score questionnaires were administered at diagnosis and nine times afterwards.

Results:  Patients undergoing RP showed problems in some physical domains of general HRQOL, but these problems diminished over time. Mental health and social functions significantly improved during the follow-up period. The urinary function substantially declined at 3 months and continued to recover gradually but never returned to baseline. Most patients (95%) recovered to their baseline urinary bother score within 60 months. The overall mean total International Prostate Symptom Score progressively improved with time. On the other hand, at 60 months after RP, only 34% of subjects had fully returned to baseline sexual function. By 5 years postoperatively, 78% of the men had reached baseline sexual bother and the mean recovery time was 8.6 months. Adverse effects of RP on sexual function and bother were mitigated by bilateral nerve-sparing procedures up to 5 years after the operation.

Conclusions:  Despite reported problems with sexuality and urinary continence, general HRQOL was mostly unaffected by RP after 6 months in our survey with functional outcomes remaining relatively stable in the majority of patients.

Introduction

Currently, the most common therapeutic options for localized prostate cancer are radical prostatectomy (RP), external radiation, and interstitial brachytherapy. RP is considered an especially safe and effective treatment for localized prostate cancer and has gained popularity among Japanese urologists over the last decade.1 As prostate cancer is increasingly diagnosed at early stages and therefore with more favorable survival outcomes, the basis on which patients select primary therapy has shifted toward considerations of health-related quality of life (HRQOL).2,3 Accordingly, HRQOL assessment has become an important form of outcome-based research that may weigh heavily on the justification of health care expenditures and the treatment selection by patients.

Several assessments of HRQOL after prostate cancer treatment have been limited to studies of non-Hispanic whites, African-Americans, and Hispanics in the USA.4,5 Previously, we detailed HRQOL recovery in Japanese men with localized prostate cancer followed for 2 years after RP.6 In the current analysis we assessed temporal changes in HRQOL up to 5 years following RP using validated questionnaires. To our knowledge the current study is the longest-term prospective study to assess the impact of RP on general and disease-specific outcomes following RP in Japanese men with clinically localized prostate cancer.

Methods

Patient population and data collection

Between June 2001 and December 2002, a total of 154 patients with newly diagnosed localized prostate cancer (T1-T3N0M0) were treated with radical prostatectomy at Tohoku University Hospital and its affiliated hospital. The RP was performed using essentially the same technique as originally described by Walsh;7 all procedures were carried out by staff urologists in each institute. The indications for a nerve-sparing procedure depended on preoperative factors such as the needle biopsy pathology parameters of Gleason score, average percent of biopsy core involved with tumor and percent of side-specific cores with tumor, along with the clinical parameters of serum prostate-specific antigen and digital rectal examination.8 Intraoperative factors were also considered, prioritizing cancer control.

All recruitment and research protocols were approved by the Ethics Committee, Tohoku University School of Medicine. All patients were informed of their cancer diagnosis before being asked to fill out the HRQOL questionnaires. Those who agreed to participate in this study received from their urologist a questionnaire, an informed consent form, and a prepaid envelope for returning the questionnaire. The baseline interview was conducted after the diagnosis. Follow-up assessments were completed 3, 6, 12, 18, 24, 36, 48 and 60 months after RP.

HRQOL methodology and statistical analysis

We evaluated general HRQOL with the Short Form 36-Item Health Survey (SF-36).9,10 The general scales cover eight domains, four physical and four emotional. The prostate specific HRQOL was assessed with the University of California, Los Angeles Prostate Cancer Index (UCLA PCI)11 and International Prostate Symptom Score (IPSS).12 UCLA PCI encompasses urinary, bowel, and sexual problems and the extent of bother from problems in each area. SF-36 and UCLA PCI quality of life scores for the various domains are shown as mean plus or minus one standard deviation (SD) in scales of 0 to 100, with a higher score always representing better HRQOL. Both questionnaires have already been translated into Japanese and the validity and reliability have been tested previously.13,14 The IPSS measures obstructive and irritative urinary symptoms and is scored from 0 to 35, with a higher score indicating worse symptoms.

Statistical analysis

The analysis focused on comparing each HRQOL score of the postoperative groups with the baseline scores. Statistical analysis made P < 0.05 significance using the Mann–Whitney U-test. Next, we assessed urinary function and bother, sexual function and bother, and IPSS using the principles of survival analysis with Cox proportional hazard models to characterize recovery trends. We created models based on the occurrence of each subject's return to his own baseline score. A subject was considered to have returned to baseline if his domain score was at least 90% of his baseline. Once a subject returned to baseline, his time to return was censored.

Results

Background characteristics of the study group

Of the 154 subjects, two subjects who died during the 5-year follow up and three subjects who showed clinical recurrence were excluded. There were no treatment-related deaths. Only patients with preoperative HRQOL data and data from at least two later times (3, 6, 12, 18, 24, 36, 48 or 60 months after surgery) were included in the analysis, resulting in a final study cohort of 143 subjects.

Table 1 lists the selected demographic and clinical characteristics of the study sample. The majority of subjects were older than 65 years (64%). At the time of the baseline survey, 94% of the men were married or lived with a partner and 52% were employed. The respondents showed a median preoperative prostate-specific antigen (PSA) of 11.2 ng/mL (range 3.3–54.0). Histopathologically organ-confined disease was found in 79% (n = 113) of the surgical specimens. Most patients (69%) experienced comorbidities, the most common of which were hypertension (29%), diabetes (20%), gastrointestinal (18%), cardiovascular (12%) disease and other kinds of carcinoma (7%), but these comorbidities were well controlled. Of the 143 subjects, 55 (38%) patients did not undergo nerve preservation, and 88 (62%) patients underwent either unilateral (63 [72%] patients) or bilateral (25 [28%] patients) nerve-sparing surgery. Twenty-four (17%) subjects received salvage therapy during the study period. In detail, nine men underwent radiotherapy, ten men received hormonal therapy, and five men received both radio and hormonal therapy.

Table 1.  Demographic and clinical characteristics of study population
No. patients143%
  1. LH-RH, luteinizing hormone-releasing hormone; PSA, prostate-specific antigen; SD, standard deviation.

Age  
 Mean (SD)65.8 (5.6) 
 <655136
 65+9264
PSA at diagnosis (ng/ml)  
 Mean (SD)11.2 (9.2) 
 <109365
 10+5035
Pretreatment tumor stage  
 T15538
 T26243
 T32618
Pathological tumor stage  
 T211379
 T33021
Gleason score  
 <76344
 7+8056
Nerve-sparing procedure  
 Bilateral3524
 Unilateral5337
 None5539
Salvage therapy  
 None11983
 Radiation therapy96
 LH-RH analog21
 Antiandrogen86
 LH-RH analog plus antiandrogen21
 Radiation therapy plus hormonal therapy32
Comorbidity count  
 04431
 15539
 23524
 3 or more96
Working status  
 Full-time worker5539
 Part-time worker1913
 Retired/no job6948
Marital or relationship status  
 Married or living with spouse or partner13594
 Unmarried or not in significant relationship86

General HRQOL assessment

The questionnaire submission rates among these patients were 95%, 97%, 100%, 91%, 99%, 100%, 91% and 87% at 3, 6, 12, 18, 24, 36, 48 and 60 months after treatment, respectively. The mean HRQOL scores are shown in Figure 1 (general scales). Of the eight SF-36 domains, role limitations due to physical problems and bodily pain significantly decreased at 3 months (P = 0.002 and P = 0.033, respectively), but at 6 months these domains recovered to the baseline. Social functioning scores were statistically higher than baseline after two years postoperatively. Mental health scores were statistically higher throughout the postoperative period (P < 0.05). Other domains including physical functioning, vitality, role limitations due to emotional problems, and general health perception showed no significant difference between baseline and any of the observation periods. There were no significant differences in any of the general HRQOL domains between the subjects who received postoperative salvage therapy and those who underwent RP alone (data not shown).

Figure 1.

Longitudinal changes in general health-related quality of life over time following radical prostatectomy. Domains in the Short Form 36-Item Health Survey. (a) PF, physical function; RP, physical role; BP, bodily pain; GH, general health perception; (b) VT, vitality; SF, social function; RE, emotional role; MH, mental health.

Disease specific HRQOL assessment

According to UCLA PCI scores, the urinary function, which reflects urinary control, substantially declined at 3 months and continued to recovery after 6 months but still scored lower than the baseline (P < 0.01). Urinary bother had a significantly worse score at 3 months than that at baseline (P = 0.03). At 6 months after surgery, however, it returned to the baseline (Fig. 2). No significant differences were observed with regard to bowel function or bother between the baseline and any of the postoperative time groups (Fig. 3). The data of sexual function showed a substantially lower score just after RP and remained at a deteriorated level (Fig. 4). Similarly, sexual bother scored significantly lower at each postoperative time point in a parallel way. According to Fig. 5, the mean total IPSS score showed statistically significant improvement after 6 months following RP (P < 0.05). Furthermore, a statistically significant decrease was observed in mean IPSS in the subjects presenting with moderate/severe lower urinary tract symptoms (LUTS) (IPSS 8 or greater) (data not shown). Figure 6 shows Kaplan–Meier curves representing a return to baseline HRQOL score. The recovery of urinary function to baseline was 35%, 56%, 68% and 78% at 3, 6, 12 and 24, months after RP, respectively. There was little additional recovery after 24 months. At 60 months, 5% of patients reported being bothered by urinary incontinence after RP. Mean recovery for urinary function and bother was 9.3 and 6.1 months, respectively.

Figure 2.

Longitudinal changes in urinary health-related quality of life over time following radical prostatectomy. UF, urinary function; UB, urinary bother. Asterisks indicate statistically significant differences between baseline and each time point (P < 0.05).

Figure 3.

Longitudinal changes in bowel HRQOL over time following radical prostatectomy. BF, bowel function; BB, bowel bother. Asterisks indicate statistically significant differences between baseline and each time point (P < 0.05).

Figure 4.

Longitudinal changes in sexual HRQOL over time following radical prostatectomy. SXF, sexual function; SXB, sexual bother. Asterisks indicate statistically significant differences between baseline and each time point (P < 0.05).

Figure 5.

Longitudinal changes in IPSS over time following radical prostatectomy. Asterisks indicate statistically significant differences between baseline and each time point (P < 0.05).

Figure 6.

Kaplan–Meier analysis of the proportion of subjects returning to baseline score over time. (a) Urinary function, (b) Urinary bother, (c) Sexual function, and (d) Sexual bother.

On the other hand, at 60 months after RP, only 34% of subjects had fully returned to baseline sexual function. Among those who did return to their own baseline, the mean recovery time was 13.2 months. The bilateral nerve-sparing (BNS) procedure made a significant contribution to the recovery of not only sexual function and bother but also urinary function compared with the non-nerve-sparing procedure (P = 0.042 and P = 0.037, respectively). There were no significant differences among the nerve-sparing groups with regard to the urinary bother domain (Fig. 7). By 5 years postoperatively, 78% of the Japanese men had reached baseline sexual bother and the mean recovery time was 8.6 months. Changes in the patient's sexual quality of life were reflected in their age at diagnosis. Younger men (younger than 60) tended to show more rapid recovery of sexual function (P = 0.030) than older men (70 years or older) as well as urinary function (P = 0.014) (Fig. 8a,c). In contrast, older subjects were somewhat more likely than younger subjects to return to their baseline sexual bother score (P = 0.005) (Fig. 8d).

Figure 7.

Kaplan–Meier analysis of the proportion of subjects returning to baseline score stratified by age over time. (a) Urinary function, (b) Urinary bother, (c) Sexual function, and (d) Sexual bother. BNS, bilateral nerve-sparing; UNS: unilateral nerve-sparing; NNS, non-nerve-sparing

Figure 8.

Kaplan–Meier analysis of the proportion of subjects returning to baseline score stratified by the nerve-sparing procedure over time. (a) Urinary function, (b) Urinary bother, (c) Sexual function, and (d) Sexual bother.

Discussion

The current study has several important findings. First, in several domains of the SF-36, those who underwent RP had significant declines in physical domains such as role limitations due to physical problems and bodily pain, but had significant improvements in these scores up to 6 months, with values almost returning to the pretreatment levels. This is consistent with findings from other investigators, who have shown that men with localized prostate disease treated via RP claim problems in some domains of general HRQOL, but these problems diminish over time.15,16 Furthermore, mental health and social functioning, classified as the mental domain of the SF-36, revealed that some postoperative groups had higher scores postoperatively than they had had preoperatively. Previous studies found that, following surgery, with the relief accompanying the perceived cure, the tension level was reduced and that a reduction in tension was correlated with a reduction in feelings of confusion, depression and anger.17

Second, recovery of urinary function occurred in greater than 80% of our subjects at 60 months following RP. Urinary incontinence is a concern particularly relevant to men undergoing RP because surgery more frequently negatively affects continence than other treatment modalities, and because patients rate urinary status as one of their greatest concerns regarding HRQOL. On the basis of our findings, improvements in urinary control that have previously been observed in the first 2 years of post-RP recovery appear not to extend substantially thereafter, which was similar to previous other studies.18 In line with our results, Hoffman and colleagues showed that 75% of those who developed daily urinary incontinence still reported that the poor function was at most only a small problem.19 Consequently, the recovery from urinary bother was observed early at 6 months and in the remaining postoperative periods, showing that postoperative incontinence was, if any, minimal in the majority of the patients and their problems were not so severe.

The impact of the nerve-sparing procedure on urinary continence is controversial. We have already reported that the recovery profile of continence was significantly associated with the BNS group confirmed by objective electrophysiological classification showing better recovery of continence in the early postoperative phase.20,21 Indeed, this was evident in our long follow-up study. Moreover, our study revealed that younger men were more likely to return to baseline urinary function. This was consistent with several studies that have shown an inverse relationship between age and postoperative urinary function using validated HRQOL instruments.22,23

Third, the effect of RP on LUTS was ascertained for the entire group of men. Previously, we assessed a 2-year, prospective, consecutive series in which we examined the impact of RP on LUTS.24 In the current study, IPSS remained relatively stable even after 2 years. This finding is consistent with other reports in which RP appears to not only significantly improve LUTS in men with clinically significant baseline symptoms, but also prevent the progression of LUTS in the majority of men presenting with or without clinically significant symptoms.25 Another explanation for the rapid improvement of urinary bother after RP may be that urinary bother does not correlate with pad use, suggesting that bother is more affected by irritative and obstructive symptoms than by incontinence.26

Fourth, whereas the majority of postoperative patients recovered less of their sexual function scores following RP, they were likely to return to their baseline levels of sexual bother (distress). Although Japanese beliefs regarding sexual dysfunction have changed considerably in recent years, discussion of sexually-related topics continues to be uncommon in Japanese patient-doctor encounters. Japanese patients, unlike their American counterparts, do not report dissatisfaction with their sexual life, even when reporting erectile dysfunction and decreased libido.27,28 In addition, male erectile rigidity contributed to the frequency of sexual intercourse, but not to a satisfactory sexual life for the partner.29 The benefits of BNS on sexual recovery after RP have been reported in several high-volume series30,31 In our study, we also found better recovery of sexual function and bother among those who underwent BNS compared with those who did not. Whereas the sexual function score of the younger patients was better than that of older men, it would appear that erectile dysfunction after RP was more of a burden to the younger patients. Younger men who underwent RP were potentially more interested or motivated to maintain or resume sexual function postoperatively. Thus, younger men were less likely than the older men to return to their baseline levels of sexual bother (distress). These findings will be helpful in counseling men with high sexual activity when they are making a decision about RP.

We acknowledge several limitations in this prospective observational study. First, our study had relatively few patients, consistent with its design as a feasibility study of longitudinal collection. Second, the treatment was not in a randomized fashion but selected by the patient and his urologist. Third, we did not distinguish those who used erectile aids such as type 5 phosphodiesterase inhibitors or vacuum devices after RP. Fourth, there were no documentations of use of α-blockers, or anticholinergics before and after RP. These factors may be significant predictors of urinary or sexual function recovery. Finally, trends in HRQOL might differ for these individuals. A selection bias may have occurred with regard to patients who agreed to participate in this study.

Despite these limitations, our findings must be confirmed or refuted by the longitudinal data of others. A richer understanding of the changes in HRQOL after RP will enable physicians to provide clinically relevant information that allows patients who elect surgery to be comfortable with their choices.

Conclusion

Despite reports of problems with sexuality and urinary continence, general HRQOL was mostly unaffected by RP after 6 months. After RP, urinary incontinence was observed, but urinary irritation and obstruction improved, particularly in patients with moderate/severe LUTS. Adverse effects of RP on sexual function were mitigated by bilateral nerve-sparing procedures up to 5 years after the operation. While a small percent of subjects experienced changes in urinary control, sexual function and IPSS between 2 and 5 years after RP, functional outcomes remained relatively stable in the majority of patients.

Acknowledgments

We would like to thank Emiko Izutsu, Tohoku University Hospital, for assistance with data collection and management.

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