Outcome Changes after Diverse Radical Prostatectomy among Prostate Cancer Patients: Comparison of One and Five Years of Follow-Up

Prostate cancer develops slowly and is frequently diagnosed in elderly men, and its treatments are associated with adverse effects on the urinary and sexual function of patients [1]. Radical prostatectomy (RP) may reduce the disease-specifi c mortality of patients with prostate cancer, although this approach has been shown to have long-term negative complications with no improvement in overall patient survival [2]. Chen et al. [3], recommended that longitudinal measurement of patients’ reported outcomes is crucial because of the time-dependent nature of symptom development after treatment.


Introduction
Prostate cancer develops slowly and is frequently diagnosed in elderly men, and its treatments are associated with adverse effects on the urinary and sexual function of patients [1]. Radical prostatectomy (RP) may reduce the disease-specifi c mortality of patients with prostate cancer, although this approach has been shown to have long-term negative complications with no improvement in overall patient survival [2]. Chen et al. [3], recommended that longitudinal measurement of patients' reported outcomes is crucial because of the time-dependent nature of symptom development after treatment.
Urinary incontinence and sexual dysfunction are common long-term consequences of RP [4]. Bill-Axelson et al. [5], conducted a longitudinal survey in Sweden and found that men with prostate cancer reported more leakage, impaired erections, and greater distress after the RP procedure.
Moreover, fi ve years after RP, patients continued to experience urinary incontinence and sexual dysfunction [2].

Urinary incontinence
Urinary incontinence (defi ned as frequent urinary leakage or no control) is one of the major immediate complications that may occur after RP [1,6]. Although the severity of urinary incontinence often decreases with time after RP [6][7][8], previous studies have demonstrated that 8% to 87% of patients still experience urinary incontinence at six months and 5% to 44.5% remain incontinent at one to two years after surgery [7][8][9][10][11][12]. Moreover, up to 50% of patients report some degree of incontinence two years after RP [3], even after pelvic fl oor muscle exercise intervention.
Lin et al. [13], used a one-hour pad test to examine urinary incontinence after RP. These authors found that even when patients were given pelvic muscular fl oor exercise for three months, there was still an average of 9.27 cc of urinary leakage in the exercise group, as compared to 27.11 cc of urine leakage in the group without exercise. Moreover, fi ve years after RP, 15.3% of the patients who were treated with RP still experienced urinary incontinence [2].

Sexual dysfunction
Another complication of RP is impotence (defi ned as insuffi cient erections for intercourse) [2]. Impotence occurs in 25% to 100% of patients after prostatectomy [14][15][16][17][18]. In fact, 80% to 90% of patients reported diffi culty with erections after prostatectomy [10,19], and previous studies have indicated that the recovery of sexual function may take up to two years after RP [20][21][22][23], with 60% of men still reporting sexual dysfunction two years after RP [19,24,25]. However, another study conducted by Zielinski [2], showed that fi ve years after a prostate cancer diagnosis and the RP procedure, 79.3% of men continued to experience sexual dysfunction. A study conducted by Soares et al., showed that the fi ve years long term potent rate was 76.6% of previously potent, non-diabetic, and aged <70 years after RP with bilateral nerve preservation [26].
Cancer-related treatments may cause acute or delayed side effects and long-term complications [27]. Although urinary incontinence and sexual dysfunction after RP treatment have been well documented, information about long-term follow-up remains sparse in Taiwan. According to the literatures, prostate cancer patients with local disease have a fi ve-year survival rate of nearly 100% [21,28]. Longitudinal measurements are therefore important to understand the long-term changes that can occur as a consequence of surgical procedures for prostate cancer.
In addition, one study reported that men who received RP were likely to experience profound long-term symptoms of distress [5]. One previous study estimated that 30%  within fi ve years after treatment [29]. To clarify whether these fi ndings are applicable to Taiwanese patients, we also explored patients' perceived physical symptoms of distress and their changes over time in this study.

Aims
The purpose of this study was to explore the changes in complication outcomes after two types of RP procedures among prostate cancer patients and to assess the perceived symptoms of distress following RP.

Design
This study applied a comparison design with pre-and post-tests. All participants were assessed for urinary function,

Setting and samples
There were two stages for the recruitment and assessment

Instrument
Urinary incontinence scale: This scale was developed by the fi rst author to assess the urinary incontinence of prostate cancer patients after the RP procedure [30]. The scale includes eight items and indicates the severity of each item using a fi ve-point Likert scale, with 1 corresponding to "never occurs" and 5 to "always occurs". The possible scores ranged from 8 to 40, with higher scores indicating more severe incontinence.
The construct validity of this scale was determined using an explorative factor analysis, and the results were found to account for 60.28% of the variance. The scale validity was also demonstrated by criterion-related validity, and the results showed a good correlation with the University of California, Los Angeles Prostate Cancer Index (UCLA-PCI) urinary function subscale and the one-hour pad test. The internal consistency was examined with Cronbach's alpha, and a previous study reported a coeffi cient value of 0.90 [30]. In this study, the alpha coeffi cient was 0.90 at one year and 0.91 at fi ve years after RP. and intercourse satisfaction. The scores range from 5 to 25 [31]. In this index, ED is categorized into fi ve types based on the following scores: severe (5-7), moderate (8)(9)(10)(11), mild to moderate (12)(13)(14)(15)(16), mild (17)(18)(19)(20)(21), and no ED (22)(23)(24)(25) [31,32].
Previous studies demonstrated the good validity and reliability of this questionnaire when it was used in RP recipients [20].
The Cronbach's  in this study was 0.87 at the one-year examination and 0.85 at fi ve years after RP.

Personal features and disease-related variables:
Several demographic items were added to the questionnaire, including age, marital status, education level, employment status, and exercise habits. The following disease-related variables were also included: operation type, nerve-sparing surgery, comorbidities (such as diabetics, hypertension, and myocardial ischemia), and the patient's history of use of erectile aids (such as phosphodiesterase inhibitors, e.g., sildenafi l (Viagra) and tadalafi l (Cialis)). One self-reported 0-10 numeric scale was used to assess the participants' perceived physical symptoms of distress, with 1=no distress and 10=extreme distress. Higher scores indicated that more physical symptoms of distress were perceived. We also used a questionnaire to ask patients whether they were experiencing urinary incontinence (defi ned as Yes/ No) at the fi ve-year follow-up examination.

Ethical considerations
This study was approved by the study participants' hospital's institutional review board (No. EMRP-096-084). A written consent form informed the participants that participation was voluntary and that there were no physical, social, or legal risks involved in the research.

Characteristics of the participants
A summary of the personal characteristics of the study participants is presented in Table 1. A total of 49 participants completed both stages of the study: 27 from the open surgery procedure group and 22 from the laparoscopic procedure group. The mean age of the participants was 65.4 years (SD = 6.7 years), with a range from 47 to 79 years. The majority of the patients were married (95.9%), with a similar distribution of patients with more or less than 9 years of education. Most of the participants (65.3%) exercised regularly. The majority of participants had not received nerve-sparing surgery (57.1%) or alternative therapy (85.7%). Many of the participants (59.2%) had other diseases (hypertension, diabetes, and heart disease). To improve their sexual function, 77.6% of patients received erectile aids.
Nearly all personal and disease-related characteristics of the participants were similar between the groups treated by open and laparoscopic RP (test by Pearson X 2 , all p>0.05), except for the rate of nerve-sparing surgery (X 2 =4.30, p<0.05), which was treated as a covariate in the GEE model.

Outcome changes over time
Urinary incontinence: As shown in Table 2, 46.9% of the participants reported experiencing urinary incontinence, including 44.4% in the open surgery group and 50.0% in the laparoscopy group, at fi ve years after RP. As shown in Table  3, the average urinary incontinence mean score in the open surgery group at one year post-RP was 20.4 (SD=8.4), and the mean score decreased to 12.9 (SD=11.7) at fi ve years post-RP. In the laparoscopy group, the one-year urinary incontinence mean score was 9.7 (SD=6.1), which decreased to 5.5 (4.8) at fi ve years after the procedure. Both the RP group (all p<0.01) and the number of years after RP (all p<0.05) were associated with signifi cant differences in urinary incontinence, indicating that all RP patients experienced signifi cant improvements in their urinary function over time.
Sexual dysfunction: In this study, 59.1% of the participants reported experiencing severe sexual dysfunction at fi ve years after surgery, including 66.7% in the open surgery group and 50% in the laparoscopy group ( Table 2). The mean score for the IIEF in the open surgery group at one year post-RP was 7.51 (SD=4.06) compared with 8.0 (2.7) at fi ve years after the procedure. In the laparoscopy group, the mean one-year IIEF score was 8.1 (SD=4.3) compared with 10.9 (6.1) at fi ve years post-RP. Neither the RP group (all p>0.05) nor the number of years after RP (all p>0.05) was associated with a signifi cant difference in sexual dysfunction (Table 3), indicating that even though the mean scores for the IIEF increased, the patients who   Effects of the RP procedure on patient outcome: Table   4 shows the changes in patient outcomes based on the RP group. After controlling for nerve-sparing surgery, the GEE

Discussion
This study was performed to examine the changes in the complications and perceived physical symptoms of distress after two types of RP procedures among prostate cancer patients. We will discuss the complication-related outcomes (urinary incontinence and sexual dysfunction) and perceived physical symptoms of distress sequentially below.
This study found that the study participants' urinary incontinence showed signifi cant changes after both open and laparoscopic RP. These results indicated that the RP recipients' urinary incontinence decreased over time. However, 44.4%  and 50.0% of the study participants still reported suffering from urinary incontinence at fi ve years post-RP. These results are similar to those reported in a study by Bill-Axelson et al. [5], which found that patients consistently reported urinary leakage, impaired erections, and distress after eight years of follow-up. However, the urinary incontinence rates for both groups are higher than those reported by Zielinski et al. [2], Potosky et al. [33], and Soares et al. [26], (15%, 14-16%, and 6.2% respectively). These differences in the rates of incontinence may be related to the use of diverse measurement tools, different defi nitions of urinary incontinence, and the fact that the present study used a single question to ask participants whether they experienced urine leakage [2,33].
As shown in Table 1, we found that nerve-sparing surgery was a confounding variable (p<0.5), and after controlling for this variable, the results ( and these results are consistent with the fi ndings of a previous study [33].
As shown in Table 2 Sexual dysfunction is often more complex than the biology of ED [35]. Some patients in this study reported penile shortening and never regained erectile function after RP. These complications dominated their daily life and decreased their quality of life. These results support those described by Resnick et al. [36], who found that at 15 years after surgical treatment, 87% of prostate cancer patients were still experiencing sexual side effects.
A study by Bill-Axelson et al. [5], indicated that patients who underwent an RP procedure still suffered from distress eight years later. These authors found that the mean average perceived physical symptoms of distress showed signifi cant decreases over time in two groups of RP patients with signifi cant differences observed at 5 years, but not 1 year, post-surgery. After controlling for nerve-sparing surgery as a confounding variable, the participants' perceived physical symptoms of distress showed signifi cant changes in both groups in our present study. In particular, our results showed that the RP recipients' perceived physical symptoms of distress decreased over time. These results support a previous study showing that nearly one-third of prostate cancer patients experienced clinically relevant distress, but that these symptoms of distress decreased within fi ve years after treatment [28].
We used the mean score for urinary incontinence and the IIEF at fi ve years post-RP for the two surgical groups to conduct a power analysis to test this study's effect sizes. The results showed that when the power was set to 0.80 and the alpha was 0.05 (two-tailed), the effect sizes were 0.80 and 0.64, respectively (moderate effect sizes) [37]. Our fi ndings with regard to the sample size calculation provide a basis for further research.

Limitations of this study and recommendations for future research
The present study has some limitations. First, our participants were only recruited from one hospital in southern Taiwan, which may have limited the ability to generalize the results of this study to other populations. Second, there was a four-year interval between the two time points of follow-up; therefore, we lost contact with some patients, which led to a decrease in the study sample size at fi ve years. In addition, the perceived physical symptoms of distress may have been related to psychological problems, such as anxiety or depression, which we did not take into account in our study. Thus, further studies are recommended. Additionally, this study only examined the changes in complications for fi ve years, and further studies should be performed to assess the longer-term outcomes after RP.

Conclusion
The results of this study demonstrate that prostate cancer patients who have undergone RP experience long-term adverse complications. These results provide new information about the long-term complications of two different RP approaches for clinically localized prostate cancer that will help guide treatment decisions. Oncological and urological nurses should be aware of the complications experienced, should recognize the changes in adverse outcomes, and should consider early intervention to decrease the adverse effects in cancer survivors.