Health-related Quality of Life in the First Year after Laparoscopic Radical Prostatectomy Compared with Open Radical Prostatectomy

Jpn J Clin Oncol 2014;44(7)686 691 doi:10.1093/jjco/hyu052 Advance Access Publication 3 May 2014 Health-related Quality of Life in the First Year after Laparoscopic Radical Prostatectomy Compared with Open Radical Prostatectomy Katsuyoshi Hashine *, Takeshi Nakashima, Hiroyuki Iio, Yoshiteru Ueno, Shinjiro Shimizu and Iku Ninomiya Department of Urology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan *For reprints and all correspondence: Katsuyoshi Hashine, Department of Urology, National Hospital Organization Shikoku Cancer Center, 160 Minamiumemoto, Matsuyama 791-0280, Japan. E-mail: khashine@shikoku-cc.go.jp Received February 18, 2014; accepted March 28, 2014 Objective: To assess health-related quality of life in the first year after laparoscopic radical prostatectomy compared with that after open radical prostatectomy. Methods: The subjects were 105 consecutive patients with localized prostate cancer treated with laparoscopic radical prostatectomy between January 2011 and June 2012. Health-related quality of life was evaluated using the International Prostate Symptom Score, Medical Outcome Study 8-Items Short Form Health Survey (SF-8) and Expanded Prostate Cancer Index Composite at baseline and 1, 3, 6 and 12 months after surgery. Comparisons were made with data for 107 consecutive patients treated with open radical prostatectomy between October 2005 and July 2007. Results: The International Prostate Symptom Score change was similar in each group. The laparoscopic radical prostatectomy group had a better baseline Medical Outcome Study 8-Items Short Form Health Survey mental component summary score and a better Medical Outcome Study 8-Items Short Form Health Survey physical component summary score at 1 month after surgery. In Expanded Prostate Cancer Index Composite, obstructive/irritative symptoms did not differ between the groups, but urinary incontinence was worse until 12 months after surgery and particularly severe after 1 month in the laparoscopic radical prostatectomy group. The rate of severe urinary incontinence was much higher in the laparoscopic radical prostatectomy group in the early period. Urinary bother was worse in the laparoscopic radical prostatectomy group at 1 and 3 months, but did not differ between the groups thereafter. Urinary function and bother were good after nerve sparing procedures and did not differ between the groups. Bowel and sexual function and bother were similar in the two groups. Conclusion: Urinary function in the first year after laparoscopic radical prostatectomy is worse than that after open radical prostatectomy. Key words: health-related quality of life laparoscopic radical prostatectomy SF-8 EPIC INTRODUCTION Radical prostatectomy is widely used as curative treatment for localized prostate cancer. This surgery was performed by open radical prostatectomy (ORP) until the late 1990s, but can now be achieved using laparoscopic radical prostatectomy (LRP) and robot-assisted LRP (RALP). LRP was introduced in 1997 by Schuessler et al. (1) and Raboy et al. (2) butdifficulties with the technique and concerns about the results initially delayed widespread use of LRP in Japan. However, after Guillonneau et al. (3) reported the outcomes of LRP in 1999, the technique has been developed in Japan (4,5) and has become common treatment for localized prostate cancer. Good oncological and functional outcomes are important in radical prostatectomy. The oncological outcome is judged similarly in any surgical procedure. A positive resection margin occurs at rates of 9.0 38.8% in LRP and 11.5 43.6% # The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Jpn J Clin Oncol 2014;44(7) 687 in ORP (6 8), while the prostate-specific antigen (PSA) failure-free rate is 75.6 88.7% in LRP and ORP (9 11). Functional outcomes after LRP have been shown to be similar or worse compared with ORP. Thus, Anastasiadis et al. (12) found similar rates of urinary incontinence after LRP and ORP, whereas Egawa et al. (4) reported delayed recovery of urinary incontinence after LRP. In these studies, urinary incontinence was defined based on use of pads, but similar conflicting results have been found using a health-related quality of life (HRQOL) tool such as the University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI). For example, Namiki et al. (13,14) found that recoveries of urinary function and sexual function were delayed in LRP compared with ORP, whereas Ball et al. reported similar outcomes for urinary incontinence after LRP and ORP (15). Recently, new disease-specific QOL, Expanded Prostate Cancer Index Composite (EPIC), was developed to make up for the disadvantage of UCLA-PCI. However, there are very few reports describing the QOL using EPIC in Japanese patients, especially in regard to a prospective study. In the current study, HRQOL after treatment of localized prostate cancer by LRP or ORP was assessed using EPIC, with the goal of comparing the functional outcomes of LRP and ORP. PATIENTS AND METHODS LRP was performed for 105 consecutive patients with clinically localized prostate cancer between January 2011 and June 2012. The indication for surgery has been described elsewhere (16). Briefly, surgery was performed regardless of the risk classification. Each patient selected their own therapy after being informed of the various options. During this period, only LRP was performed because ORP had been shifted completely to LRP. For this reason, comparative data were used for 107 consecutive patients treated by ORP between October 2005 and July 2007. In this period, only ORP was performed. Our procedure for LRP involves an extraperitoneal approach and an antegrade procedure. After reconstruction of the posterior structure, vesicourethral anastomosis was performed with a running suture. All LRP procedures were performed by the same surgeon (K.H.) or the surgeon s team in his presence. ORP was performed using an open retrograde procedure with Walsh s technique by two staff urologists or under their supervision. An HRQOL survey was performed before surgery (0-month) and at 1, 3, 6 and 12 months after surgery. This survey was approved by the Institutional Review Board and written informed consent to this study was obtained from all patients. The survey was performed as a self-assessment with no interview. The International Prostate Symptom Score (IPSS) and the Japanese version of the Medical Outcome Study 8-Items Short Form Health Survey (SF-8) were used to assess general HRQOL. On the SF-8, the physical component summary (PCS) and mental component summary (MCS) scores were used. EPIC was used for assessment of diseasespecific HRQOL. On the EPIC questionnaire, the daily use of pads was evaluated and severe urinary incontinence was defined as use of 3 pads each day. The domains of hormone function and bother were omitted because only a few patients received androgen deprivation therapy (ADT), which was used in a neoadjuvant setting only. Group comparisons were performed by Mann Whitney U-test and x 2 test. Two-tailed P values,0.05 were considered significant. SPSS ver. 20.0J was used for all statistical analyses. RESULTS The characteristics of the patients in the LRP and ORP groups are shown in Table 1. The LRP group had a lower PSA level and a better clinical stage and Gleason score compared with the ORP group. Age and the rates of neoadjuvant ADT and nerve sparing procedures were similar in the two groups. There was no significant difference for positive resection margin in both groups. The average answer rate of each HRQOL survey was 85.1% in the LRP group and 82.1% in the ORP group. IPSS showed similar changes in the LRP and ORP groups with a significantly worse score at 1 month compared with baseline, but a return to baseline after 3 months and improvement thereafter (Fig. 1). On the SF-8, the LRP group had a Table 1. Characteristics of patients undergoing laparoscopic radical prostatectomy (LRP) and open radical prostatectomy (ORP) LRP ORP P value Number 105 107 Age (years) Median 66.0 67.0 0.255 Range 51 78 51 79 Clinical stage T1 74 65,0.001 T2 31 34 T3 0 8 PSA (ng/ml) Median 7.56 9.77 0.007 Range 1.66 28.40 1.29 88.68 Gleason score 6 30 19 0.111 7 43 38 8 32 50 NADT 10 6 0.310 Nerve sparing 12 12 1.000 Positive resection margin 30 38 0.305 NADT, neoadjuvant androgen deprivation therapy.

688 QOL after laparoscopic radical prostatectomy better MCS score at baseline and a better PCS score at 1 month after surgery. At 3 months after surgery, the PCS and MCS scores did not differ between the groups. The PCS score in the LRP group was worse at 1 month compared with baseline, and then the score returned toward baseline gradually, but was still significantly worse after 12 months compared with baseline. The PCS score in the ORP group recovered sooner than that in the LRP group. The change in the MCS score improved after 3 months in both groups (Fig. 2). Urinary function based on EPIC scores was better in the LRP group at baseline, but after surgery the score for the LRP group was worse than that for the ORP group until 12 months. The difference between the groups gradually became smaller, but was still significant at 12 months. Obstructive/irritative symptoms did not differ between the groups at all HRQOL survey points. Urinary incontinence was worse after surgery, particularly after 1 month, and the rates of severe incontinence were high in both groups, at 69.0% in the LRP group and 45.7% in the ORP group. These rates improved to 41.6 and 13.1% after 3 months, 13.5 and 4.9% after 6 months, and 2.2 and 4.7% after 12 months, respectively. The rates for severe incontinence differed significantly until 3 months, but showed no difference between the two groups from 6 months onwards. Urinary bother was significantly worse in the LRP group at 1 and 3 months, but not after 6 months. The differences at 1 and 3 months were small compared with those for urinary incontinence (Fig. 3). Bowel function and bother, and sexual function and bother did not differ between the groups at any time point. In both groups, bowel function was worse at 1 month compared with baseline and recovered at 3 months. Sexual function was worse after surgery and did not recover, but sexual bother was stable (Fig. 4). In patients who underwent nerve sparing surgery, urinary function and bother did not differ at any time after LRP and ORP. The EPIC score for urinary incontinence was good for these patients in the LRP group: 50.5 at 1 month and 92.5 at 12 months. The rate of severe urinary incontinence was only 20% in the LRP group after 1 month and no patient who underwent nerve sparing LRP had severe incontinence after 3 months. Figure 1. Mean (+SD) of International Prostate Symptom Score according to surgical methods. LRP, laparoscopic radical prostatectomy; ORP, open radical prostatectomy; SD, standard deviation. DISCUSSION Radical prostatectomy is a common curative treatment for localized prostate cancer. In this procedure, both oncological outcomes and functional outcomes based on HRQOL are important. Radical prostatectomy has been developed from an open surgery to a laparoscopic procedure and RALP, with improved surgery made possible by magnification of the view of the anatomy around the prostate. Improved surgical techniques should lead to good functional outcomes, but several reports have suggested that urinary incontinence, in particular, is a major problem after LRP because it reduces HRQOL (4,5,11). Figure 2. (A) Mean (+SD) of physical component summary scores according to surgical methods. (B) Mean (+SD) of mental component summary scores according to surgical methods. *P, 0.05 LRP vs. ORP.

Jpn J Clin Oncol 2014;44(7) 689 Figure 3. (A) Mean (+SD) of Expanded Prostate Cancer Index Composite (EPIC) scores for urinary function according to surgical methods. (B) Mean (+SD) of EPIC scores for urinary bother according to surgical methods. (C) Mean (+SD) of EPIC scores for urinary irritative/obstructive according to surgical methods. (D) Mean (+SD) of EPIC scores for urinary incontinence according to surgical methods. *P, 0.05 LRP vs. ORP. In this study, we examined general and disease-specific HRQOL after LRP using the SF-8 and EPIC. General HRQOLwasdecreasedbyLRP,butonlytoasmallextentat 1 month after LRP due to the low invasiveness of the procedure. However, recovery to baseline of general HRQOL occurred more quickly after ORP. The cause of delayed recovery in general HRQOL after LRP is unclear. The grade of urinary continence is not related to general HRQOL in this study, but similar findings for general HRQOL after LRP have been reported (13,14). Disease-specific HRQOL after LRP was influenced by low urinary function and urinary bother, especially in the early post-operative phase compared with ORP. Worsening of urinary incontinence in this phase has also been found in previous studies (11,13,14). Recovery of urinary continence after LRP may be similar to or worse than that after ORP based on a recent meta-analysis (16,17). The rate of recovery of urinary continence at 12 months is 82 100% after LRP and 80 97% after ORP, but only 2.9 55.0% in LRP at 1 month (4,11,16), which is lower than after ORP (14,15). However, the definition of urinary incontinence varies and a randomized clinical trial (RCT) has not been performed, which makes it difficult to compare the effects of LRP and ORP with certainty. Urinary incontinence has been evaluated based on the use of pads in many early studies, but this approach has gradually been replaced by evaluation of HRQOL using questionnaires suchastheucla-pciorepic(15,18). Two recent RCTs (19,20) comparing LRP and RALP, but not ORP, have produced important conclusions. Using EPIC, Porpiglia et al. (19) found that the continence rate was higher in the RALP group at every time point, whereas Asimakopoulos et al. (20) found no significant difference for time to continence, but that the each point was lower after LRP. These results support delayed recovery or worsening of continence after LRP compared with RALP, and a meta-analysis suggests that RALP results in similar urinary function to ORP. Thus, this indirect comparison suggests that ORP might be superior to LRP in this respect. The reasons for delayed recovery or worsening of urinary function after LRP are unclear. Moreover, these two RCTs (19,20) are of note that.80% of the patients received nerve sparing surgery and this differs from our predominantly non-nerve sparing cohort. In our study, patients who received nerve sparing surgery had earlier recovery of urinary incontinence and there was no difference in urinary function and bother between LRP and ORP for these patients. Nerve sparing also results in good recovery of sexual function, as well as urinary function (21). Kaya et al. (22) found that the quality of nerve sparing significantly influenced urinary function and that completely sparing at least one neurovascular bundle had a dramatic effect on the

690 QOL after laparoscopic radical prostatectomy Figure 4. (A) Mean (+SD) of EPIC scores for bowel function according to surgical methods. (B) Mean (+SD) of EPIC scores for bowel bother according to surgical methods. (C) Mean (+SD) of EPIC scores for sexual function according to surgical methods. (D) Mean (+SD) of EPIC scores for sexual bother according to surgical methods. recovery of urinary continence. Based on previous results with LRP, ORP and RALP, we suggest that the poorer recovery in non-nerve sparing cases after LRP may be due to limited 2D vision and movement of the forceps limited by the port, despite the magnified view. There are many benefits in LRP, including more accurate dissection due to the magnified view and a clear view due to less bleeding compared with ORP. However, these benefits may not contribute to the functional outcome. In LRP, all surgical procedure must be done viewing only 2D image. The 2D image in LRP may be disadvantageous to an accurate anastomosis between the bladder neck and the urethra comparing ORP or RALP. Incorrect anastomosis may cause the damage of the urethral sphincter and have an influence on urinary continence. Further improvement of techniques may permit earlier recovery of urinary incontinence, including the method of dorsal vein complex ligation, posterior reconstruction, anterior reconstruction and total reconstruction, (23,24) and this may lead to improvement of post-operative HRQOL. There were some limitations in the study. First, the learning curve was different in the two groups. The survey was started after treatment of 80 cases in the LRP group, but after 350 cases in the ORP group. However, the positive surgical margin was similar in the two groups and learning curves were similar based on the resection margin. Also, because the operation method completely shifted from ORP to LRP, understanding of the anatomy was more advantageous in LRP. During this study period, there was no change of the surgical procedure about LRP. So the difference of the QOL was not observed even if LRP group divided into two groups, the first half and the latter half. However, ORP requires.200 cases to reach a performance plateau, whereas LRP requires more cases (25,26). The learning curve is related to urinary incontinence (27) and may not have reached a plateau in our LRP cohort. Second, only a few patients were treated with nerve sparing. Sexual function is related to HRQOL, but only 10% of the patients wanted preservation of sexual function, which prevented a more detailed examination of this issue. Third, this study was retrospective and performed in a small cohort. Despite these limitations, the results provide important information on HRQOL after LRP. In conclusion, LRP is an important surgical technique, but does not improve HRQOL. Urinary function and bother were worse after LRP compared with ORP, especially in the early post-operative phase, and many patients had severe incontinence in this phase. These findings suggest that further improvements in LRP are needed to maintain urinary function post-operatively.

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