71Archivio Italiano di Urologia e Andrologia 2017; 89, 1 ORIGINAL PAPER Factors affecting surgical margin positivity in robotic assisted radical prostatectomy Mustafa Yuksel, Kaan Karamık, Hakan Anıl, Ekrem Islamoglu, Mutlu Ates, Murat Savas Antalya Training and Research Hospital, Antalya, Turkey. Objectives: After radical prostatectomy, surgical margin positivity is an important indicator of biochemical recurrence and progression. In our study we want to compare the surgical margin positivity rates for retropubic radical prostatectomy (RRP) and robotic assisted radical prostatectomy (RALP) and investigate the factors affecting surgical margin positivity in RALP. Materials and methods: Data from 78 RRP and 62 RALP patients operated from 2011 May to 2016 March were retrospectively screened. Patients in both groups were com- pared in terms of age, postop hematocrit reduction, hospital stay, duration of follow-up, surgical margin positivity, biochemical recurrence and oncologic parameters. In RALP group it was searched the relationship between the surgical margin positivity and prostate specific antigen (PSA), positive biopsy core, biopsy Gleason scoring, pathologic stage and Gleason scoring, lymph node positivity, lymphovascular and perineural invasion, extracapsular extension, seminal vesicle invasion, prostate weight. Results: Patients in the RALP group had lower postop hematocrit reduction and shorter hospital stay (p < 0.001). There was no difference in surgical margin positivity between RALP and RRP groups (37.1% vs. 29.5%, p = 0.341). In RALP group there was a correlation between surgical margin positivity and positive biopsy core number (p = 0.011), pathologic stage (p < 0.001) and Gleason score (p < 0.001), EAU risk classification (p = 0.001), seminal vesicle invasion (p = 0.045), extraprostatic extension (p < 0.001). There was no correlation between prostate weight (p = 0.896), PSA (p = 0.220), biopsy Gleason score (p = 0.266), lymph node positivity (p = 0.140), perineural (p = 0.103) and lymphovas- cular invasion (p = 0.92) with surgical margin positivity. Conclusions: Positive biopsy core number, pathological stage and Gleason score, EAU risk classification, seminal vesicle invasion and extraprostatic extension are correlated with surgical margin positivity in RALP. KEY WORDS: Prostatectomy; Surgical margin; Prostate cancer. Submitted 7 November 2016; Accepted 11 January 2017 Summary No conflict of interest declared. prostatectomy was first used by Binder and Kramer (4) in 2001 and is being applied at greater rates through time. Among the advantages of robotic assisted radical prosta- tectomy (RARP) are technical details such as appropriate mimicking of the wrist maneuvers used in open surgery, 3-dimensional imaging and ability to perform surgery under magnification. In 2008, the open technique was chosen for 44% and the robotic technique was chosen for 53% of the procedures of radical prostatectomy in the USA (5). When the literature is investigated, it appears the hospital stay and transfusion rates are lower for the robotic technique compared to the open tech- nique, though when functional and oncologic results are investigated contradictory results are found (6-9). Additionally the high cost associated with robotic radical prostatectomy has led to questions about the necessity for use of this technique in developing countries such as ours (10). Surgical margin positivity after radical prostatectomy is one of the important causes of biochemical recurrence and progression. When comparing retropubic radical prostatectomy (RRP) and RARP one of the important top- ics of interest is the effect on surgical margin positivity. In this study we compared the surgical margin positivity rates of RRP and RARP and aimed to investigate the factors affecting surgical margin positivity in RARP. MATERIALS AND METHODS The data belonging to 173 patients who underwent RRP or RARP for prostate cancer, without neo-adjuvant thera- py, at our center from May 2011 to March 2016 were ret- rospectively scanned. Our study was in accordance with the Helsinki Declaration and did not gain ethics commit- tee permission as it included retrospective data. While RRP was performed with the classic retropubic technique, the robotic technique used the da Vinci robotic surgical system (Intuitive Surgical, Sunnyvale, CA, USA) with 5 port transperitoneal approach. The operations were performed by 3 different surgeons experienced in open surgery and inexperienced in robotic surgery. Patients with lymph node metastasis risk above 5% according to the Briganti nomogram (11) had extended lymph node dissection (2) performed. For low risk prostate cancer (T1c, PSA < 10, Gleason < 7) patients, a nerve-sparing approach was cho- sen. Patients who underwent RRP had a urethral Foley catheter inserted for 2 weeks, while RARP patients had a catheter inserted for 1 week. The patient age, prostate DOI: 10.4081/aiua.2017.1.71 INTRODUCTION Prostate cancer is the 2nd most common cancer type and is the 5th cause of cancer-related death in men (1). The gold standard treatment for localized prostate can- cer currently is radical prostatectomy (2). Much knowl- edge and experience of the open technique has been gained since radical prostatectomy was modernized by Walsh (3) in 1982. The robotic technique for radical Yuksel_Stesura Seveso 04/04/17 09:28 Pagina 71 Archivio Italiano di Urologia e Andrologia 2017; 89, 1 M. Yuksel, K. Karamık, H. Anıl, E. Islamoglu, M. Ates, M. Savas 72 specific antigen (PSA), positive core number on biopsy, biopsy Gleason scoring, hospital stay, surgical pathology stage according to TNM classification, surgical Gleason scoring, lymph node pos- itivity, surgical margin condition, lymphovascular and perineural invasion, extracapsular extension and seminal vesicle invasion con- ditions, prostate weight, and bio- chemical recurrence during fol- low-up were recorded. Patients were classified as low risk, moder- ate risk and high risk based on biopsy pathology and PSA in accordance with the European Association of Urology (EAU) prostate cancer guidelines. According to TNM surgical stag- ing, patients were divided into T2 and T3-T4. Biochemical recur- rence was defined as postopera- tive PSA rising above 0.2 ng/ml. Thirty-three patients with incom- plete data were excluded from the study. Early oncologic results of 78 RRP and 62 RARP patients were compared in rela- tion to the recorded parameters. Additionally, the factors affecting surgical margin positivity in RARP patients were researched. Statistical analysis Descriptive statistics of data are given as mean, standard deviation, median, frequency and percentage. The distri- bution of variables was measured with the Kolmogorov Smirnov test. Quantitative data were analyzed with the Mann-Whitney U test. Analysis of qualitative data used the chi-square test, with the Fisher test used when chi-square test conditions were not valid. Analyses were completed using the SPSS 22.0 program (SPSS, Chicago, IL, USA). A value of p < 0.05 was accepted as statistically significant. RESULTS The data of patients undergoing retropubic radical prosta- tectomy and robotic assisted radical prostatectomy are shown in Table 1. The follow-up duration for RRP group patients was clearly longer than for RARP patients (p < 0.05). Patients in the RARP group had less postop hematocrit reduction and shorter hospital stays (p < 0.05). While there was no difference between patients of the two groups in terms of biopsy Gleason score and PSA (p > 0.05), surgical stage and Gleason score in the RRP group were higher (p < 0.05). Though surgical margin positivity was observed at a higher rate in the RARP group compared to the RRP group (37.1% vs. 29.5%), this dif- ference did not reach statistical significance (p = 0.341). Additionally, biochemical recurrence was observed at a higher rate in the RRP group (26.9% vs. 16.1%, p = 0.127). The factors affecting surgical margin positivity in patients treated by the robotic assisted radical prostatectomy group are investigated in Table 2. When patients in the RARP group are investigated in terms of surgical margin positiv- ity, a correlation was found between biopsy positive core number, EAU risk classification, surgical stage, surgical Gleason degree, seminal vesicle invasion and extraprosta- tic extension with surgical margin positivity (p < 0.05). Additionally, surgical margin positivity increased the inci- dence of biochemical recurrence (p < 0.05). DISCUSSION Surgical margin positivity in radical prostatectomy is one of the important factors affecting disease recurrence and progression. D’Amico et al. reported that the 2 year bio- chemical recurrence rate in patients with surgical margin positivity (45-55%) was higher compared to patients with organ-limited disease (15-25%) (12). In our study investigating the data of 140 radical prostatectomy patients, surgical margin positivity in RARP group patients increased biochemical recurrence. Though sur- gical stage and surgical Gleason degree were higher in RRP patients, surgical margin positivity in RARP patients was still observed at a higher rate (although difference did not reach statistical significance). We believe this sit- uation may be linked to still being in the learning stage for robotic radical prostatectomy operations. Biochemical recurrence rates were observed to be higher in the RRP group (although difference was not statistical- ly significant), but we believe that this observation may be due to the longer follow up period in the RRP group. When factors affecting surgical margin positivity in robotic radical prostatectomy are investigated, the results of litera- ture appears to be very complex. A study by Liss et al. in RARP patients, found a correlation of surgical margin pos- itivity with PSA (P = 0.012) and PSA density (P = 0.005) Table 1. Comparison of RARP and RRP patients. Robotic assisted Retropubic radical radical prostatectomy prostatectomy p n = 62 n = 78 Mean ± S.D/n-% Med Mean ± S.D/n-% Med Age (year) 63.4 ± 6.8 65.5 63.8 ± 6.3 64.0 0.850 m Hematocrit decrease (%) 3.9 ± 2.2 4.3 7.7 ± 4.1 6.9 0.000 m Hospitalization (day) 4.5 ± 2.1 4.0 8.4 ± 3.4 7.0 0.000 m Follow up (month) 5.5 ± 5.0 3.5 22.6 ± 19.4 17.5 0.000 m PSA (ng/ml) 0-4 4 6.5% 4 5.1% 4-10 37 59.7% 49 62.8% 0.520 X2 10-20 16 25.8% 14 17.9% 20 ˃ 5 8.1% 11 14.1% Pathological stage T2 33 53.2% 55 70.5% 0.035 X2 T3 29 46.8% 23 29.5% Pathology gleason ≤ 6 23 37.1% 44 56.4% 7 34 54.8% 24 30.8% 0.016 X2 8-10 5 8.1% 10 12.8% Surgical margin (-) 39 62.9% 55 70.5% 0.341 X2 (+) 23 37.1% 23 29.5% Seminal vesicle invasion (-) 51 82.3% 65 83.3% 0.867 X2 (+) 11 17.7% 13 16.7% Lymph node (-) 58 93.5% 74 94.9% 0.738 X2 (+) 4 6.5% 4 5.1% Biochemical recurrence (-) 52 83.9% 57 73.1% 0.127 X2 (+) 10 16.1% 21 26.9% m Mann-Whitney u test; X² Chi-square test Yuksel_Stesura Seveso 04/04/17 09:28 Pagina 72 but no correlation was found with clinical stage and biop- sy Gleason score (13). Ficarra et al. found a correlation between surgical margin positivity and biopsy Gleason score, pathologic stage and Gleason score and extraprosta- tic extension but did not find a correlation with PSA (14). Coelho et al. found a correlation between pathologic stage and pathologic Gleason score with surgical margin positiv- ity, while no correlation was found with PSA, biopsy Gleason score and biopsy positive core number (15). In our study we found a correlation of positive biopsy core number, pathologic stage and Gleason score, EAU risk classification, seminal vesicle invasion and extraprostatic extension with surgical margin positivity in RARP. Additionally, no correlation was found with PSA, biopsy Gleason score, perineural and lymphovascular invasion and lymph node positivity. In the literature, there are some studies stating that a small prostate neck may increase the risk of surgical margin positivity (16), though in our study there was no correlation found between prostate weight and surgical margin positivity in RARP patients. When studies of the literature comparing surgical margin positiv- ity rates in robotic assisted radical prostatectomy and retropubic radical prostatectomy are considered, contra- dictory results are found. A study in 2015 (17) investigat- ed 282 RARP and 621 RRP opera- tions and found no difference between the 2 techniques in terms of surgical margin positivity (24.5% vs. 23.1%, p = 0.51). A meta-analysis by Soorikumaran et al. of data considering 22.393 patients showed that surgical margin positivity was higher in the open radical prostatectomy group (22.8%) compared to the RARP group (13.8%) (18). When assessing the results of this study, it should be noted that the patients in the open radical prostatectomy group had higher rates of high risk prostate cancer. Tewari et al. investigated data from 286.876 radical prostatec- tomy patients obtained from 400 studies and found no difference between robotic RP and open RP in terms of surgical margin posi- tivity (19). Additionally, surgical margin positivity appeared to be lower in robotic RP compared to laparoscopic RP. Experience is one of the most important factors affecting onco- logic and functional results in robotic-aided radical prostatecto- my. A study conducted in 2009 on the effects of surgical experi- ence on RARP (20) investigated the results of 700 RARP opera- tions. This study compared the results of the operations from 0- 300, 300-500 and 500-700 and observed that as experience increased the surgical margin positivity rates decreased. A study by Kwon et al. investi- gating 286 patients compared the results of 165 RARP performed by surgeons with no experience of RARP and 121 RARP operations performed by surgeons with experi- ence of RARP (21). In this study, experience of RARP appeared to directly affect surgical margin positivity (24% vs. 34.6%, P = 0.05). As we are still in the early stages of RARP surgery, we believe that our surgical margin positiv- ity rates would decrease in course of time. There are studies investigating the effects of surgical technique on surgical margin positivity in robotic assist- ed radical prostatectomy. A study in 2009 did not find an effect on surgical margin positivity for nerve-sparing extrafascial and intrafascial techniques (22). Chung et al. (23) investigated the effect of transperitoneal and extraperitoneal robotic prostatectomy on surgical margin positivity and obtained similar rates for both techniques. Similarly bladder neck-sparing did not have an effect on surgical margin positivity (24). In a study published in 2009 (25) incision after suture ligation of the dorsal venous complex had greater rates of apical surgical mar- gin positivity compared to only cold incision (p = 0.02). One of the points where RARP appears to be superior to 73Archivio Italiano di Urologia e Andrologia 2017; 89, 1 Factors affecting surgical margin positivity in robotic assisted radical prostatectomy Table 2. Factors affecting surgical margin positivity in robotic assisted radical prostatectomy. Surgical margin (-) Surgical margin (+) robotik prostatectomy Robotic prostatectomy p n = 39 n = 23 Mean ± S.D/n-% Med Mean ± S.D/n-% Med Age (year) 63.2 ± 6.6 65.0 63.9 ± 7.3 66.0 0.672 m Positive biopsy core number 3.3 ± 2.2 3.0 5.3 ± 3.0 5.0 0.011 m PSA (ng/ml) 0-4 3 7.7% 1 4.3% 4-10 25 64.1% 12 52.2% 0.220 X2 10-20 11 28.2% 5 21.7% 20 ˃ 0 0.0% 5 21.7% Biopsy gleason ≤ 6 29 74.4% 14 60.9% 7 10 25.6% 6 26.1% 0.266 X2 8-10 0 0.0% 3 13.0% Risk High risk 0 0.0% 7 30.4% Intermediate risk 19 48.7% 9 39.1% 0.001 X2 Low risk 20 51.3% 7 30.4% Prostatectomy gleason ≤ 6 21 53.8% 2 8.7% 7 14 35.9% 20 87.0% 0.000 X2 8-10 4 10.3% 1 4.3% Lymphovascular invasion (-) 30 76.9% 13 56.5% 0.092 X2 (+) 9 23.1% 10 43.5% Perineural invasion (-) 10 25.6% 2 8.7% 0.103 X2 (+) 29 74.4% 21 91.3% Lymph node invasion (-) 38 97.4% 20 87.0% 0.140 X2 (+) 1 2.6% 3 13.0% Seminal vesicle invasion (-) 35 89.7% 16 69.6% 0.045 X2 (+) 4 10.3% 7 30.4% Biochemical recurrence (-) 37 94.9% 15 65.2% 0.002 X2 (+) 2 5.1% 8 34.8% Stage T2 29 74.4% 4 17.4% 0.000 X2 T3 10 25.6% 19 82.6% T2A 10 25.6% 0 0.0% T2B 1 2.6% 0 0.0% T2C 18 46.2% 4 17.4% T3A 6 15.4% 12 52.2% T3B 4 10.3% 7 30.4% Extraprostatic extension (-) 29 74.4% 0 0.0% 0.000 X2 (+) 10 25.6% 23 100% m Mann-Whitney u test; X² Chi-square test Yuksel_Stesura Seveso 04/04/17 09:28 Pagina 73 Archivio Italiano di Urologia e Andrologia 2017; 89, 1 M. Yuksel, K. Karamık, H. Anıl, E. Islamoglu, M. Ates, M. Savas 74 RRP is the low rate of postoperative blood transfusion and shorter hospital stay (26, 27). In our study, the RARP group patients had lower postoperative hemoglo- bin decrease and shorter hospital stays compared to patients in the RRP group. One of the limitations of our study is that the functional results of both radical prostatectomy techniques were not included as it was retrospective. Additionally due to the retrospective nature of the study, we could not inves- tigate the effects on surgical margin positivity of stan- dardizing the surgical technique. In addition to these points, our results reflect results from the learning stage. We believe that a future update will negate this problem. CONCLUSIONS Biopsy positive core number, surgical stage and Gleason degree, EAU risk classification, seminal vesicle invasion and extraprostatic extension are correlated with surgical margin positivity in RARP. REFERENCES 1. 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Correspondence Mustafa Yuksel, MD (Corresponding Author) - drmustafayuksel@outlook.com Kaan Karamık, MD - Hakan Anıl, MD - Ekrem Islamoglu, MD Mutlu Ates, MD - Murat Savas, MD Department of Urology, Antalya Training and Research Antalya EğitimAraştırmaHastanesi, VarlıkMh. 07050 Muratpaşa/Antalya, Turkey Yuksel_Stesura Seveso 04/04/17 09:28 Pagina 74