Initial Experience and Assessment of Surgical Margins after Robotic Assisted Radical Prostatec to my at a Mexican University General Hospital

Background: Prostate Cancer (PC) is the most common malignant neoplasm in men and it’s the second cause of cancer specific mortality. The finding of Positive Surgical Margins (PSMs) after Radical Prostatectomy (RP) is an


Background
Prostate Cancer (PC) is the most common malign neoplasm in elderly men. Radical Prostatectomy (RP) has been able to provide favorable oncologic control and a prolonged survival for localized PC by reducing the risk of metastasis and local tumor progression [1].
Robotic-assisted surgery continues moving forward and promises to play a major role in the field of urology.

Advantages of this resource
Low blood loss, low postoperative pain, short hospital stay, and speedy patient recovery, have made Robotic-Assisted Radical Prostatectomy (RARP) more common in the treatment armamentarium for PC [2].
After RP, pathologic assessment of tumor's cellular differentiation (Gleason score) and pathologic stage, with preoperative PSA, can be used for staging patients in risk groups, predict outcomes (such as Biochemical Recurrence (BR) risk) and guide immediate treatment [3].
Avoiding Positive Surgical Margins (PSMs) after RP depicts the most important oncologic factor associated with the surgical procedure of RP for PC. Despite the debate of the influence of PSMs on long-term outcome, patients with PSMs have an increased risk for BR when compared to patients with Negative Surgical Margins (NSMs) [4].
Only a few studies (multi-institutional or meta-analysis) have shown a benefit of RARP versus Open Radical Prostatectomy (ORP) in reducing the rate of PSMs [5].
A series of patients without adjuvant treatment showed that those with PSMs have a 57.5% disease-free survival at 5 years [6]. However, disease-free survival at 10 years for those with focal PSMs and extensive PSMs varies significantly between 64% to 38%, respectively [7].

Materials and Methods
An observational, descriptive, transversal, retrospective study was carried out. A review of clinical records from patients with diagnosis of PC that underwent RARP between December 2014 to December 2017 at our urology department was performed. The following variables were analyzed: age, PSA value, T clinical stage, biopsy's Gleason score, perineural invasion, lymphovascular invasion, surgical specimen's Gleason score, pathologic stage, and biochemical recurrence, with the aim of identifying the variables associated with PSMs. Continuous variables with normal distribution are expressed as mean and Standard Deviation (SD), otherwise they are expressed as median and range. Categorical variables are expressed as an absolute value and percentages. For the statistical analysis we used the Chi-squared test and SPSS v.23.0. Results were considered statistically significant if p value was <0.05.

Results
Patient demographics are shown in table 1 and 2. On statistical analysis, PSA level in patients with PSMs was higher than in patients with NSMs, having a significant correlation (p=0.021). When assessing the most frequent regions of PSMs, it was found that the most common site was the apex, followed by the posterior part of the prostate (Graph 1).

P value
Clinical Stage (cT)     Biopsy's Gleason score underestimated the patients, since an increase in the Gleason score of the surgical specimens was found. However, the most frequent Gleason score in patients with PSMs was 3+3=6 (27.9%). No association was found when correlating surgical specimen's Gleason score and PSMs (P 0.57) (Graph 2).

Discussion
PSMs after RP in prostate cancer patients are considered a significantly predictive factor for BR and local recurrence, as well as for the necessity for adjuvant treatment.
In our study, the rate of PSMs is comparable with other reports. PSMs rate was significantly associated with tumor pathologic stage, as reported globally [8]. Other series report PSMs rates that oscillate between 11% to 37% after ORP, 11% to 30% after Laparoscopic Radical Prostatectomy (LRP), and 9.6% to 26% after RARP [9]. Coelho RF, et al. [10] remarked that clinical stage was the only preoperative independent variable associated with PSMs after RARP.
While most studies report similar PSMs rates for both surgical procedures, recent data has found that patients who undergo RARP are, in fact, more likely to have PSMs than those who undergo ORP [12].
In this study, pathologic stage, PSA and perineural invasion were significantly associated with PSMs rate.
Tewari A, et al. [13] concluded in an extensive systematic review that PSMs rates are equivalent for both ORP and RARP. Despite discussion about the true incidence of PSMs in these surgical procedures, it is not known whether the finding of PSMs predicts a greater or lesser risk depending on whether ORP or RARP are performed.
No consensus has been reached on the most frequent PSMs region after ORP, LRP, and RARP, and which of these regions are associated with BR. According to multiple studies, the most common PSMs site after RARP is the prostate apex [14]. In our series, the most frequent region was the prostate apex (>40%), followed by the posterior region (25%), the finding of increased PSMs at the prostatic apex can be explained by at least 3 important surgical aspects: 1) there is no obvious anatomical boundary between the prostatic apex and the external urinary sphincter, therefore, to maximize urethral length, apical surgical margins are often compromised by the surgeon [15], 2) there is a low content of periprostatic fat in these region, making it easier to get PSMs, and 3) surgical manipulation may cause ink to reach the tumor, leading to a false PSMs [16]. On the contrary, it has also been reported that the posterior or postero-lateral region is the most common PSMs site after RARP [16]. Some series suggest that biochemical recurrence was independent of PSMs location [17,18]. Furthermore, it has been reported that PSMs located in the posterolateral region are associated with worse prognosis [19].   being able to establish an association with PSMs, we will have to do a long-term follow-up to assess the behavior of BR in these patients.
Studies that directly compare the effect of PSMs with metastasis-free survival and mortality are less conclusive. One of the largest studies, out of a registry of 65,633 patients, demonstrated a significant effect of PSMs on cancer-specific mortality (OR: 1,70, [1.32-2.18]) [21].
It seems that experience and careful attention to the surgical procedure also play an important role in decreasing the incidence of PSMs. Sooriakumaran P, et al. [22] reported a significant correlation between surgeon's experience and PSMs rate [22]. Ahlering TE, et al. [23] also reported a significant improvement in the PSMs rate associated with extensive surgical experience [23].
Limitations of the present study include its retrospective nature and the relatively small sample size. Furthermore, clinical examinations and surgical samples assessment were not performed by the same clinicians or pathologists. However, the initial experience of our urology department is reported.

Conclusions
It is important to consider preoperative PSA as a predictive factor for PSMs and correlate it with the pathologic result of the surgical specimen, these should guide treatment election and the necessity for closer postoperative follow-up.
Prospective studies with larger sample size should be encouraged. Furthermore, because the RARP learning curve may differ by surgeon, studies involving multiple surgeons are still necessary.