Outcomes of Minimally Invasive Radical Prostatectomy–a Contemporary Review

Abstract

Prostatectomy has been widely accepted as a treatment option for prostate cancer and can be performed via an open, laparoscopic, and robotic approach. The outcomes following prostatectomy are primarily sub-grouped into oncological and functional outcomes. Oncological outcomes have been comparable in the above three surgical modalities. However, the robotic platform seems to have a better functional outcome compared to open prostatectomy. The data on the outcome of the laparoscopic approach is scarce and is not widely performed due to technical difficulty. With experience continence outcomes have reached a plateau in many robotic series, however, the potency outcome is the real Achilles tendon of this procedure. Many factors influence potency outcomes but the amount and quality of nerve-sparing is one factor that is under a surgeon’s control and it improves with experience.

Introduction

A better understanding of the periprostatic anatomy especially the dorsal venous complex (DVC), neurovascular bundle, and the striated urethral sphincter led to the refinement of radical prostatectomy (RP) techniques [1–3]. As the surgeons became more equipped with minimally invasive techniques, prostatectomy was attempted using laparoscopic techniques in 1997. Though the oncological outcomes were comparable with open prostatectomy, due to the length of surgical procedure and length of postoperative hospital stay, laparoscopic radical prostatectomy (LRP) was not popular [4].

With the introduction of computer-assisted surgical devices with robotic arms like the da Vinci robotic systems, prostatectomy has now been increasingly performed using this device. The vision of a magnified 3D image and use of wristed instruments allowed novice surgeon to perform this procedure safely with comparable results to an experienced surgeon. Simultaneously, with the improvement in laparoscopic instruments and HD systems, interest in LRP has increased especially in Europe [5, 6]. In this article, we have reviewed the outcomes following RP using minimally invasive techniques.

Materials and Methods

Terms like “outcomes”, “radical prostatectomy”, “continence rates”, “potency”, “minimally invasive prostatectomy”, “robotic prostatectomy”, and “Robot-assisted radical prostatectomy” have been used to do literature search using PUBMED and Google scholar. Articles primarily after 2008 were selected along with other significant studies that were used here in this study.

Minimally Invasive Radical Prostatectomy

Both LRP and robotic-assisted radical prostatectomy (RALP) have the same indication as radical retropubic prostatectomy (RRP) in the management of prostate cancer. It is traditionally recommended for a localized carcinoma prostate (CaP) (T1, T2) and resectable locally advanced CaP. Bleeding diatheses and the inability to sustain general anesthesia due to high cardiac risk are the only absolute contraindication of minimally invasive RP. Previous abdominal surgeries, presence of intrabdominal grafts like mesh, previous pelvic surgery, presence of stomas, morbidly obese patients, prior radiotherapy, and prior transurethral resection of the prostate can be challenging and considered as a relative contraindication for minimally invasive prostatectomy.

Laparoscopic Radical Prostatectomy

Although laparoscopic radical prostatectomy (LRP) is advocated as having less bleeding, better optics, less pain, shorter duration of stay in the hospital, it is the most challenging modality to be used to perform prostatectomy and the most difficult skill set is laparoscopic suturing especially the location of the urethra in the pelvis that makes the anastomosis difficult [7]. Also, LRP is associated with increased emergency visits, hospital readmission, and increased reoperation rates [8]. In the hands of an expert surgeon, the continence rates and anastomotic stricture rates are like open prostatectomy. Early rates of positive surgical margins (PSMs) were higher with LRP but long-term cancer control outcomes are still unknown [9].

Robot-assisted laparoscopic prostatectomy

The majority of the radical prostatectomies in the US are now being done using the DA Vinci system and it is highly popular due to technical ease for the surgeon, especially during the vesicourethral anastomosis especially even by novice surgeons as its learning curve is fairly facile [10]. It also has all the advantages of LRP [11]. Similar PSMs have been reported using this technique; however, long-term cancer control data is awaited [12]. Many reports have been published now reporting feasibility and safety of the Da Vinci SP system, which is a single port robotic system [13, 14]. RALP had lower blood loss/transfusion rate with better functional outcomes compared to LRP [15]. In a systematic review and meta-analysis, RALP provides same oncological outcomes but continence and potency were better in RALP compared to open RP/ LRP [16]. However, randomized control trial comparing all three modalities are unavailable and long term RALP are still awaited.

Influence of Intraperitoneal Vs Extraperitoneal Approaches

The transperitoneal approach is the most common approach to LRP and RALP and is favored by most surgeons due to familiarity with anatomy. However, the extraperitoneal approach involves an extra skillset of creation of extraperitoneal space using a balloon dilator device and the surgeon must work in restricted space. Many studies have been performed comparing extraperitoneal vs transperitoneal LRP and found that the operative times and perioperative outcomes were similar [17–19]. With the extraperitoneal approach, peritoneum acts as a natural barrier thus minimizing bowel injury, and if a leak occurs, it is confined to extraperitoneal space.

Immediate Intraoperative and Postoperative Outcomes

Studies with one to one comparison between RRP and minimally invasive techniques are rare and mostly retrospective observational studies. In randomized controlled study by Guazzoni et al. comparing LRP vs RRP, LRP had lower blood loss and transfusion rates [20]. RALP did not show any advantage over LRP in the peri and immediate postoperative outcomes in randomized controlled trials done in two different centers, but had better post-operative continence, potency outcomes, and easier learning curve [21, 22].

Intraoperative Complications

Patient Positioning

Transient lower limb neuropathies due to steep Trendelenburg positioning have been described and can occur in about 1.3% of patients undergoing prostatectomy and are due to extreme hyperextension of the hip leading to transient sensory and motor neuropathy. There is a chance of an increase in intraocular pressure in steep Trendelenburg position [23].

Intraoperative Injuries

Rare complications like bowel injury and vascular injury can occur during the placement of trocars and have been reported occasionally. The key aspect of management includes providing tamponade and meticulous repair of the injury. Minor injuries can be repaired minimally invasively, while major complex injury merits conversion to open technique. Open conversion is again rare and is reported to be about less than 2% more in surgeon’s early experience [24]. Rectal injury is again rare and has been reported to be up to 2.4% [25]. They usually occur during apical dissection and the best way to manage is to identify the injury and correct it intraoperatively.

The transfusion rate following minimally invasive prostatectomy has been reported to be less than 2% and this is probably due to the tamponade effect of the pneumoperitoneum reducing venous bleeding [26]. Vascular injuries can also occur during pelvic lymph node dissection (PLND) and are reported to be about 1% following PLND. Rarely obturator nerve injury may occur which needs to be repaired primarily [27]. Ureteral injury is rare and can occur while PLND during posterior first approach to RALP.

Immediate Postoperative Complications

The incidence of DVT has been reported to be as low as 0.5% after LRP and RALP [28]. This seems to be a definite advantage over RRP as the patient can ambulate early, thus reducing venous stasis and thromboembolism. The incidence of prolonged postoperative ileus has been described to be less than 1% and is managed conservatively [29]. Enhanced recovery after surgery protocol has now been widely followed especially in Europe and the US, minimizing the risk of post-operative ileus [30–32]. Postoperative intra-abdominal hematoma is rare and is usually due to venous bleed. This can be controlled by traction after inflating the Foley balloon. Inspecting the pelvis for any bleeding following the exsufflation of the pneumoperitoneum during the procedure can prevent this complication. Rarely, there can be leakage of urine from the anastomosis leading to the formation of urinoma [29]. This can be prevented by performing a watertight anastomosis and the use of the robotic platform has helped in achieving this effectively. This is managed conservatively by retaining the urinary catheter. Rarely, they are managed by placing a percutaneous catheter. A urinary leak can lead to urinary strictures.

Outcomes Described

Oncological Outcomes

The procedure aims to achieve cancer control. Organ confined disease with negative surgical margins, absence of an extracapsular extension, absence of seminal vesical invasion, absence of biochemical recurrence/PSA persistence, lack of local progression, lack of metastases, cancer-specific survival, and overall survival are the ideal outcomes following surgery. Independent factors determining cancer control include Gleason score, TNM staging of disease, PSA doubling time, and time to BCR. In a high-volume centre, long-term follow-up to 5 years showed that RALP is oncologically effective procedure [33]. In a systematic review, PSM rate is similar in RALP, RRP, and LRP; however, long-term outcome comparison is still unavailable. [12]

Functional Outcomes

Continence Outcomes

Urinary incontinence following RP is due to intrinsic sphincter deficiency. There is a 4 to 31% risk of long-term incontinence following RP [34]. Long-term incontinence is usually multifactorial which includes preoperative characteristics like age, higher BMI, presence of comorbidities, large prostate, and severe LUTS along with intraoperative factors like surgeon experience; the surgical technique is correlated with a higher risk of urinary continence. Surgical technique is one of the most important factors and is one factor that can be controlled by the surgeon [34].

With better optics, better visualization of the prostatic apex is possible, and with precise dissection, using minimally invasive techniques helps in achieving tension-free watertight anastomosis with minimal trauma to periurethral tissue. Apart from these advantages, minimally invasive techniques have allowed surgeons to experiment and develop innovative technique. Sparing of puboprostatic ligaments, preservation of bladder neck, site of DVC division, anterior suspension of urethrovesical anastomosis, nerve-sparing degree, reconstruction of posterior musculofascial layer, complete periprostatic anatomy preservation, and retzius sparing approaches [34–38]. Perineal RARP has shown to have better continence compared to RALP; however, it may not be applicable in locally advanced tumor [39]. Preserving the anatomical support around the apex of the prostate helps in maintaining the continence, and this is the basis of most of the modifications described during prostatectomy. There also have been attempts to reconstruct the periurethral support like advanced reconstruction of vesicourethral support (ARVUS) wherein the fibers of the levator ani muscle, Denonvilliers fascia, retrotrigonal layer, and median dorsal raphe were used to form the dorsal support for the urethrovesical anastomosis. This procedure had better and earlier continence compared to just posterior reconstruction [40]. Techniques that aim at preserving the tissues like puboprostatic ligament, lateral prostatic fascia, and endopelvic fascia around the apex help in early postoperative continence recovery [41, 42]. Post-operative pelvic floor rehabilitation therapy’s role in post-operative continence cannot be undermined and is an effective way for continence recovery [43].

Outcomes of continence have been measured differently in prostatectomy literature. Most commonly used is the number of pads used which again is vague. A standardized measurement based on the number of pad usage has been described [44]. Twenty four-hour pad weight test has been used to study continence [43]. A validated questionnaire like EPIC score has also been used to measure continence. In his systematic analysis, Ficarra et al. have recommended the use of pads as a measurement of continence [34].

Potency Outcomes

The best potency rate reported that post-RALP was 94% in low-risk organ-confined prostate cancer [45, 46]. The outcomes of potency without intervention have not changed in the last 17 years [47]. A recent meta-analysis showed that patient undergoing RALP had better potency than retropubic radical prostatectomy [48]. The LAPPRO data showed better potency with RALP when compared to radical retropubic prostatectomy in low to intermediate risk and the reverse with high-risk group. Also, the same data showed a correlation between the nerve-sparing and cumulative potency recovery [49].

Age, ethnicity, preoperative PSA, preoperative sexual function, hypertension, diabetes, and institute were significant factors that were found to be linked to post-operative sexual function irrespective of treatment provided [50–52]. The potency is consistently linked to the age of patients. Increasing age has been shown to be associated with a drop-in potency. This trend persisted even irrespective of the amount of nerve-sparing. In a large series of patients undergoing RARP, potency was lower in patients above 70 years in a similar subgroup of younger patients (33.5% vs. 52.3%, respectively) [53]. This has been shown even in open radical prostatectomies too [54]. One of the important factors that determine the potency outcomes following prostatectomy is preoperative erectile function status. Various tools have been used to assess preoperative potency. SHIM score has been used widely in preoperative erectile function assessment and the timing of the SHIM score assessment has been assessed. SHIM score assessment before the biopsy is a better indicator of baseline sexual function versus doing it at any other time in the course of treatment [55]. Nomograms to assess post-operative potency at various time points after prostatectomy take into consideration many preoperative and intraoperative factors [56, 57].

With improved understanding of periprostatic anatomy and the description of cavernosal nerve and with the help of minimally invasive techniques, surgeons have been innovative in exploring various techniques of nerve-sparing. Traditionally, the nerve-sparing techniques have been described based on the planes of dissection like intrafascial, interfascial, and extrafascial dissection. Using robotic surgery, different levels of nerve-sparing have been described by an expert surgeon. A 5-point grading system was proposed by Schatloff et al. that correlated to the quantity of residual nerve spared. Tewari et al. suggested a grading system based on anatomical landmarks into a 4 point system. A total of 90.6, 76.2, 60.5, and 57.1%, respectively, were the potency rates following RARP, while using this grading system for grades 1, 2, 3, and 4 in preoperatively potent patients. Irrespective of the different grades of nerve-sparing described, all the studies suggest more the nerves spared more the chance of potency recovery. The CEASAR study, in their conclusion, found that bilateral nerve-sparing (BLNS) prostatectomy offered most benefit in a patient who was preoperatively potent but also concluded that it should still be offered to patients with low baseline sexual function [58]. The safety of nerve-sparing has been debated in high-risk disease and various nomograms have been used to predict the extracapsular extension like the PRECE scores that help in surgeon balancing the nerves paring while maintaining oncological principles [59]. However, nerve-sparing has been proven safe even in high-risk tumors [60]. Neurovascular structure-adjacent frozen-section examination (NeuroSAFE) technique was first developed by Martini Klinik, Germany, that utilizes intraoperative frozen section to balance NS during RALP [61]. In large prospective study, it was found that NeuroSAFE could be used to offer NS in high-risk patients, while reducing PSM, thus improving potency at 12 months [62].

Many preoperative risk criteria have been proposed to select patients who will benefit the most following a nerve-sparing prostatectomy in terms of potency recovery, simultaneously keeping the PSM low [63–65]. These took into consideration various other factors like the Charlson comorbidity score (CCI), which has been used as a tool to indicate the general health status patients. Patients with low CCI did better when compared to patients with high CCI [66].

The post-operative potency measurement suffers from a lack of standard definition. Studies have used the ability to perform intercourse following surgery that have been used as a measure of potency. While there are studies that used validated questionnaires like ESI or SHIM score, they again suffered from various cut-offs used [67]. Also, the use of vacuum erection device (VED) and PDE-5 inhibitors in the post-operative penile rehabilitation has shown increased erectile function [68].

Trifecta Outcomes

The term trifecta for RP was used by the team from Memorial Sloan Kettering Cancer Centre in 2005 for outcomes following RP and includes achievement of potency, continence, and absence of biochemical recurrence. Since its description, various studies have used this as a measure to describe outcomes following prostatectomy. However, the definition of individual components suffered from standardized definition leading to notable variations in its definition [69]. Patel et al. described an ideal cohort of young patients with localized prostate cancer with a full nerve-sparing prostatectomy; the trifecta rate was 83.1%, while other studies have shown rates of 57% to 62% following nerve-sparing prostatectomy [70–72].

Pentafecta Outcomes

Following the description of the trifecta, Patel et al. felt that this did not adequately represent patient outcomes as it did not consider the intraoperative and postoperative complications. It also did not consider the mental status of the patient if he had a PSM. Hence, they proposed “Pentafecta” as a new measure of outcome following surgery that included lack of intraoperative complications and the absence of PSM [70]. In the original paper, pentafecta rate was 70.8% at 12 months in patients with localized prostate cancer and full nerve-sparing prostatectomy [70]. Though the “Pentafecta” was initially used in RALP, it has been used in series describing LRP as well with pentafecta rates ranging from 27.5 to 72.9% in BLNS LRP though originally described in RALP now has been used by surgeons who implement other approaches [73–80]. The main reasons for not achieving pentafecta have been linked to lack of potency followed by PSM, except in a series where potency followed by lack of continence prevented pentafecta outcomes [73, 75, 81, 82].

Post-operative Lymphocele

Lymphoceles are most commonly linked to PLND with RALP [83–86]. They are usually symptomless and are undetected in a lot of patients; thus, the actual rates of lymphoceles are unknown. Solberg et al. reported the incidence of lymphocele in RRP as 61% and laparoscopic prostatectomy as 37% [85]. The incidence rates following RALP are between 9 and 51% [87, 88]. The incidence of clinically significant lymphocele (CSL) varies from 0.4 to 16% [89]. Fever, pain in the abdomen, pain in the lower limb, leg swelling, frequent urination, thrombosis of lower limb, and infections are the symptoms associated with CSL [83, 90, 91]. A total of 1.3 to 2.5% is the incidence of lymphocele that needed drainage [83, 91]. The extent of lymph node dissection and the number of nodes sampled have been the two most consistently linked factors to clinically significant lymphocele.

Increased continence, potency, and non-inferior oncological outcomes following RALP were seen in systematic reviews [12, 34, 92]. Also, in a meta-analysis, better potency rates were reported in patients undergoing RALP vs RRP [22]. Ultimately, the goal of the surgical technique should be to perform optimal nerve-sparing while keeping the margins clear. Also, it is important to educate the patient considering their preoperative factors and counsel them about the realistic expectations of outcomes of minimally invasive surgery.

Salvage Robot-Assisted Radical prostatectomy

About 27% of patients opt for primary non-surgical local treatment like radiation, cryotherapy, HIFU, etc. for prostate cancer [93]. In cases of recurrent cancer following primary local treatments, treatment options are minimal. These patients are either subjected to systemic androgen deprivation therapy or salvage radical prostatectomy (sRP) [94]. Originally, described as an open procedure with dismal outcomes in terms of high complication rates and poor functional outcomes. Currently, sRALP is being performed using DA Vinci system. Tough its safety and feasibility have been established, the outcome data is still in its infancy [95, 96]. Recently, in a multi-institutional comparison between open vs robotic sRP, it was found that more unilateral and BLNS was performed in robotic cohort vs open. The open group had shorter operative time (214 min vs 228 min, p < 0.001), longer hospital stay (5.6 days vs 2.9 days, p < 0.001), and higher blood loss (715 mL vs 222 mL, p < 0.01). Similar postoperative complication rates. The continence rates at 6 (22.2% vs 26.1%, p = 0.0234) and 12 (22.5% vs 32.1%, p = 0.043) months were statistically better in robotic group vs open group. The EF was similar at 6 months but statistically significant in the robotic vs open sub group (p = 0.03) at 12 months [97]. The key recommendation of this study was that this must be performed in high-volume centers. Onol et al. compared the outcome of sRALP in patients who underwent radiation vs focal ablative therapies and found that radiation group had inferior functional outcomes following sRALP, while focal therapies were associated with higher non organ confined disease and PSM rates; however, there was no significant difference in short-term BCR-free survival [98].

Conclusion

Minimally invasive RP is safe and effective in the hands of an expert surgeon in achieving trifecta in patients with localized prostate cancer and BLNS approaches should be offered when possible as it offers the best chance of achieving post-operative potency. The modality of surgery may not affect oncological outcome; however, potency outcome depends on quality of nerve sparing, which depending on the experience maybe better using robotic system compared to open/laparoscopic RP.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.