Laparoscopic radical prostatectomy (LRP) is an established minimally invasive procedure for the treatment of prostate cancer. It is associated with a shorter hospital stay and less postoperative pain than the open approach [1,2]. Although laparoscopy is minimally invasive, it is associated with postoperative pain primarily at the trocar and extraction wound sites, with the highest degree of pain occurring on the first postoperative day [3].

Currently, postoperative analgesic treatment principles are directed towards facilitating early postoperative mobilization and enhanced recovery. These are achieved through multimodal analgesic strategies based on the concurrent use of primarily non-opioid analgesics, which can have additive, if not synergistic, effects that produce superior analgesia, thereby decreasing opioid use and opioid-related side effects. These strategies frequently involve the use of different regional anesthesia techniques, with a preference for minimally invasive approaches over more aggressive anesthetic approaches to avoid possible complications [4,5].

Transversus abdominis plane (TAP) blockade and surgical wound infiltration (WI) are two common regional techniques used in multimodal analgesia that provide pain relief and reduce opioid consumption in a variety of surgical procedures [6-8]. TAP blocks neural afferents from the anterolateral abdominal wall (T6 to L1) by injecting a local anesthetic into the transversus abdominis fascial plane under ultrasound guidance or anatomical landmarks [6]. Although safe and effective, complications related to TAP such as nerve or vascular injuries have been reported [9-11], and the technique requires training and experience, is operator-dependent, and preferably performed under ultrasound guidance, leading to increased cost and resources. Furthermore, previous studies reported an average procedure time of 10 min [12], which might be problematic in the absence of parallel-processing space for regional anesthetic procedures [13]. In comparison, surgical WI with local anesthetics is a simple, safe, and low-cost technique for postoperative analgesia, which may provide an equally effective analgesia in the correct setting [14].

Several studies have compared the effectiveness of WI and TAP in different urologic [15], colonic [7,16], and gastrointestinal laparoscopic procedures [17], but no prospective comparative data are available for LRP.

Our hypothesis was that pre-incisional subcutaneous WI could be an alternative to TAP blockade for acute pain management in LRP as part of a multimodal analgesic approach, providing adequate analgesia and promoting enhanced recovery.

The aim of this prospective, double-blind, randomized controlled clinical trial was to compare the analgesic efficacy of WI and TAP in the first 48 h after LRP by analyzing numeric rate scale (NRS) values and opioid consumption.

This was a single-center, prospective, controlled, double-blinded randomized trial with two parallel arms performed between September 7, 2020 and June 19, 2022. The study protocol was registered at EudraCT.gov (Identifier number: 2019-004089-16) on October 14, 2019 and approved by the Institutional Review Board committee (approval number 15/19) on April 30, 2020. This study was conducted in accordance with the principles of the Declaration of Helsinki. The results are reported according to the current consolidated standards of reporting trials guidelines.

From September 2020 to June 2022, 67 patients were assessed for eligibility, of which seven were not enrolled on the basis of exclusion criteria or refusal. Sixty patients were enrolled in the trial and were randomized. Two patients were excluded after being allocated to the WI group because of conversion to open surgery. The remaining 58 patients were analyzed (Fig. 1).

Baseline characteristics were similar in both groups except for diabetes, which was more common in the WI group (P = 0.038), and age, which was lower in TAP patients (P = 0.031). The patient characteristics are summarized in Table 1.

The details of intraoperative hemodynamic management, surgical features, and lengths of surgery are presented in Table 2. No hypotensive events were observed during the surgery. No patient experienced complications related to regional analgesia, and there were no intraoperative events attributable to the systemic effects of local anesthetics in either group.

Median NRS values registered at rest and during cough/movement during the immediate postoperative period in PACU (0-4 h period; at rest: at 1 h P = 0.844; at 2 h P = 0.736, at 3 h P = 0.700; at 4 h P = 0.971; during cough: 1 h P = 0.698; at 2 h P = 0.834, at 3 h P = 0.922; at 4 h P = 0.618) and on the hospitalization ward (6-48 h period; at rest: 6 h P = 0.816; at 12 h P = 0.395, at 18 h P = 0.472; at 24 h P = 0.812, at 36 h P = 0.358, at 48 h P = 0.397; during cough: 6 h P = 0.974; at 12 h P = 0.712, at 18 h P = 0.691; at 24 h P = 0.708, at 36 h P = 0.572, at 48 h P = 0.929) did not show statistically significant differences and are shown in Figs. 2 and 3 respectively.

We performed an exploratory analysis of the opioid requirements. There were no statistical differences in the postoperative MME requirements in the TAP and WI groups during the entire 48-h period (1.7 ± 3.1 vs. 1.8 ± 4.1 mg; P = 0.914) or when analyzing the early (0-4 h) and late (4-48 h) periods separately (TAP, 1.6 ± 2.9 mg vs. WI, 1.1 ± 1.8 mg for the early period and TAP, 0.1 ± 0.5 mg vs. WI, 0.6 ± 3 mg for the late period).

There were no postoperative complications related to the TAP or WI technique or complications associated with the systemic effects of the local anesthetic in any of the patients.

The difference in the incidence of overall complications between the two groups was not statistically significant (P = 1.000). In the TAP group, a case of ureteral fistula required surgical reintervention, a case of bladder perforation was managed conservatively, and a case of obturator nerve injury required rehabilitation. In the WI group, cases of bladder perforation and hemorrhage did not require surgical intervention. PONV was very rare in both groups, and only one patient in the TAP group experienced PONV.

Results of the linear regression analysis showed that mean NRS values at the 48 hours postoperatively were independently associated with total opioid requirements (95% CI, 0.49 [0.03-0.09]; P < 0.001), while surgery duration (P = 0.698), age (P = 0.383), lymphadenectomy (P = 0.895), surgical postoperative complications (P = 0.432) and diabetes mellitus (P = 0.844) were not independently associated.

Neither of the secondary outcomes presented significant differences between the 2 groups (Table 3).

Effective pain management is key for optimal postoperative recovery and an essential component of enhanced recovery protocols [20]. However, direct high-level evidence is often lacking to support an optimal approach, even in commonly performed procedures, such as laparoscopic prostatectomy. The current study is the first prospective randomized trial comparing two regional analgesic approaches coupled with non-opioid-based multimodal analgesia for LRP. The results of this study did not show benefits of either locoregional technique modality for acute pain management in LRP, while showing excellent pain scores when these techniques were applied as part of a standardized non-opioid-based multimodal regimen.

The choice of an ideal pain management strategy should be based not only on its safety and efficacy, but also on the ease of administration and cost. From this perspective, although WI showed no differences in terms of pain control compared with TAP, WI could be considered more advantageous because it is less time-consuming and not dependent on the availability of ultrasound equipment or specially trained personnel, and complications after WI are rare [21].

In our study, both analgesic strategies provided excellent pain control, with mean NRS values < 2 in the first 48 h, both at rest and during movement. Our results were in accordance with those of studies on other types of surgeries, such as laparoscopic colectomy [7,16], where similar levels of pain control were observed for WI and TAP. In those studies, although no differences were observed between the two techniques, similar to the results of our study, the recorded pain intensity was generally higher than our data. This could be due to the timing of the regional anesthesia administration, which was pre-incisional in our study, which could influence the effectiveness of postoperative analgesia by blocking sensory flow in the periphery before the creation of the painful stimulus [22,23], or the intrinsic differences in the type of procedure (extraperitoneal vs. intraperitoneal LRP); however, a study that compared both approaches of LRP showed that narcotic analgesic requirements were similar [24].

Another important aspect of our study was the multimodal analgesic regimen that accompanied both types of regional anesthesia. We used a standardized hospital protocol based on scheduled administration of paracetamol, NSAIDS, and metamizole, because several studies have demonstrated decreased opioid use with this approach [5,25]. In fact, we observed that opioid requirements were not only similar between the groups but were also extremely low. The results of other studies which compared WI and TAP in laparoscopic surgery also showed similar opioid requirements between the two groups; however, the average consumption was significantly higher in both groups [16-18]. This may be due to the fact that the multimodal analgesic regimen we used relied on non-opioid agents that may have synergistic effects and allow the administration of regularly scheduled rather than as-needed doses. Minimizing the use of postoperative opioids is a major advantage for controlling the effect of medical practices on the opioid epidemic and minimizing opioid-related side effects, such as PONV.

Our study had some limitations. Abdominal wall sensitivity tests were not performed to assess TAP blocks because they were performed after the start of general anesthesia. However, it is well known that the extent of sensory blockade may not necessarily reflect the analgesic effect of the TAP block [26], and we did not observe intraoperative hypertensive episodes, which might occur due to inadequate analgesia [27]. Another potential limitation was that an unblinded surgeon could have affected postoperative patient care. Furthermore, we did not include a control group (without a block) because both techniques had been shown to provide better analgesic effects than a placebo [28].

In conclusion, the results of our prospective trial indicate that WI is not superior to TAP in achieving pain control during the first 48 h after LRP when combined with a non-opioid-based multimodal pain management strategy. Arguably, given that the pain scores and opioid requirements were very low in both groups, it is likely that the modalities were equally efficient, although this clinical trial was not designed to assess this hypothesis directly.