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  • Systematic Review
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21 August 2025

Postoperative Pain Following Gynecology Oncological Surgery: A Systematic Review by Tumor Site

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Division of Surgery and Cancer, Imperial College London, London W12 0NN, UK
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Department of Gynaecology Oncology, Imperial College Healthcare NHS Trust, London W12 0HS, UK
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Department of Gynaecology, Chelsea and Westminster Hospital NHS Foundation Trust, London SW10 9NH, UK
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Department of Anaesthetics, Imperial College Healthcare NHS Trust, London W2 1NY, UK
Cancers2025, 17(16), 2718;https://doi.org/10.3390/cancers17162718
This article belongs to the Section Cancer Survivorship and Quality of Life
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Simple Summary

Effective pain control after surgery for gynecological cancers is vital for patient recovery, yet current practices vary widely across different healthcare settings. This study reviewed and analyzed existing research to understand how pain is currently managed after these surgeries and to identify the most effective approaches. By examining 46 clinical trials involving over 5000 patients, the authors found that no single method worked best for everyone, but using a combination of treatments tended to improve pain control. The study highlights the need for clear and consistent guidelines to ensure all patients receive the most effective and personalized care after surgery. These findings aim to guide future research and support healthcare professionals in improving pain management for women undergoing gynecological cancer surgery.

Abstract

Introduction: Postoperative pain management is complex and crucial in major gynecology oncological surgery. Currently, there is no well-defined standardized approach, resulting in significant variability in practices worldwide. This systematic review evaluates the effectiveness of analgesic strategies used postoperatively in gynecological cancer surgery. Methods: A systematic review was conducted from inception to June 26th 2024 to identify all randomized controlled trials (RCTs) assessing pain management following any surgery for gynecological cancer. This was performed on the CENTRAL, PubMed, Embase, and MEDLINE databases. Results: A total of 46 RCTs met the inclusion criteria. Of these 5316 patients, 1844 patients had cervical cancer, 99 had endometrial cancer, and 158 had ovarian cancer. The remaining 3215 participants had unspecified gynecological cancers or benign pathology. No studies focused on postoperative analgesia for vulval cancer. A meta-analysis was not feasible due to heterogeneity in study design, analgesic interventions (i.e., opioids, local anesthetics, paracetamol, NSAIDs, and holistic and complementary therapies), and multiple routes of administration (i.e., oral, parenteral, regional, neuraxial, local infiltration, intraperitoneal, intramuscular, patient-controlled, topical, and rectal). No single analgesic modality demonstrated clear superiority. The median Jadad score for methodological quality of the included trials was 4. Conclusions: The limited cancer-specific RCTs and diversity of analgesia modalities utilized reflect the wide range of applications. Postoperative pain is multifactorial and cannot be adequately managed with a single agent. National and international guidelines should aim to establish a standardized framework for postoperative pain management in gynecological cancers, ensuring accessible, evidence-based care that enhances both short- and long-term patient quality of life.

1. Introduction

Postoperative analgesic management has evolved significantly over recent decades, with advances in the perception, definition, and measurement of surgery-related pain. Despite this progress, there is a lack of well-defined, standardized protocols tailored to specific surgery and cancer types. This variability results in suboptimal pain control, adversely impacting short- and long-term patients’ quality of life following major gynecology oncological surgery [1,2,3,4].
Poorly controlled postoperative pain is an independent risk factor for reduced patient satisfaction, prolonged recovery, higher readmission rates, development of chronic pain with increased overall surgical morbidity and mortality [5]. Effective postoperative pain management is crucial in patient recovery. However, uncontrolled postoperative pain remains a major problem affecting 85% of patients [6]. While numerous analgesic options exist and understanding of pain pathophysiology and perception has improved, there is no universally agreed pain management approach.
There has been great advancements underpinning the management of pain, utilizing different treatment modalities targeting specific aspects of the pain signaling pathway [7]. Numerous studies have demonstrated the effectiveness of a multimodal approach, combining systemic with regional analgesic techniques to reduce long-term opioid requirements [8]. The purpose of this systematic review is to evaluate these various analgesic options in their effectiveness according to tumor site.

2. Materials and Methods

2.1. Search Strategy

The systematic search followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This protocol was not registered in PROSPERO, as it was still under refinement during the initial phases of the study, and the decision was made to proceed without formal registration.

2.2. Literature Search

A comprehensive literature search was performed in the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, and MEDLINE databases for articles published from inception until 26 June 2024. The search strategy combined controlled vocabulary terms (e.g., MeSH) and keywords related to postoperative pain management (e.g., “analgesia,” “postoperative pain,” “pain relief”) and gynecological cancers (e.g., “ovarian cancer,” “cervical neoplasms,” “endometrial carcinoma,” “vulvar neoplasms”). Boolean operators and proximity searches were employed to enhance sensitivity and specificity. The detailed search strategies for each database are provided in Supplementary Material S1. Searches were limited to English-language publications.

2.3. Study Selection

All randomized controlled trials (RCT) investigating postoperative pain management following surgical treatment for gynecological cancers (cervical, endometrial, ovarian or vulval) were included. Eligible studies were required to assess pain severity using standardized and validated scoring systems, such as the Visual Analog Scale (VAS), Numeric Rating Scale (NRS), or comparable tools, which provide quantifiable measures of patient-reported pain.
Studies involving participants undergoing medical or radiological treatments for management of gynecological cancers were not included. Additional exclusion criteria included conference abstracts, commentaries, study protocols, non-randomized designs, preclinical research, secondary analyses of data from prior randomized controlled trials, and studies not published in English.

2.4. Data Extraction and Quality Assessment

Following removal of duplicate records, two independent reviewers (SC and HS) screened 6850 titles and abstracts, followed by full-text assessment for eligibility. Disagreements regarding study inclusion were resolved through consensus and when necessary, were adjudicated by a third reviewer (SS). An overview of the search results and screening process is summarized in the PRISMA flow diagram (Figure 1).
Figure 1. PRISMA flowchart of included studies.
Data extraction was conducted using a pre-tested form within the Covidence platform (Covidence, Melbourne, Australia). The first author (SC) performed the initial data extraction for each included study, which was subsequently reviewed and verified by the second author (HS). Extracted data included publication year, country of origin, sample size, type of intervention, primary and secondary outcomes along with their corresponding measures, duration of follow-up, journal of publication, journal impact factor, and any reported commercial funding. Table 1 summarizes the main characteristics of the studies.
Table 1. Summary of the included randomized control trials.
Two reviewers (SC and HS) independently assessed study methodological quality using the Jadad score and the Cochrane Collaboration’s risk of bias tool [54,55]. Where there were disagreements between reviewers, consensus was obtained after discussion with a third reviewer (SS).

2.5. Data Analysis

Data were analyzed according to tumor site. Studies that included participants with different types of gynecological cancers (e.g., ovarian, cervical, endometrial, cervical) but did not differentiate between pain analysis according to specific cancer types were categorized as generic cancers. RCTs that analyzed both benign and malignant gynecological surgical procedures, without reporting separate outcomes between the benign and malignant cases, were defined as generic (benign and cancer).
Authors were contacted in an attempt to attain data for tumor site-specific gynecological cancers in the studies that combined gynecological cancers with benign conditions. If site-specific data could not be provided, these studies were kept in the generic categories for analysis.
Statistical analysis was performed using SPSS version 25.0 (IBM, Armonk, NY, USA), with the median and interquartile ranges (IQR) used to summarize continuous non-parametric variables. Inter-rater reliability for study screening was assessed using Cohen’s kappa statistic to evaluate the level of agreement between reviewers.
Substantial clinical and methodological heterogeneity was observed across the included studies, including variability in patient populations, surgical procedures, intervention types, outcome measures, and timing of postoperative pain assessments. Differences in pain measurement tools and follow-up durations further contributed to this heterogeneity, rendering quantitative meta-analysis inappropriate. Consequently, a qualitative synthesis was conducted to narratively summarize and interpret the findings, emphasizing common patterns and notable differences among studies.
In accordance with the journal’s guidelines, we will provide our data for independent analysis by a selected team by the Editorial Team for the purposes of additional data analysis or for the reproducibility of this study in other centers if such is requested.

3. Results

Following exclusion of 1113 duplicates, 6850 titles and abstracts were screened. Two hundred and sixty-eight full texts were assessed for eligibility. After a further exclusion of 222 full texts, 46 RCTs were included in this systematic review. Inter-rater reliability was evaluated using Cohen’s kappa statistic, yielding κ = 0.653 for title and abstract screening and κ = 0.821 for full-text screening, indicating substantial to strong agreement.
The included studies were published between 2000 and 2024 (median year: 2020). The included trials involved 5316 participants of which 1844 had cervical cancer, 99 had endometrial cancer, and 158 had ovarian cancer. The remaining 3215 participants were unspecified gynecological cancers or benign pathology (Figure 1).

3.1. Cancer Types

There were 29 trials which investigated postoperative analgesia in gynecology cancer-specific operations, of which 11 trials were cervical cancer [8,9,10,11,12,13,14,15,16,17,18], 1 trial was endometrial cancer [19], 4 trials were ovarian cancer [20,21,22,23] and 13 trials assessed multiple gynecological cancers [24,25,26,27,28,29,30,31,32,33,34,35,36]. Seventeen trials included both gynecological cancers and benign pathology [37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53]. There were no studies investigating postoperative analgesia use for vulval cancer (Table 2).
Table 2. Summary of pain scores categorized according to gynecological cancer type and pain score system used in each study.

3.2. Surgical Approach

Minimally invasive surgery (MIS) was analyzed in 11 trials (4 cervical; 1 endometrial; 2 generic cancer; 5 generic (benign and cancer) [8,13,15,17,19,34,35,37,39,42,51]. Seventeen trials reviewed open abdominal surgeries (1 cervical; 3 ovarian; 8 generic cancers; 5 generic (benign and cancer) [16,20,22,23,24,25,26,28,29,30,31,32,40,44,45,46,50]. Three trials assessed both minimally invasive surgery and open abdominal surgery (3 generic (benign and cancer) [38,48,52]. One study assessed the loop electrosurgical excision procedure (1 generic (benign and cancer) [41]. The surgical approach was not specified in 14 trials (6 cervical; 1 ovarian; 3 generic cancers; and 4 generic (benign and cancer)) [9,10,11,12,14,18,21,27,33,36,43,47,49,53].

3.3. Methods of Pain Assessment

Table 1 summarizes the included trials with the interventions investigated, methods of pain assessment, and monitoring duration interval. Thirty one trials used Visual Analog Scale (VAS) scores to assess pain [9,10,11,12,13,14,15,16,17,19,20,21,23,24,26,28,30,33,34,36,37,39,40,41,42,43,47,48,50,51,52], eleven trials used Numerical Rating Scale (NRS) [8,18,22,25,29,31,38,44,45,46,53], and four trials used other pain scales [27,32,35,49]. Seventeen trials were performed in China [8,9,10,11,12,13,14,15,16,17,18,19,34,35,38,42,47], five in USA [32,39,40,49,52], four in Turkey [33,36,41,43], and three in Egypt [20,24,46]. Two trials were performed in Germany [21,23], Iran [30,50], Japan [29,51], Sweden [22,44], and Thailand [26,37]. One trial was performed in Australia [28], Hong Kong [45], India [25], Italy [48], Republic of Korea [27], Poland [31], and Taiwan [53].

3.4. Types and Mode of Analgesia

Due to the heterogeneity of the trials, the results are presented in Table S2. Table 3 summarizes the types of analgesics and mode of administration in each study. The diversity across studies precluded meta-analysis and qualitative comparisons, highlighting the wide range of analgesic approaches, which limits generalizability.
Table 3. Summary of the type of analgesia and mode of delivery in each study.
Most studies (n = 37) included an opioid in at least one arm [8,9,12,13,15,16,17,19,21,22,23,25,26,27,28,29,30,31,32,33,34,36,37,38,39,40,42,43,44,45,46,47,49,50,51,52,53], while 23 studies involved non-steroidal anti-inflammatory drugs (NSAIDs) [8,9,12,13,16,19,26,27,28,31,33,35,36,37,39,40,42,44,45,47,49,51,52]. Seventeen trials utilized local anesthetics [8,10,20,21,22,23,24,25,28,29,30,39,40,41,44,46,51], 10 studies used paracetamol [25,31,36,39,44,45,49,50,51,52], and 5 explored holistic and complementary therapies [11,32,35,37,45].
Three studies included dexmedetomidine [27,34,46], 1 assessed magnesium with local anesthetics in a TAP block [24], 3 addressed psychological and empathetic care [11,14,18], and 3 explored lifestyle measures (diet and exercise) [18,35,48]. Six studies examined other drugs, including Metamizole, Duloxetine, Gabapentin, Ketamine, Opioid receptor antagonists, and Naloxone [7,15,31,35,50,53], while 2 evaluated abdominal binders [26,35].
Thirty-five studies used parenteral analgesia [8,10,12,13,15,16,17,19,21,22,23,26,27,28,29,30,31,33,34,35,36,38,39,40,41,42,43,44,45,46,47,49,50,52,53], 25 included patient-controlled analgesia (PCA) [8,12,15,16,17,22,23,25,26,27,28,29,32,33,34,36,38,40,42,43,45,47,49,52,53], and 9 involved oral medications [11,26,37,39,44,48,49,50,52]. Regional anesthesia was used in 6 studies [10,16,20,24,29,39], local anesthesia in 12 [21,22,23,25,28,29,30,36,40,43,44,46], and other delivery methods such as intraperitoneal [22], intramuscular [34], topical [41], and rectal [31,51] were also investigated.

3.5. Cervical Cancer

Two studies assessed the impact of nursing interventions, which significantly reduced pain levels [14,18]. One study reported reduced pain levels at 6, 24, 48 and 72 h with a structured care model incorporating pain-specific training, psychological support, and enhanced medication compliance [14]. Another study showed that an empathetic care model, which included training in emotional support, communication techniques, and interdisciplinary collaboration, significantly improved pain management [18].
NSAIDs were also shown to decrease postoperative pain compared to control groups [8,9,12,13]. One study analyzed the effects of continuous infusion, bolus, and patient-controlled opioid delivery, finding that both continuous and patient-controlled time-scheduled decremental oxycodone regimens significantly reduced pain at 1, 6, and 48 h, with the latter group using a lower cumulative dose compared to the other groups [17].
Two RCTs demonstrated that regional anesthesia with local anesthetics was an effective analgesic approach. Specifically, ilioinguinal, iliohypogastric, and erector spinae plane blocks (ESPB) provided effective pain relief, while the transverse abdominis plane block (TAPB) showed minimal improvement [10,16]. Additionally, one study reviewed various doses of ketamine and its enantiomers, all of which significantly improved postoperative pain at 1, 2, and 3 days compared to controls [15].

3.6. Endometrial Cancer

One study compared remifentanil and propofol bolus injections prior to extubation, finding no significant difference in VAS scores. However, remifentanil was associated with a shorter PACU stay [19].

3.7. Ovarian Cancer

A RCT found that ESPB significantly reduced postoperative pain at 0–30 min, 2–4 h, and 18 h compared to TAPB, leading to reduced tramadol use for rescue analgesia [20]. Two studies compared different local anesthetics in neuraxial blockades showed no significant differences in pain relief [21,23]. Another study evaluated intraperitoneal local anesthetic versus control with no significant improvement in analgesic efficacy [22].

3.8. Generic Cancer

One study showed that dexmedetomidine infusion significantly reduced postoperative pain during activity at 1 h but had no effect at rest or at other time points compared to control [37]. Another RCT showed no significant difference in analgesic effects between IV PCA Dexmedetomidine and Fentanyl [34].
Four studies examined neuraxial anesthesia for postoperative pain management in gynecologic-oncologic surgery, showing mixed results. The mean pain severity during first ambulation was significantly lower in the patient controlled epidural analgesia (PCEA) group compared to the IV PCA group (p < 0.001) [30]. Pain scores at rest at 24 h and during coughing at 12 and 24 h were significantly lower in the epidural group than the parenteral opioid group, though VAS scores were similar between the parenteral lidocaine and epidural groups [36]. Another study found continuous rectus sheath block (CRBS) significantly superior to continuous epidural analgesia (CEA) at 24 h post-surgery [29] and adding patient-controlled to CEA provided no additional benefit in pain relief [25].
In pain management strategies, one study identified that Metamizole (without Ketoprofen) was inferior to acetaminophen when combined with Morphine on day 0 postoperatively. However, a multimodal approach (Morphine, Acetaminophen, and Ketoprofen, or Morphine, Metamizole, and Ketoprofen) provided equivalent analgesia, regardless of whether acetaminophen or metamizole was used [31].
Another study demonstrated the addition of magnesium to TAP blocks significantly improved postoperative pain at all time points apart from at 8 h [24]. Two studies compared parenteral NSAIDs (Tenoxicam, Ketoprofen) with placebo showed no significant difference in pain scores [28,33]. However, the cumulative PCA-Tramadol consumption was significantly lower in Ketoprofen treated patients (p < 0.05) [33].

3.9. Generic (Benign and Cancer)

Three studies evaluated the analgesic effects of opioids. One compared opioid use to a non-opioid regimen (Dexmedetomidine and Lidocaine), with the latter showing significantly lower pain scores [46]. Two others compared different parenteral opioids, yielding conflicting results regarding postoperative pain relief [39,42]. Another study assessed the addition of nalbuphine to an opioid-based PCA compared to opioid PCA alone showing no significant difference at any time points [52].
Two studies examined NSAIDs following gynecologic-oncologic surgery. One found significantly lower pain scores at rest and during movement in the Parecoxib group compared to controls, reflecting reduced PCA morphine use postoperatively [47]. In contrast, another study found no difference in analgesic outcomes between oral Celecoxib and IV Ketorolac [51].
One study showed the addition of Duloxetine to routine postoperative pain management significantly decreased pain compared to placebo at 2–48 h postoperatively [49].
Seven studies investigated the impact of the route of administration on postoperative pain management. Bupivacaine with epinephrine in TAP blocks provided pain relief comparable to high-volume local port-site infiltration, with a significant benefit in the US-guided TAP block group at 2 h [40]. Thoracic PCEA morphine with bupivacaine was superior to parenteral morphine, significantly reducing pain scores both at rest and during coughing, with PCEA patients reporting less pain overall [41]. Three studies found no significant differences between neuraxial, parenteral, or oral morphine administration methods [43,44,48]. Sugihara et al. observed no overall significant difference in pain scores with the addition of levobupivacaine infiltration, though significant differences were noted at 2 h postoperatively in patients undergoing laparoscopic-assisted vaginal hysterectomy (p = 0.047) and laparoscopic hysterectomy (p = 0.007) [50]. Güngördük et al. found no significant difference in pain scores between local anesthetic (Lidocaine spray on the ectocervix followed by Bupivacaine submucosal injection) and general anesthesia for loop electrosurgical excision procedures [53].

3.10. Holistic and Complementary

Seven studies assessed holistic and complementary medicine. Hou et al. compared Chinese herbal treatment alone versus combined with psychological care in cervical cancer patients, finding no significant difference in acute postoperative pain on days 1 and 7 [11]. Ariyasriwatana et al. observed a significant reduction in pain with Curcumin capsules added to standard analgesia [37]. Similarly, low to medium-intensity walking exercises (at least 150 min per week before surgery) combined with routine nursing care resulted in lower pain scores beyond 24 h [35].
Utilization of an abdominal binder significantly reduced pain on days 1 and 2, but this effect was not sustained on day 3, with no overall change in pain scores from baseline to days 1 to 3 [26]. Postoperative massage or physiotone vibrational medicine, as well as acupuncture administered pre- and postoperatively (daily for up to five days), did not improve pain outcomes [32,45]. Palaia et al. also reported no significant difference between a low-residue and free diet starting three days before surgery [48].

3.11. Quality of Studies

Table 4 summarizes the primary and secondary outcomes assessed in each included trial. Table 5 summarizes our assessment of the quality of the included trials. Overall, the median Jadad score for methodological quality of the included trials was 4 (interquartile range (IQR) 2, minimum 1, maximum 5). The median impact score of the included journals was 2.741 (IQR 2.280, minimum 0.196, maximum 9.872).
Table 4. Summary of outcomes reviewed in the studies. They were categorized according to pain, analgesia consumption, quality of life, physical function, psychological function, satisfaction, physiologic response, adverse events, long term, and procedural or operative outcomes.
Table 5. Summary of journal impact, study funding, Jadad score and study size.
Risk of bias was assessed using the Cochrane Collaboration’s Risk of Bias tool, and results are presented in a risk of bias graph (Supplementary Materials S2). In tumor-specific cancer studies (n = 16), most were judged as low risk for random sequence generation (13), allocation concealment (10), blinding (10), and incomplete outcome data (16), while all had some concerns for selective reporting and other bias. In studies of generic cancers (malignant only, n = 13), high risk of bias was frequently observed for blinding (7), selective reporting (13), and other bias (13), whereas most were low risk for randomization (10) and incomplete outcome data (12). For studies of generic cancers including both benign and malignant cases (n = 17), most were low risk across domains except for selective reporting, where all were rated as high risk.

4. Discussion

Opioids remain the cornerstone of postoperative pain management, as reflected in most RCTs, which typically include an opioid-based study arm. However, balancing the analgesic benefits of opioids with their adverse side effects presents ongoing challenges, such as nausea, constipation, dependence, and tolerance. Moreover, opioids necessitate intensive perioperative monitoring by a vigilant multidisciplinary team to prevent potential toxicity and respiratory depression. Additionally, concerns over opioid over-prescription, a major but often under-recognized risk factor for future misuse and addiction, have prompted increased scrutiny. Evidence suggests that escalating opioid doses may also contribute to chronic postoperative pain development [56,57]. The variability in analgesic outcomes across RCTs investigating opioid use could be attributed to differences in administration routes and opioid types.
To address the opioid-related side effects, non-opioid alternatives such as NSAIDs have gained prominence in postoperative pain management due to their effectiveness in reducing inflammation and alleviating pain. By inhibiting cyclooxygenase enzymes, NSAIDs decrease prostaglandin production, enhancing pain relief while minimizing opioid use. Studies have shown that NSAIDs can reduce postoperative pain compared to controls, with some demonstrating significant benefits such as Parecoxib [8,9,12,13,47]. However, results can vary, as other studies found no significant differences between certain NSAIDs, such as celecoxib and intravenous ketorolac [28,33,52]. Despite their benefits, NSAIDs can pose risks. These include gastrointestinal, renal, and cardiovascular adverse effects, particularly in patients with pre-existing conditions. Additionally, NSAIDs have been associated with increased anastomotic-related complications, such as fistulas and leaks, particularly in extensive cytoreductive procedures involving bowel resections and anastomoses [58]. A meta-analysis revealed that postoperative NSAID use increased the overall risk of anastomotic leakage, with non-selective NSAIDs (e.g., diclofenac) showing a higher risk. Conversely, selective NSAIDs and ketorolac were not significantly associated with this complication [59]. Therefore, careful selection of patients, medication, and monitoring are essential. When used appropriately, NSAIDs can significantly enhance multimodal analgesia strategies for patients undergoing gynecological cancer surgeries.
Other non-opioid options like paracetamol also play a crucial role in multimodal analgesia. Its analgesic effects are primarily due to the central inhibition of prostaglandin synthesis, making it an effective adjunct to opioid and NSAID therapies. One study found that metamizole (without ketoprofen) was inferior to paracetamol when combined with morphine on postoperative day 0. However, a multimodal approach incorporating morphine with either paracetamol and ketoprofen, or metamizole and ketoprofen provided equivalent analgesia, underscoring the effectiveness of paracetamol in postoperative pain management strategies [31].
As opioid-sparing strategies gain importance, agents like dexmedetomidine, an alpha-2 adrenergic agonist, have been increasingly utilized due to their sedative and analgesic properties. By inhibiting norepinephrine release, it induces sedation, reduced anxiety, and enhances pain relief. Studies have shown that dexmedetomidine infusion significantly reduces postoperative pain during activity at one h post-surgery but has no effect at rest or at other time points compared to control [27]. When compared to opioids, conflicting analgesic effects was observed with no significant difference between IV PCA dexmedetomidine and fentanyl [34]. Whereas combining dexmedetomidine and lidocaine significantly lowered pain levels and reduced opioid consumption, thereby minimizing the associated side effects compared to opioid alone [27,34,46]. Potential dexmedetomidine adverse effects include hypotension, bradycardia, and sedation-related complications, necessitating careful patient assessment and monitoring. When used judiciously, it can be a valuable adjunct in multimodal analgesia strategies.
Drug repurposing for postoperative pain management, leveraging the existing safety profiles of medications developed for other conditions, is an emerging strategy to accelerate the identification of effective, opioid-sparing analgesics. Sattari et al. investigated the use of duloxetine, a serotonin-noradrenaline reuptake inhibitor traditionally used for depression, anxiety, and chronic pain. Administering duloxetine two h prior to inducing analgesia significantly reduced pain scores in recovery and on the ward following abdominal hysterectomy for various gynecological indications compared to the control group [50]. This infers a possible alternative pathway in the management of postoperative pain. Anxiety and depression are well established factors influencing the severity of pain and vice versa. Duloxetine increases serotonin and norepinephrine levels which is associated with improved mental well-being whilst effectively managing neuropathic pain. Its dual action emphasizes the importance of integrating psychological well-being and neuropathic pain control for a comprehensive pain management, which is pertinent in major gynae-oncological surgery [60,61,62].
Furthermore, magnesium sulfate ought to be considered as an adjunct in pain management due to its antinociceptive effect. This occurs via the antagonization of NMDA receptors, preventing central sensitization and attenuates pre-existing hyperalgesia. Magnesium sulphate can be administered through various modalities (oral or parenteral) to alleviate pain and has been shown to be effective in cancer-related neurologic symptoms and chemotherapy-induced peripheral neuropathy [24]. While magnesium sulphate is increasingly recognized for its role in pain management, further research is required to elucidate its role as an adjuvant analgesic.
Regional anesthesia offers potential benefits as part of a multimodal approach to postoperative pain management, enhancing analgesic effectiveness and optimizing patient outcomes. Peripheral nerve blocks and fascial plane blocks, including ilioinguinal, iliohypogastric, and ESPB, have demonstrated effective pain relief [11,18], with ESPB outperforming TAPB by reducing tramadol use [20]. Magnesium-enhanced TAP blocks further improved analgesia [24], while intraperitoneal local anesthetics demonstrated limited benefits [22].
Central neuraxial approaches, including epidurals and spinal blocks, have shown effectiveness in certain studies, particularly for pain relief during ambulation and coughing [30,36]. However, overall efficacy is inconsistent when compared to peripheral nerve blockade, parenteral and oral options [25,29,43,44,49]. Complications such as hypotension, impaired mobilization and catheter-related complications may arise, necessitating intensive monitoring [30,36]. Variability in outcomes may be influenced by differences in the analgesics used. A tailored integration of anesthetic modalities could enhance pain management, facilitate earlier mobilization, and support recovery.
Postoperative cancer care involves pain management and addressing the psychological morbidity associated with cancer, which impacts both short- and long-term quality of life. Shi et al. demonstrated improved pain scores through standardized nursing care for cervical cancer patients, involving a dedicated quality control team trained in pain assessment, cancer pain psychology, and analgesic interventions, emphasizing medication compliance and the efficacy of pain medications [14,63]. Similarly, Zhu et al. showed that a standardized empathetic care model, incorporating training in empathetic care, communication, psychological support, interdisciplinary collaboration, enhanced postoperative recovery, improving pain, sleep, and psychological well-being, as reflected in a shorter hospital stay [18]. Future studies should explore integrating empathetic care into routine oncology nursing practice.
In addition to pharmacological approaches, complementary medicine has been considered for their potential to enhance pain relief. It remains a contentious area due to inconsistent standards in preparation and regulation leading to differing pharmacokinetics that ultimately impacts on patient’s response. Hou et al. examined the effects of Chinese herbal treatments combined with psychological care in patients with advanced cervical cancer, finding no significant difference in acute pain relief at day 1 and 7. However, combination therapy was more effective at minimizing pain on day 30 and 60 than Chinese herbal treatments alone [11].
Similarly, curcumin derived from turmeric has anti-inflammatory and antioxidant properties [64]. Ariyasriwatana et al. showed that the addition of curcumin significantly reduced the pain scores at 72 h, but not at 24 h following laparoscopic hysterectomy for multiple gynecology pathology including cancer. This may be attributed to its low bioavailability, with optimum dosage and method of administration yet to be established [37,65].
Acupuncture and massage therapy are alternative modalities that have been explored in pain management, though evidence for their efficacy post-gynecological surgery is limited. Lam et al. found no significant benefit of acupuncture on postoperative pain following laparotomy [45]. Taylor et al. compared Swedish massage with physiotone vibrational therapy on day 1 and 2 postoperatively. There was a non-significant trend towards improved pain scores following Swedish massage in comparison to usual care and physiotone vibrational therapy [32]. This is in keeping with a meta-analysis showing the benefits of massage therapy for surgery-related pain, with foot reflexology being more effective than body or aroma massage [66].
Abdominal binders may be considered in postoperative pain management to aid with mobilization, breathing, and coughing. Ossola et al. systemically reviewed the use of postoperative abdominal binding after midline laparotomy. They identified that abdominal binding significantly reduced postoperative pain on the first and third day and improved physical activity on the third day without impairment of respiratory function [67]. In keeping with this, Chantawong et al. also concluded that abdominal binders were effective at lowering pain scores on days 1 and 2, with no difference identified on day 3. In this trial, patients were not blinded to the intervention and this may have led to reporting bias [26].
Incorporating lifestyle measures such as exercise and diet further enhances the multimodal pain management approach. Early mobilization and structured exercise programs reduce pain, opioid use, and complications such as deep vein thrombosis [35]. It also promotes endorphin release, offering natural pain relief and enhancing functional recovery [68]. Additionally, diet plays a pivotal role in managing pain and recovery. Anti-inflammatory diet rich in fruits, vegetables, omega-3 fatty acids, and antioxidants helps reduce inflammation and pain. Adequate protein supports tissue healing, while stable blood glucose levels prevent delayed recovery. Hydration and electrolyte balance, particularly with magnesium, are also key in minimizing pain and enhancing healing. Incorporating exercise and a nutrient-rich diet into postoperative care can improve pain management and recovery, complementing traditional analgesic approaches [48,69].
Numerous studies have identified risk factors which may lead to suboptimal postoperative pain relief including: (1) age (increasing age may be associated with altered pain perception and metabolism of analgesics); (2) comorbidities (e.g., chronic pain conditions, previous surgery, psychological factors, high BMI); (3) medications (opioid tolerance, drug interactions); (4) lifestyle factors (substance misuse, smoking); (5) type and extent of surgery; (6) postoperative factors (inadequate or poor compliance pain management, complications); and (7) psychosocial factors (mental well-being, social support) [70,71]. These factors emphasize the complex interplay influencing pain, underscoring the requirements of a multidisciplinary approach and continuous assessment to optimize postoperative pain management.
Inadequate postoperative pain control can lead to prolonged bed rest and immobility, which increase the risk of complications such as venous thromboembolism, hospital-acquired infections, and functional decline. This issue is particularly pertinent in gynecologic oncology surgery, where extended hospitalization is common, especially among patients with vulvar cancer. The lack of specific studies addressing postoperative pain management in this subgroup highlights a significant gap in the literature. Effective pain control is imperative to mitigate immobility-related morbidity, reduce health economic burden, and improve overall outcomes [5,72].
Procedure-specific pain management is essential to optimize recovery and prevent chronic pelvic pain. While MIS patients are often presumed to exhibit less postoperative pain, this assumption may be influenced by variation in perioperative management standards. Patients undergoing radical open surgeries typically receive regional anesthesia and oversight from acute pain services, whereas MIS patients often do not [62,73]. Only 3 RCTs encompassed both MIS and open surgery, but neither compared postoperative pain outcomes amongst surgical approach.
The inclusion of both benign and malignant gynecologic surgeries introduces clinical variability that limits direct comparability. Furthermore, the aggregation of distinct gynecologic cancer subtypes presents additional complexity due to their differing biological behaviors and treatment paradigms. Future RCTs should implement stratification by surgical indication and cancer subtype to enhance the validity and applicability of findings.

5. Limitations

This review has several limitations that may affect the validity and generalizability of its findings. The included studies showed significant heterogeneity in design, sample size, and methodologies, complicating comparisons and precluded a quantitative meta-analysis. Variability in pain assessment tools and outcome measures hindered consistent data reporting. Most studies had short follow-up periods, limiting long-term evaluation of pain management and recovery. The lack of standardized pain management protocols and insufficient focus on multimodal approaches restricted insights into effective strategies. Many studies did not assess patient-reported outcomes or control for confounding variables, such as comorbidities and psychological factors, which are essential for understanding pain and recovery. Furthermore, the absence of subgroup or sensitivity analyses limits the interpretability of the review’s findings. Importantly, studies categorized as generic cancers and generic (benign and malignant) groups were at a higher risk of bias, largely due to selective reporting bias stemming from the absence of tumor-specific data breakdowns. This limitation may reduce confidence in the findings from these subsets and restrict the generalizability of the conclusions.

6. Conclusions

The limited cancer- and procedure-specific trials, combined with the diverse analgesic modalities employed, underscore the complexity of pain management, emphasizing the importance of a multimodal approach. Notably, no studies specifically addressed postoperative pain in vulval cancer, highlighting a significant gap in existing literature and underscoring the need for targeted research in this underrepresented patient group.
The studies revealed significant heterogeneity and a lack of standardized pain assessment methods. A consensus on quantifiable tools is essential for evaluating pain management efficacy. While no single analgesic modality proved superior, trends suggest multimodal approaches may offer better pain control. Additionally, integrating psychological well-being management is crucial alongside pharmacological relief.
These findings emphasize the urgent need for clear, standardized, and evidence-based guidelines to ensure equitable, effective, and individualized postoperative pain management across all gynecological cancer populations.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/cancers17162718/s1, Table S1: Electronic literature search strategies and Table S2: Risk of bias.

Author Contributions

Conceptualization, S.S. (Sanooj Soni), S.C. and H.S.; methodology, S.C. and H.S.; formal analysis, S.C. and H.S.; data curation, S.C. and H.S.; writing—original draft preparation, S.C. and H.S.; writing—review and editing, X.Z., A.M., F.S., J.R.S., J.Y., S.G.-M., S.S. (Sanooj Soni), C.F., S.S. (Srdjan Saso); visualization, S.C. and H.S.; supervision, S.S. (Srdjan Saso). All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
BMIBody Mass Index
CEAContinuous Epidural Analgesia
CENTRALCochrane Central Register of Controlled Trials
CRBSContinuous Rectus Sheath Block
ESPBErector Spinae Plane Block
HSInitials of Reviewer/Author
IQRInterquartile Range
IVIntravenous
MISMinimally Invasive Surgery
NMDAN-methyl-D-aspartate (as in NMDA receptor)
NRSNumerical Rating Scale
NSAIDsNon-Steroidal Anti-Inflammatory Drugs
PCAPatient-Controlled Analgesia
PCEAPatient-Controlled Epidural Analgesia
PACUPost-Anesthesia Care Unit
PRISMAPreferred Reporting Items for Systematic Reviews and Meta-Analyses
RCT(s)Randomized Controlled Trial(s)
SPSSStatistical Package for the Social Sciences
SSInitials of Reviewer/Author
TAP/TAPBTransversus Abdominis Plane/Transversus Abdominis Plane Block
USAUnited States of America
USUltrasound
VASVisual Analog Scale

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Comprehensive Longitudinal Linear Mixed Modeling of CTCs Illuminates the Role of Trop2, EpCAM, and CD45 in CTC Clustering and Metastasis
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Complete Mesocolic Excision for Colon Cancer: Insight into Potential Mechanisms of Oncologic Benefit
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