Miralpeix et al. World Journal of Surgical Oncology (2022) 20:46 https://doi.org/10.1186/s12957-022-02517-1 RESEARCH Open Access Impact of prehabilitation during neoadjuvant chemotherapy and interval cytoreductive surgery on ovarian cancer patients: a pilot study Ester Miralpeix1,2*, Josep‑Maria Sole‑Sedeno1,2, Cristina Rodriguez‑Cosmen3, Alvaro Taus4,5, Maria‑Dolors Muns6, Berta Fabregó1 and Gemma Mancebo1,2 Abstract Background: Cytoreductive surgery followed by systemic chemotherapy is the standard of treatment in advanced ovarian cancer where feasible. Neoadjuvant chemotherapy (NACT) followed by surgery is applicable where upfront cytoreductive surgery is not feasible because of few certain reasons. Nevertheless, surgical interventions and the chemotherapy itself may be associated with postoperative complications usually entailing slow postoperative recov‑ ery. Prehabilitation programs consist of the patient’s preparation before surgery to improve the patient’s functional capacity. The aim of this study was to evaluate the impact of a prehabilitation program during neoadjuvant treatment and interval cytoreductive surgery for ovarian cancer patients. Methods: A retrospective observational pilot study of patients with advanced ovarian cancer treated with NACT and interval cytoreductive surgery was conducted. The prehabilitation group received a structured intervention based on physical exercise, nutritional counseling, and psychological support. Nutritional parameters were assessed preopera‑ tively and postoperatively, and functional parameters and perioperative and postoperative complications were also recorded. Results: A total of 29 patients were included in the study: 14 in the prehabilitation group and 15 in the control group. The patients in the prehabilitation program showed higher mean total protein levels in both preoperative (7.4 vs. 6.8, p = 0.004) and postoperative (4.9 vs. 4.3, p = 0.005) assessments. Up to 40% of controls showed intraoperative com‑ plications vs. 14.3% of patients in the prehabilitation group, and the requirement of intraoperative blood transfusion was significantly lower in the prehabilitation group (14.3% vs. 53.3%, p = 0.027). The day of the first ambulation, rate of postoperative complications, and length of hospital stay were similar between the groups. Finally, trends towards shorter time between diagnosis and interval cytoreductive surgery (p = 0.097) and earlier postoperative diet restart (p = 0.169) were observed in the prehabilitation group. Conclusion: Prehabilitation during NACT in women with ovarian cancer candidates to interval cytoreductive surgery may improve nutritional parameters and thereby increase postoperative recovery. Nevertheless, the results of this pilot study are preliminary, and further studies are needed to determine the clinical impact of prehabilitation programs. *Correspondence: ester.miralpeix@gmail.com 2 Universitat Pompeu Fabra, Barcelona, Spain Full list of author information is available at the end of the article © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://​creat​iveco​mmons.​org/​licen​ses/​by/4.​0/. The Creative Commons Public Domain Dedication waiver (http://​creat​iveco​ mmons.​org/​publi​cdoma​in/​zero/1.​0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Miralpeix et al. World Journal of Surgical Oncology (2022) 20:46 Page 2 of 10 Keywords: Prehabilitation, Neoadjuvant chemotherapy, Interval cytoreductive surgery, Ovarian cancer Introduction before interval cytoreductive surgery in patients with Advanced ovarian cancer is a complex and challeng- advanced ovarian cancer could enhance patients’ func- ing disease whose treatment requires a multimodal tional capacity. With this purpose, we formed a multi- approach [1]. Primary treatment consists of optimal pri- disciplinary team to implement a pilot prehabilitation mary cytoreductive surgery followed by systemic chemo- program to support gynecologic oncology patients. The therapy. In patients unsuitable for primary cytoreductive aims of this study were to evaluate our initial experience surgery due to advanced age, frailty, poor performance and impact of a multimodal prehabilitation program status, comorbidities, or disease that is unlikely to be in advanced-stage ovarian cancer patients undergoing optimally cytoreduced, neoadjuvant chemotherapy interval cytoreductive surgery. (NACT) followed by interval cytoreductive surgery should be considered [2, 3]. Therefore, cytoreductive sur- Materials and methods gery after NACT is often undertaken in patients who are Design and subjects physically, nutritionally, and/or psychologically affected. A retrospective pilot observational study of patients The aim of NACT is to achieve radiological and clini- undergoing interval cytoreductive surgery for ovarian cal improvement to increase the likelihood of optimal cancer was conducted at the Hospital del Mar Barcelona cytoreduction at interval cytoreductive surgery [4, 5]. between January 2015 and June 2020. Many patients with advanced ovarian cancer present Eligible patients were women diagnosed with advanced with abdominal disease that can lead to malnutrition, and ovarian cancer undergoing interval cytoreductive sur- some patients present physiological effects of peripheral gery after standardized 3 cycles of NACT with carbopl- muscle wasting, decreased exercise tolerance and fatigue, atin and paclitaxel. In previous interval cytoreductive and psychological morbidity for anxiety of a potentially surgery, all patients were evaluated through laparoscopic terminal cancer diagnosis [6]. Surgery is an aggressive approach and computed tomography scan to consider procedure that disrupts the physiologic status and triggers optimally resectable disease by a multidisciplinary team. a general stress response, altering hormonal, metabolic, The exclusion criteria were inability to give informed immunologic, and neurological functions, and NACT consent, having non-resectable disease, inability to treatment may also affect the physiologic status and body perform exercises with locomotor limitations, cogni- function [7]. In particular, cytoreductive surgery usu- tive deterioration impeding adherence to the program, ally requires peritonectomy, lymphadenectomy, visceral patients who declined surgery or NACT, or those who resection, and gastrointestinal anastomoses [8, 9]. There- received non-standard NACT. The prehabilitation pro- fore, it seems appropriate to restore the baseline status of gram was implemented in January 2018, and the first ovarian cancer patients before exposition to another acute patients that followed the prehabilitation program were stressor such as surgery and especially after NACT. The consecutively included in this pilot study. Patients treated period on NACT before interval cytoreductive surgery before this date were used as a control group. offers a window of opportunity to improve the patient’s functional capacity or to restore its capacity to baseline Prehabilitation intervention levels [10, 11]. The prehabilitation program was developed by a mul- Prehabilitation programs consist of the patient’s tidisciplinary team of gynecologists, anesthesiologists, preparation between diagnosis and surgery to improve physiotherapists, dieticians, psychologists, and geri- functional capacity and metabolic reserves before the atricians. The prehabilitation group received a structured intervention, resulting in a reduction of perioperative intervention including physical exercise recommenda- complications. Multimodal prehabilitation may include tions, nutritional counseling, and psychological support. exercise, nutritional counseling, psychological support, This program was extensively described in a previous and optimization of underlying conditions, as well as publication [15]. Briefly, all patients included in the pre- cessation of negative health behaviors such as alcohol habilitation program received recommendations for or tobacco consumption [12]. Emerging evidence sug- daily exercise practice, nutritional counseling based on gests that multimodal prehabilitation programs in major homemade recipes of protein supplementation and psy- cancer surgeries have a positive impact on the patients’ chological support, and a preoperative carbohydrate outcomes [13, 14]. Therefore, it would be expected that loading and an inspiratory threshold-loading device in a multimodal prehabilitation program during NACT our consultation. Patients in the prehabilitation program Miralpeix et al. World Journal of Surgical Oncology (2022) 20:46 Page 3 of 10 received perioperative care, following the guidelines of Statistical methods the Enhanced Recovery After Surgery (ERAS) program, Statistical analysis was performed using SPSS 21.0 (Chi- which has been the standard of surgical approach for our cago, IL, USA) assuming a statistically significant level of patients since 2015 [16, 17]. The control group received 5% (p < 0.05). Participant demographic and clinical char- standard of care, and no specific intervention before sur- acteristics were summarized using descriptive statistics. gery was administered. Continuous variables were reported as mean (range) or The length of the prehabilitation program was not fixed mean ± standard deviation (SD) when indicated, and and depended on the patient’s status, tumor type, and categorical variables were reported as frequency and per- extension. In addition, the duration also depended on centage (%). Pearson’s chi-square test or Fisher exact test the time period before surgery, which was modulated by was used to compare categorical variables, and Student’s NACT tolerance and toxicity, organizational aspects of t-test or non-parametric Mann-Whitney test was used healthcare providers, and by type of surgical intervention. for continuous variables, when appropriate. Variables and outcomes Ethical considerations Demographic and clinical baseline information was col- The study was evaluated and approved by the institu- lected retrospectively from medical registries. Nutritional tional ethics committee (Institutional Review Board Pro- status was evaluated by total serum protein, albumin, ject No. 2017/7770/I). All participants provided a written hemoglobin, and prealbumin levels. Measurements were informed consent. recorded at diagnosis, just before the interval surgery, 48–72 h post-surgery, and 1 month after surgery. The Results main surgical, intraoperative, and postoperative param- A total of 29 patients undergoing interval cytoreduc- eters reported included peri- and postoperative compli- tive surgery for ovarian cancer were included in the cations, postoperative pain, length of hospital stay, days study. Overall, 15 patients were included in the control of intensive care unit (ICU) stay, day of the first ambu- group and 14 in the prehabilitation group. The mean lation, and readmission rates. Complications were clas- age of patients was 64.5 ± 8.8 years (range 51–83). sified according to Clavien-Dindo classification (grades Baseline demographic and clinical characteristics I–V) [18]. The complexity of the surgical procedure was of the study population are shown in Table 1. There classified using Aletti’s surgical complexity score (SCS), were no significant differences in age, clinical disease based on the number and the complexity of the surgical stage, or comorbidities between the groups. It should procedures performed [19]. be mentioned that the mean time between diagnosis Table 1 Baseline demographic and clinical characteristics of the study population Control group (n = 15) Prehabilitation group (n =14) p-value Age (years), mean ± SD 63.8 ± 7.6 65.1 ± 10.2 0.689 BMI (kg/m2), mean ± SD 27.2 ± 5.7 29.3 ± 6.1 0.360 Disease stage, n (%) III 8 (53.3) 7 (50.0) 0.858 IV 7 (46.7) 7 (50.0) Medical history, n (%) Heart disease 2 (13.3) 1 (7.1) 0.584 Diabetes 2 (13.3) 3 (21.4) 0.564 Anticoagulation 2 (13.3) 0 (0) 0.157 Smoking 6 (40.0) 3 (21.4) 0.270 Alcohol 2 (13.3) 0 (0) 0.157 ASA class, n (%) II 6 (40.0) 9 (64.3) 0.323 III 8 (53.3) 5 (35.7) IV 1 (6.7) 0 (0) Time between diagnosis and interval surgery 15.3 ± 3.2 [11.3–24.3] 13.5 ± 2.0 [11.4–18.0] 0.097 (weeks), mean ± SD [range] ASA American Society of Anesthesiologists, BMI body mass index, COPD chronic obstructive pulmonary disease, SD standard deviation Miralpeix et al. World Journal of Surgical Oncology (2022) 20:46 Page 4 of 10 and interval cytoreductive surgery was shorter in the Figure 1 shows the total serum protein value evolution prehabilitation group than in controls (13.5 vs. 15.3 in the control and prehabilitation groups. weeks, p = 0.097). During this time period, patients Regarding the impact of the prehabilitation program were on NACT treatment, and the intervention group on surgical and intraoperative parameters, no significant followed the prehabilitation recommendations. Thus, differences in length of surgery or surgical procedure control patients required more time on NACT before complexity between the groups were observed (Table 3). the surgery was performed, although it was not statis- However, although preoperative hemoglobin levels were tically significant. similar between the groups, the prehabilitation group The results comparing the impact of the prehabili- showed a significantly lower intraoperative blood trans- tation program on nutritional parameters are shown fusion rate (14.3%) compared with the control group in Table 2. Prehabilitation group patients received a (53.3%) (p = 0.027), as well as a trend towards lower preoperative carbohydrate loading; however, this was intraoperative vasoactive drug requirement (7.1% vs. not associated with an increased intraoperative risk of 20.0%). The incidence of intraoperative complications hyperglycemia (p = 0.668), nor postoperative insulin showed a trend towards fewer complications in the pre- requirement (p = 0.782). In addition, the mean value habilitation group (40% of patients in the control group of preoperative Hb1Ac was not different between the vs. 14.3% in the prehabilitation group). groups (p = 0.382), and no significant differences in When considering the postoperative outcomes, no serum total proteins, albumin, prealbumin, and hemo- significant differences regarding the length of stay, time globin levels were noted at diagnosis. to start adjuvant chemotherapy, and postoperative pain In contrast, the prehabilitation group showed higher control between the groups were observed. Additionally, preoperatively protein levels compared to the con- prehabilitation was not associated with increased risk of trol group (7.4 vs. 6.8, p = 0.004). In addition, postop- postoperative complications, reintervention, readmission erative serum total proteins and albumin values were rate, or mortality, although one patient in the control higher in the prehabilitation group (p = 0.005 and p = group died due to severe postoperative complications and 0.021, respectively). Although not significant, a trend to none in the prehabilitation group. To note, the incidence higher postoperative levels of prealbumin and hemo- of postoperative complications was similar between the globin was also detected in the prehabilitation group. groups, according to the Clavien-Dindo classification. Table 2 Impact of the prehabilitation program on nutritional parameters Control group (n = 15) Prehabilitation group p-value (n = 14) Preoperative HbA1c (%) 5.6 ± 0.6 5.8 ± 0.6 0.382 Intraoperative glucose (BMTest) (mg/dl) 162.7 ± 38.0 154.7 ± 53.5 0.668 Postoperative insulin requirement, n (%) 5 (33.3%) 4 (28.6%) 0.782 Diagnosis Total protein (g/dl) 6.7 ± 0.7 6.8 ± 0.4 0.510 Albumin (g/dl) 3.9 ± 0.5 3.9 ± 0.4 0.959 Prealbumin (mg/dl) 15.6 ± 6.2 14.2 ± 6.6 0.683 Hemoglobin (g/dl) 12.0 ± 1.8 12.2 ± 1.6 0.843 Preoperative Total protein (g/dl) 6.8 ± 0.5 7.4 ± 0.3 0.004 Albumin (g/dl) 4.1 ± 0.5 4.4 ± 0.3 0.209 Prealbumin (mg/dl) 20.2 ± 4.9 22.4 ± 4.3 0.428 Hemoglobin (g/dl) 10.8 ± 1.0 10.8 ± 0.9 0.915 Postoperative Total protein (g/dl) 4.3 ± 0.7 4.9 ± 0.6 0.005 Albumin (g/dl) 2.4 ± 0.6 2.8 ± 0.4 0.021 Prealbumin (mg/dl) 9.5 ± 3.3 12.5 ± 4.3 0.124 Hemoglobin (g/dl) 9.5 ± 1.0 8.9 ± 1.3 0.164 One month postoperative Total protein (g/dl) 7.0 ± 0.7 7.2 ± 0.5 0.693 Albumin (g/dl) 4.2 ± 0.5 4.2 ± 0.4 0.985 Prealbumin (mg/dl) 20.7 ± 8.2 22.2 ± 5.3 0.465 Hemoglobin (g/dl) 11.2 ± 1.0 11.2 ± 1.4 0.683 Data are presented as mean ± SD, unless otherwise specified Miralpeix et al. World Journal of Surgical Oncology (2022) 20:46 Page 5 of 10 Fig. 1 Serum total protein value evolution Table 3 Intraoperative and surgical outcomes Control group (n = 15) Prehabilitation group (n = 14) p-value Surgical approach Laparoscopic 2 (13.3) 0 (0) 0.157 Laparotomic 13 (86.7) 14 (100) Intestinal resection 1 (6.7) 2 (14.3) 0.501 Epidural anesthesia 11 (73.3) 11 (78.6) 0.742 Surgical time (min) mean ± SD 309.0 ± 76.7 300.0 ± 87.7 0.770 Aletti’s SCS, mean ± SD 5.0 ± 1.2 5.1 ± 2.6 0.927 Intraoperative blood transfusion 8 (53.3) 2 (14.3) 0.027 Intraoperative vasoactive drugs 3 (20.0) 1 (7.1) 0.316 Intraoperative complications 6 (40.0) 2 (14.3) 0.122 Vascular 3 (20.0) 1 (7.1) 0.316 Intestinal 2 (13.3) 1 (7.1) 0.584 Urological 1 (6.7) 1 (7.1) 0.960 Cardiovascular 0 (0) 0 (0) - Data are presented as n (%), unless otherwise specified SCS surgical complexity score, SD standard deviation Furthermore, the prehabilitation group showed a trend prehabilitation group that may contribute to reduce peri- towards earlier postoperative diet restart compared with operative complications and also to improve postopera- the control group (1.3 days vs. 1.7 days). All postoperative tive recovery. and functional results are shown in Table 4. Prehabilitation programs consist of the patient’s preparation between diagnosis and surgery to improve Discussion functional capacity and metabolic reserves before inter- This pilot study reported our initial experience in imple- vention. Previous studies have shown that multimodal menting a prehabilitation program for ovarian cancer prehabilitation programs in major cancer surgeries have a patients undergoing NACT and interval cytoreductive positive impact on the patients’ outcomes [13, 14]. surgery, being the first study assessing the impact of a Patients in the prehabilitation group showed higher prehabilitation intervention. The main results showed a pre- and postoperative serum total protein and postop- nutritional improvement among patients included in the erative albumin levels. Given that baseline nutritional Miralpeix et al. World Journal of Surgical Oncology (2022) 20:46 Page 6 of 10 Table 4 Postoperative outcomes Control group, mean ± SD (n Prehabilitation group, mean ± SD p-value = 15) (n = 14) Hospital stay (days) 7.8 ± 6.8 7.4 ± 5.0 0.700 ICU stay (days) 1.2 ± 0.6 1.2 ± 0.9 0.959 Time to start CT of surgery day (days) 39.9 ± 14.3 37.4 ± 9.2 0.602 Pain VAS day 1 1.6 ± 1.7 1.7 ± 1.7 0.856 Pain VAS day 2 1.2 ± 1.0 1.4 ± 1.4 0.736 Diet restart (days) 1.7 ± 0.8 1.3 ± 0.6 0.169 Deambulation restart (days) 3.1 ± 1.2 2.9 ± 1.4 0.678 Postoperative complications, n (%) Non reported 6 (40.0) 4 (28.6) 0.518 Reported 9 (60.0) 10 (71.4) Postoperative complications Paralytic ileus 2 (13.3) 1 (7.1) 0.584 Surgical site infection (superficial and deep) 6 (40.0) 5 (35.7) 0.812 Surgical site infection (organ and space) 2 (13.3) 0 (0) 0.157 Anastomosis breakdown 2 (13.3) 0 (0) 0.157 Cardiovascular 1 (6.7) 0 (0) 0.326 Respiratory 3 (20.0) 1 (7.1) 0.316 Neurological 0 (0) 2 (14.3) 0.129 Urinary tract infection 4 (26.7) 1 (7.1) 0.164 Multiorgan failure 1 (6.7) 0 (0) 0.326 Surgical reintervention 1 (6.7) 1 (7.1) 0.960 Clavien-Dindo complications I 4 (26.7) 4 (28.6) 0.486 II 10 (66.7) 8 (57.1) III 0 (0) 1 (7.1) IV 0 (0) 1 (7.1) V 1 (6.7) 0 (0) Readmissions 2 (13.3) 3 (21.4) 0.564 CT chemotherapy, ICU intensive care unit, SD standard deviation, VAS visual analog scale parameters at diagnosis were similar between the groups, be taken into account that complications after surgery the combination of both physical exercise and pro- are related to surgical parameters but also depend on tein supplements 30 min after exercise training could patient factors [21]. A study of patients with colorectal have enhanced muscle hypertrophy and impacted body cancer resection showed no significant beneficial reduc- mass composition and nutritional status. In this line, in tion in postoperative complications following nutritional patients with rectal cancer having neoadjuvant chemo- supplementation, although patients who received whey radiotherapy, prehabilitation was linked to an increase in protein supplementation 4 weeks before surgery had patients’ muscle mass [20]. a mean improvement in functional walking capacity Overall, up to 40% of controls showed intraoperative [22]. Similarly, a prospective randomized study in non- complications vs. 14.3% of patients in the prehabilita- malnourished patients undergoing abdominal cancer tion group; however, the potential role of nutritional surgery showed that patients who received nutritional status on reducing perioperative and postoperative supplementation for 14 days before surgery significantly complications is still under investigation. Interestingly, reduced postoperative complications. The laboratory 2 (13.3%) patients in the control group presented anas- parameters decreased in the control group, and in the tomosis breakdown, while no patients in the interven- nutritional supplementation group, they were stable tion group suffered this postoperative complication. (albumin and total protein) or raised (transferrin and Whether anastomosis breakdown and other postop- total lymphocyte count) after surgery [23]. Besides, pro- erative complications could be related to poor nutrition tein supplementation alone has been shown to improve status is a hypothesis that cannot be ruled out. It should nutritional parameters. Yi et al. randomized 118 patients Miralpeix et al. World Journal of Surgical Oncology (2022) 20:46 Page 7 of 10 undergoing elective surgery for gynecological cancer to programs are feasible and safe with a protective factor for preoperative carbohydrate-only loading versus whey postoperative complications [33–36]. protein-infused carbohydrate loading. The whey protein- Interestingly, our results showed that the prehabilita- infused carbohydrate loading group had shorter hospi- tion group reported significantly lower requirements of tal stay, lower readmission rate within 1 month, lower intraoperative blood transfusion rate and a trend towards weight loss, lower C-reactive protein/albumin ratio, pre- lower intraoperative vasoactive drug requirement. In this served muscle mass, and better handgrip strength when line, a randomized control trial of patients submitted to compared to the preoperative carbohydrate-only loading elective major abdominal surgery also showed a trend group [24]. toward lower requirements of vasoactive drugs during In our study, an improvement in preoperative nutri- surgery in the prehabilitation group (p = 0.053) [13]. This tional status was observed. In this way, several studies fact could suggest that prehabilitation would improve tol- in advanced ovarian cancer patients correlated a low erability during surgery avoiding hypotension and hypo- serum preoperative albumin and prognostic nutri- volemic shock. tional index with a worse overall survival [25, 26]. In Although the recommended length for a prehabilita- addition, two prospective studies about major abdomi- tion period is 2–4 weeks before surgery [15], in the pre- nal surgery correlated an early postoperative serum sent study, the length of the prehabilitation program was albumin and total protein drop with postoperative larger, since depended on patients’ disease and individ- complications [27, 28]. Overall, poor preoperative ual response to NACT. The period on NACT treatment nutritional status reflects poor postoperative nutri- is a great opportunity to improve functional capacity tional status, which is associated with higher postoper- through a prehabilitation program. Given that type of ative morbidity. Moreover, a review of Obermair et al. surgical intervention, surgical complexity, and clinical suggests that receiving perioperative nutritional inter- characteristics were well-balanced between the groups, ventions 1–2 weeks prior to surgery and nutritional the duration of the prehabilitation mainly depended on interventions of early postoperative feeding can reduce NACT tolerance and toxicity. Interestingly, a shorter the length of hospital stay and postoperative compli- time between diagnosis and interval cytoreductive sur- cations in gynecological cancer patients undergoing gery in the prehabilitation group was observed suggest- major surgery [29]. ing a better tolerability to chemotherapy in prehabilitated Overall, preoperative carbohydrate loading has been patients. Other studies also demonstrated that prehabili- shown to be an effective method to control postopera- tation program during neoadjuvant treatment is feasible, tive insulin resistance [30, 31]. However, data are lim- safe, and well-tolerated in patients with esophagogastric ited concerning the effects of carbohydrate loading on cancer and it has positive effects in increasing exercise preoperative hyperglycemia and insulin management in capacity before surgery and lower risks of postoperative patients with ovarian cancer patients previous to inter- pneumonia [10, 11, 32, 37]. val cytoreductive surgery. This study adds evidence for recommending routine preoperative carbohydrate load- Strengths and weaknesses ing. Preoperative carbohydrate loading in our preha- This study has several strengths that deserve to be com- bilitation group was not associated with intraoperative mented on. To our knowledge, this is the first study increased risk of hyperglycemia, postoperative insulin assessing the impact of prehabilitation programs in requirement neither intraoperative nor postoperative patients with ovarian cancer undergoing interval cytore- complications. Similarly, Alimena et al. reported that ductive surgery after NACT. Moreover, in our center, carbohydrate loading was associated with an increase in prehabilitation program is a routine preoperative assess- preoperative glucose values without impacting the com- ment of gynecologic oncologic patients before surgery. plication rates [31]. Additional strengths include an homogeneous study pop- Our results also showed that the prehabilitation pro- ulation both at demographics and clinical characteristics gram was safe with no adverse events or increase of peri- with advanced-stage ovarian cancer patients undergoing operative complications. Although there are few studies interval cytoreductive surgery after 3 cycles of NACT. available about prehabilitation and postoperative compli- On the other hand, potential weaknesses of our study cations, published data suggest a potential benefit of the include the non-randomized control trial design and prehabilitation program in terms of postsurgical read- the inherent limitations associated with a retrospec- missions rates and postoperative complications [13, 32]. tive study, where some data or complications may have Systematic reviews and meta-analysis of prehabilitation been missed. However, the enrollment of all consecutive programs for patients undergoing major abdominal sur- patients reduced the chance of selection bias, and clinical gery and oncologic surgery reported that prehabilitation stage and comorbidities were well matched between the Miralpeix et al. World Journal of Surgical Oncology (2022) 20:46 Page 8 of 10 groups. In addition, it was a pilot study with small sample patients with advanced-stage ovarian cancer before size and, therefore, limited statistical power. As this was a interval cytoreductive surgery. The period during neoad- preliminary study, the sample size was decided arbitrar- juvant treatment is a great opportunity to improve the ily, and the results may not be able to properly detect the patient’s functional capacity through a prehabilitation precise differences. Besides, the single-center design may program. have limited the generalizability of the results. However, a qualitative data collection method was used before sur- Abbreviations gery to ensure that patients included in the final analysis SPSS: Statistical Package for Social Sciences; NACT​: Neoadjuvant chemo‑ followed prehabilitation recommendations. Although no therapy; ERAS: Enhanced Recovery After Surgery; ICU: Intensive care unit; SGS: formal data analysis of adherence and acceptability was Surgical complexity score; SD: Standard deviation. performed due to the clinical setting of the study, the Acknowledgements study results may be feasibly imputed to the prehabilita- The authors would like to acknowledge the multidisciplinary team that col‑ tion program. laborates with the prehabilitation program. Finally, it has to be noted that the COVID-19 outbreak Authors’ contributions may have had an impact on the results, given that organi- Study concepts: EM, GM, CRC, and MDM. Study design: EM, JMSS, AT, GM, zational aspects of healthcare providers were truncated and CRC. Data acquisition: BF, EM, and JMSS. Quality control of data and algo‑ rithms: BF and MDM. Data analysis and interpretation: EM, GM, JSS, and CRC. by this pandemic and the study was carried out in two Statistical analysis: EM. Manuscript preparation: EM, BF, and GM. Manuscript different scenarios. Besides, the physical and psychologi- editing: CRC, AT, and MDM. Manuscript review: EM, JMSS, CRC, AT, MDM, BF, cal impacts of lockdown on patients included cannot be and GM. The authors read and approved the final manuscript. ruled out. Authors’ information Twitter handle: @ester_miralpeix (Ester Miralpeix). Implications for practice and future research Funding Our findings seem to suggest preoperative and post- There was no funding for this study. operative nutritional improvements in prehabilitated Availability of data and materials patients, but given the preliminary nature of the design, The datasets generated and/or analyzed during the current study are not this study is mainly intended to stimulate further inves- publicly available but are available from the corresponding author (Miralpeix, tigations to assess the efficacy of surgical prehabilitation Ester) on reasonable request. in gynecologic oncology patients, specifically in patients with ovarian cancer. Our findings warrant future pro- Declarations spective evaluation and support the investigation of Ethics approval and consent to participate prehabilitation programs. Moreover, the study provides The study was evaluated and approved by the institutional Ethics Committee data contributing to the larger body of evidence and of the Hospital del Mar (Institutional Review Board Project No. 2017/7770/I). All participants provided a written informed consent. also for eventual reviews or meta-analysis to help clarify the value of prehabilitation programs in ovarian cancer Consent for publication patients. Not applicable Future larger and adequately powered studies will Competing interests help to evaluate the effect of prehabilitation on post- The authors declare that they have no competing interests. operative surgical, physical, and metabolic outcomes, Author details while investigating tolerance to NACT and onco- 1 Department of Obstetrics and Gynecology, Hospital del Mar, Universitat logic outcomes and periodically evaluate success with Autònoma de Barcelona, Passeig Marítim 25‑29, E‑08003 Barcelona, Spain. 2 quality improvement initiatives. Finally, although Universitat Pompeu Fabra, Barcelona, Spain. 3 Department of Anesthesia, Hospital del Mar, Barcelona, Spain. 4 Department of Medical Oncology, Hospital standardized prehabilitation guidelines for ovarian del Mar, Barcelona, Spain. 5 Cancer Research Program, IMIM (Hospital del Mar cancer patients need to be established, we encour- Institute of Medical Research), Barcelona, Spain. 6 Department of Endocrinol‑ age all groups to prehabilitate ovarian cancer patients ogy, Hospital del Mar, Barcelona, Spain. undergoing interval cytoreductive surgery, based on Received: 29 October 2021 Accepted: 10 February 2022 the ERAS guidelines. Conclusions In conclusion, a trimodal prehabilitation program com- References prising exercise, nutritional supplementation, and psy- 1. Holschneider CH, Berek JS. Ovarian cancer: epidemiology, biology, and prognostic factors. 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