Search

Simple Summary: Percutaneous cryoablation (PCA) is a minimally invasive procedure that should be considered in comorbid patients with stage T1 renal tumours who are suboptimal candidates for partial nephrectomy (PN). However, there is a scarcity of scientific data regarding the efficacy of PCA. The aim of this meta-analysis was to compare PCA and PN in terms of complications, renal function and survival outcomes. According to this analysis, PCA is associated with fewer complications than PN. Moreover, in tumours up to 4 cm, it provides the same time without local recurrence. Therefore, PCA should be proposed to patients with cT1 renal tumours who are not fit for PN but want to undergo a radical treatment. Percutaneous cryoablation (PCA) can be an alternative to partial nephrectomy (PN) in selected patients with stage T1 renal tumours. Existing meta-analyses regarding ablative techniques compared both laparoscopic and PCA with PN. That is why we decided to perform a meta-analysis that focused solely on PCA. The aim of this study was to compare the complications and functional and oncological outcomes between PCA and PN. A systematic literature search was performed in January 2024. Data for dichotomous and continuous variables were expressed as pooled odds ratios (ORs) and mean differences (MDs), both with 95% confidence intervals (CIs). Effect measures for the local recurrence-free survival (LRFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) were expressed as pooled hazard ratios with 95% CIs. Among 6487 patients included in the 14 selected papers, 1554 (23.9%) and 4924 (76.1%) underwent PCA and PN, respectively. Compared with the PN group, patients undergoing PCA had significantly lower overall and major postoperative complication rates. There was no difference in renal function between PCA and PN groups. When analysing collective data for cT1 renal carcinoma, PCA was associated with worse LRFS compared with PN. However, subgroup analysis revealed that in the case of PCA, LRFS was not decreased in patients with cT1a tumours. Moreover, patients undergoing robotic-assisted PN had improved LRFS compared with those undergoing PCA. No significant differences were observed between PCA and PN in terms of MFS and CSS. Finally, PCA was associated with worse OS than PN in both collective and subgroup analyses. In conclusion, PCA is associated with favourable postoperative complication rates relative to PN. Regarding LRFS, PCA is not worse than PN in cT1a tumours but has a substantially relevant disadvantage in cT1b tumours. Also, RAPN might be the only surgical modality that provides better LRFS than PCA. In cT1 tumours, PCA shows MFS and CSS comparable to PN. Lastly, PCA is associated with a shorter OS than PN. [ABSTRACT FROM AUTHOR]

Simple Summary: Peritoneal metastases have a poor prognosis, and one potential treatment option is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). The specific role of HIPEC is still poorly defined. In this cross-sectional study, we systematically analyzed all HIPEC trials registered on ClinicalTrials.gov to identify current research areas and to provide a perspective on expected outcomes. Only 11% (n = 26) of HIPEC trials registered on ClinicalTrials.gov (n = 234) have been published. The registered trials are very heterogeneous regarding methodological approaches and study designs. Currently, research is being conducted on 20 different drugs. The most studied cancers in HIPEC trials are peritoneal metastatic colorectal tumors, gastric cancer, and ovarian cancer. Introduction: Over the past two decades, cytoreductive surgery and HIPEC has improved outcomes for selected patients with peritoneal metastasis from various origins. This is a cross-sectional study with descriptive analyses of HIPEC trials registered on ClinicalTrials.gov. This study aimed to characterize clinical trials on HIPEC registered on ClinicalTrials.gov with the primary objective of identifying a trial focus and to examine whether trial results were published. Methods: The search included trials registered from 1 January 2001 to 14 March 2022. We examined the associations of exposure variables and other trial features with two primary outcomes: therapeutic focus and results reporting. Results: In total, 234 clinical trials were identified; 26 (11%) were already published, and 15 (6%) trials have reported their results but have not been published as full papers. Among ongoing nonpublished trials, 81 (39%) were randomized, 30 (14%) were blinded, n = 39 (20%) were later phase trials (i.e., phases 3 and 4), n = 152 (73%) were from a single institution, and 91 (44%) had parallel groups. Most of the trials were recruiting at the time of this analysis (75, 36%), and 39 (20%) were completed but had yet to publish results. In total, 68% of the trials focused on treatment strategies, and 53% investigated the oncological outcome. The most studied neoplasms for HIPEC trials were peritoneally metastasized colorectal cancer (32%), gastric cancer (29%), and ovarian cancer (26%). Twenty different drugs were analyzed in these clinical trials. Conclusions: Many study results are awaited from ongoing HIPEC trials. Most HIPEC trials focused on gastric, colorectal, or ovarian cancer. Many clinical trials were identified involving multiple entities and chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Simple Summary: Chordoma is a rare cancer that often occurs at the base of the skull. Treating skull base chordoma is challenging because the tumor is difficult to completely remove with surgery and has low radiosensitivity. This study compared two types of radiation modality: particle beam therapy (PT) and photon radiotherapy (RT). We found that PT provides better progression-free survival compared to photon RT. However, PT also has a higher risk of causing brain necrosis. Our findings suggest that PT is more effective for controlling skull base chordoma, but careful planning is needed to minimize side effects. [Objective] The aim of this study was to compare the efficacy of particle beam therapy (PT) with photon radiotherapy (RT) for treatment of skull base chordoma. [Methods] A systematic review was conducted for skull base chordoma treated with PT or photon RT reported from 1990 to 2022. Data were extracted for overall survival (OS) and progression-free survival (PFS), late adverse events, age, gender, gross total resection (GTR) rates, tumor volume, total irradiation dose, and treatment modality. Random-effects meta-regression analysis with the treatment modality as an explanatory variable was performed for each outcome to compare the modalities. [Results] A meta-analysis of 30 selected articles found 3- and 5-year OS rates for PT vs. photon RT or combined photon RT/proton beam therapy (PBT) of 90.8% (95% CI: 87.4–93.3%) vs. 89.5% (95% CI: 83.0–93.6%), p = 0.6543; 80.0% (95% CI: 75.7–83.6%) vs. 89.5% (95% CI: 83.0–93.6%), p = 0.6787. The 5-year PFS rates for PT vs. photon RT or photon RT/PBT were 67.8% (95% CI: 56.5–76.7%) vs. 40.2% (95% CI: 31.6–48.7%), p = 0.0004. A random-effects model revealed that the treatment modality (PT vs. photon RT or photon RT/PBT) was not a significant factor for 3-year OS (p = 0.42) and 5-year OS (p = 0.11), but was a significant factor for 5-year PFS (p < 0.0001). The rates of brain necrosis were 8–50% after PT and 0–4% after photon RT or photon RT/PBT. [Conclusion] This study shows that PT results in higher PFS compared to photon RT for skull base chordoma, but that there is a tendency for a higher incidence of brain necrosis with PT. Publication and analysis of further studies is needed to validate these findings. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck bone reconstruction with revascularized free periosteal flaps and scaffold is an overlooked option in the literature. Aim of the present paper was to systematically analyse the results of maxillary and mandibular reconstruction with this technique. We found a total of 7 studies with 55 patients fitting with our inclusion criteria. The overall rate of complications was 43.7%. The success rate intended as scaffold integration resulted to be 74.5%. Our paper therefore highlighted that maxillary and mandibular reconstruction with revascularized free periosteal flaps and scaffold is a possible alternative in patient unable to bone free flap complex reconstruction, with a success rate higher to that of other secondary options. Introduction: Head and neck bone reconstruction is a challenging surgical scenario. Although several strategies have been described in the literature, bone free flaps (BFFs) have become the preferred technique for large defects. Revascularized free periosteal flaps (FPFs) with support scaffold represents a possible alternative in compromised patient, BFF failure, or relapsing cancers as salvage treatment. However, only few clinical applications in head and neck are reported in literature. Purpose of the study was to systematically analyse the results of functional and oncologic maxillary and mandibular reconstruction with FPF with scaffold. Materials and Methods: A comprehensive review of the dedicated literature was performed according to the PRISMA guidelines searching on Scopus, PubMed/MEDLINE, Cochrane Library, Embase, Researchgate and Google Scholar databases using relevant keywords, phrases and medical subject headings (MeSH) terms. An excursus on the most valuable FPF' harvesting sites was also carried out. Results: A total of 7 studies with 55 patients were included. Overall, the majority of the patients (n = 54, 98.1%) underwent an FPF reconstruction of the mandibular site. The most used technique was the radial forearm FPF with autologous frozen bone as scaffold (n = 40, 72.7%). The overall rate of complications was 43.7%. The success rate intended as scaffold integration resulted to be 74.5%. Conclusions: Maxillary and mandibular reconstruction with FPF and scaffold is a possible alternative in patient unfit for complex BFF reconstruction and it should be considered as a valid alternative in the sequential salvage surgery for locally advanced cancer. Moreover, it opens future scenarios in head and neck reconstructive surgery, as a promising tool that can be modelled to tailor complex 3D defects, with less morbidities to the donor site. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer continues to be among the most prevalent cancers affecting the female reproductive system. The timely and precise diagnosis of endometrial cancer is crucial for the survival of individuals affected by it. The aim of the present systematic review and meta-analysis was to consolidate and assess the findings concerning the diagnostic precision of frozen section analysis of endometrial tissues for diagnosing endometrial cancer and atypical hyperplasia. The method has demonstrated high reliability in diagnosing endometrial cancer and even greater accuracy for atypical hyperplasia. This could significantly influence clinical practice, as a less invasive procedure such as frozen section biopsy could benefit a substantial number of women. The early and accurate diagnosis of endometrial cancer is of paramount importance for the survival of these patients. The aim of this study was to systematically appraise the available data regarding the accuracy of frozen section biopsy in diagnosing endometrial cancer. A thorough literature search was performed in PubMed/Medline, Scopus and the Cochrane Central Register of Controlled Trials databases from inception up to January 2023, with the use of specific, relevant key terms. A quality evaluation for each study was performed with the QUADAS-2 tool, whereas a bivariate random-effect model was performed to generate a summary receiver-operated curve. Heterogeneity was evaluated with Cochrane Q and Higgins' I2 statistics. Subgroup analyses were performed for studies focused on atypical hyperplasia and those focused on endometrial cancer. The search yielded 47 studies, involving 7790 patients with endometrial cancer. Among them, only 11 could be included in the quantitative analysis. QUADAS-2 evaluation resulted in rather high quality among the included studies. Quantitative synthesis resulted in a pooled sensitivity of 0.863 and pooled specificity of 0.916. The AUC was 0.948, the Q statistic was 10.488 (10 df, p = 0.399) and Higgins' I2 (4.655%) reported no significant heterogeneity. Subgroup analyses based on the diagnosis revealed a pooled sensitivity 0.886, specificity 0.862 and AUC 0.934 for endometrial cancer versus a sensitivity of 0.816, specificity of 0.962 and AUC 0.939 for atypical hyperplasia. Frozen section appears as a valid and reliable diagnostic tool for endometrial cancer. Its reliability seems to be even higher for the diagnosis of atypical hyperplasia. Therefore, this method may be considered in clinical practice and in settings with appropriate resources. [ABSTRACT FROM AUTHOR]

Simple Summary: There is little evidence about the optimal timing of systemic chemotherapy (SC) in patients treated with cytoreductive surgery (CRS) and HIPEC for colorectal peritoneal metastases (CRC-PM). Due to the lack of evidence in this field, a systematic literature search and a meta-analysis of relevant studies were performed. Twenty-one studies were included in the systematic review and fifteen in the quantitative analysis (4523 patients). Postoperative SC was associated with increased overall survival compared to no SC or a preoperative SC regimen, whereas SC (pre or post) and pre-SC compared to surgery alone were not. Similar results were found for disease-free survival. Preoperative SC was not associated with an increased risk of severe surgical complications. Background. For patients with colorectal cancer (CRC) peritoneal metastases (PM) who are eligible for cytoreductive surgery (CRS), the indication and timing of systemic chemotherapy (SC) are still under debate. This study aims to analyze the role of pre, post or perioperative SC on the survival and surgical complications of patients treated with CRS-HIPEC. Methods. After a systematic search in MEDLINE, Cochrane Database of Systematic Reviews, Scopus, Web of Science and Embase, a meta-analysis was performed to compare postoperative complications, disease-free survival (DFS) and overall survival (OS) according to SC administration and timing. PROSPERO: CRD42023478977. Results. Of 1203 studies screened, 15 were included in the meta-analysis (4523 patients). Post-operative SC was associated with increased overall survival (post-SC vs. no post-SC: HR 0.81, p = 0.00001, I2 = 0%; pre-SC vs. post-SC: HR 0.65, p = 0.01, I2 = 28%), whereas SC (pre or post) or pre-SC compared to surgery alone was not (SC vs. no SC: p = 0.29, I2 = 80%; pre-SC vs. no pre-SC: p = 0.59, I2 = 58%). Similar results were seen for DFS. SC was not associated with an increased complication rate (p = 0.47, I2 = 64%). Conclusions. Systemic chemotherapy administration in patients undergoing radical surgery for colorectal peritoneal metastases is associated with increased survival only in the adjuvant/post-operative setting. Considering the limitations of the included studies, further trials are needed to answer this unresolved question. [ABSTRACT FROM AUTHOR]

Simple Summary: Local recurrence is a significant issue for advanced gastric cancer patients. Complete mesogastric excision (CME) has been advocated to enhance lymph node (LN) retrieval and reduce recurrence rates. A systematic review of the literature was conducted according to the Cochrane recommendations, and meta-analyses of means and binary outcomes were developed. The number of lymph nodes retrieved was the primary endpoint, with other postoperative outcomes as secondary. Thirteen studies were included, showing that the mean number of harvested LNs was significantly higher among patients undergoing CME. CME patients also had significantly lower intraoperative blood loss, a shorter length of stay, and a shorter operative time. Radical gastrectomy with CME may provide a safe and more radical lymphadenectomy. Long-term outcomes and the applicability of this technique in the West are still to be proven. Complete mesogastric excision (CME) has been advocated to allow for a more extensive retrieval of lymph nodes, as well as lowering loco-regional recurrence rates. This study aims to analyze the short-term outcomes of D2 radical gastrectomy with CME compared to standard D2 gastrectomy. A systematic review of the literature was conducted according to the Cochrane recommendations until 2 July 2023 (PROSPERO ID: CRD42023443361). The primary outcome, expressed as mean difference (MD) and 95% confidence intervals (CI), was the number of harvested lymph nodes (LNs). Meta-analyses of means and binary outcomes were developed using random effects models to assess heterogeneity. The risk of bias in included studies was assessed with the RoB 2 and ROBINS-I tools. There were 13 studies involving 2009 patients that were included, revealing a significantly higher mean number of harvested LNs in the CME group (MD: 2.55; 95% CI: 0.25–4.86; 95%; p = 0.033). The CME group also experienced significantly lower intraoperative blood loss, a lower length of stay, and a shorter operative time. Three studies showed a serious risk of bias, and between-study heterogeneity was mostly moderate or high. Radical gastrectomy with CME may offer a safe and more radical lymphadenectomy, but long-term outcomes and the applicability of this technique in the West are still to be proven. [ABSTRACT FROM AUTHOR]

Simple Summary: The main treatment for extramammary Paget's disease (EMPD) is still surgery, but this neoplasm usually spreads beyond the clinical surroundings of the lesion, and achieving histopathologically free margins can be challenging and requires mutilating surgery. Moreover, the recurrence rate of the disease is high, reflecting its multifocal nature. Topical immunotherapy could be an alternative treatment for EMPD. The aim of this systematic review was to assess the effectiveness of topical imiquimod in the clinical response of EMPD patients and to describe the management of topical imiquimod in EMPD. Learning about non-surgical treatments such as topical imiquimod can help clinicians manage EMPD and find a balance between disease resolution and treatment morbidity. Extramammary Paget's disease (EMPD) is subclinical in extent and multifocal in nature. There is no global consensus for treatment, so its management represents a challenge in clinical practice. Therefore, we conducted a systematic review through the main electronic databases to assess the effectiveness of topical imiquimod in cutaneous EMPD and to discuss its management. Finally, 24 studies involving a total of 233 EMPD patients treated with topical imiquimod were selected. The topical imiquimod response rate was 67%, and the complete response (CR) rate was 48%. Patients were treated with a three–four times a week regimen in most cases, ranging between 2 to 52 weeks. In addition, imiquimod was applied as an adjunctive treatment in 21 patients, achieving a CR rate of 71%. Consequently, imiquimod therapy could achieve a good response ratio as a first-line treatment, as adjuvant and neo-adjuvant therapy, and as a treatment for recurrent disease. The heterogeneity between studies and the lack of a control arm made it impossible to conduct a meta-analysis. To improve the quality of evidence on EMPD, multicenter studies are essential to collect a larger number of patients and, consequently, obtain high-quality evidence to standardize treatment. The Prospero registration number is CRD42023447443. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic adenocarcinoma is the fourth leading cause of cancer-related death in industrialized countries. In locally advanced and borderline resectable pancreatic cancer, neoadjuvant therapy (NAT) has been shown to be effective in eliminating potentially circulating tumor cells and distant micrometastases, shrinking local tumors, and identifying high-grade malignancies that do not benefit from surgery. However, in patients with resectable pancreatic adenocarcinoma, who represent 20% of new diagnoses and for whom US followed by adjuvant chemotherapy is the standard of care, NAT is controversial because it carries several potential drawbacks that may prevent surgery and increase the risk of clinical deterioration. Randomized clinical trials, retrospective studies, and a few systematic reviews and meta-analyses reported controversial results, and although the safety and feasibility of such an approach are supported, a wider implementation is still a matter of debate. Considering the different methodological approaches (RCTs vs. retrospective studies), the difficulty in providing high-quality evidence due to small patient numbers, and the emergence of new evidence, an update of the current evidence seems essential to help clinicians and researchers understand the role of NAT and offer a new potentially beneficial treatment approach. Thus, the aim of this systematic review and meta-analysis is to evaluate the role of NAT in prolonging overall survival and disease-free survival and improving R0 and N0 rates compared with upfront resection in patients with resectable pancreatic cancer. Background: Despite advances in treatment, the prognosis of resectable pancreatic adenocarcinoma remains poor. Neoadjuvant therapy (NAT) has gained great interest in hopes of improving survival. However, the results of available studies based on different treatment approaches, such as chemotherapy and chemoradiotherapy, showed contrasting results. The aim of this systematic review and meta-analysis is to clarify the benefit of NAT compared to upfront surgery (US) in primarily resectable pancreatic adenocarcinoma. Methods: A PRISMA literature review identified 139 studies, of which 15 were finally included in the systematic review and meta-analysis. All data from eligible articles was summarized in a systematic summary and then used for the meta-analysis. Specifically, we used HR for OS and DFS and risk estimates (odds ratios) for the R0 resection rate and the N+ rate. The risk of bias was correctly assessed according to the nature of the studies included. Results: From the pooled HRs, OS for NAT patients was better, with an HR for death of 0.80 (95% CI: 0.72–0.90) at a significance level of less than 1%. In the sub-group analysis, no difference was found between patients treated with chemoradiotherapy or chemotherapy exclusively. The meta-analysis of seven studies that reported DFS for NAT resulted in a pooled HR for progression of 0.66 (95% CI: 0.56–0.79) with a significance level of less than 1%. A significantly lower risk of positive lymph nodes (OR: 0.45; 95% CI: 0.32–0.63) and an improved R0 resection rate (OR: 1.70; 95% CI: 1.23–2.36) were also found in patients treated with NAT, despite high heterogeneity. Conclusions: NAT is associated with improved survival for patients with resectable pancreatic adenocarcinoma; however, the optimal treatment strategy has yet to be defined, and further studies are required. [ABSTRACT FROM AUTHOR]

Simple Summary: The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway controls the induction and maintenance of immune tolerance within the tumor microenvironment. Hence, immunotherapy is an exciting approach, and tremendous strides have recently been made in our perception of the role of the host immune response in affecting tumor growth and response to various therapies, including in endometrial cancer. Clinical trials investigating PD-1/PD-L1 inhibitors have shown promising results in other cancers, but their efficacy in EC remains uncertain, and guidelines must be consistent. Therefore, this meta-analysis aims to provide a robust analysis of the effectiveness and safety of PD-1/PDL1 inhibitor as single-agent immunotherapy in EC, focusing on three major components: objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Based on the subgroup analysis of mismatch repair (MMR) status, PD-1/PD-L1 inhibitor immunotherapy showed significantly better efficacy in MMR-deficient patients, in terms of both ORR and DCR. The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway plays a crucial role in the immune escape mechanism and growth of cancer cells in endometrial cancer (EC). Clinical trials investigating PD-1/PD-L1 inhibitor have shown promising results in other cancers, but their efficacy in EC still remains uncertain. Therefore, this meta-analysis aims to provide an updated and robust analysis of the effectiveness and safety of PD-1/PDL1 inhibitor as single-agent immunotherapy in EC, focusing on the objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). This meta-analysis utilized STATA version 17 and RevMan version 5.4 software to pool the results of relevant studies. Five studies conducted between 2017 and 2022, comprising a total of 480 EC patients enrolled for PD-1/PD-L1 inhibitor immunotherapy met the inclusion criteria. The pooled proportion of EC patients who achieved ORR through PD-1/PD-L1 inhibitor treatment was 26.0% (95% CI: 16.0–36.0%; p < 0.05). Subgroup analysis based on mismatch repair (MMR) status showed an ORR of 44.0% (95% CI: 38.0–50.0%; p = 0.32) for the deficient mismatch repair (dMMR) group and 8.0% (95% CI: 0.0–16.0%; p = 0.07) for the proficient mismatch repair (pMMR) group. Pooled proportion analysis by DCR demonstrated an odds ratio (OR) of 41.0% (95% CI: 36.0–46.0%, p = 0.83) for patients undergoing PD-1/PD-L1 inhibitor treatment. Subgroup analysis based on MMR status revealed DCR of 54.0% (95% CI: 47.0–62.0%; p = 0.83) for the dMMR group, and 31.0% (95% CI: 25.0–39.0%; p = 0.14) for the pMMR group. The efficacy of PD-1/PD-L1 inhibitors was significantly higher in the dMMR group compared to the pMMR group, in terms of both ORR (OR = 6.30; 95% CI = 3.60–11.03; p < 0.05) and DCR (OR = 2.57; 95% CI = 1.66–3.99; p < 0.05). In terms of safety issues, the pooled proportion of patients experiencing at least one adverse event was 69.0% (95% CI: 65.0–73.0%; p > 0.05), with grade three or higher AEs occurring in 16.0% of cases (95% CI: 12.0–19.0%; p > 0.05). Based on the subgroup analysis of MMR status, PD-1/PD-L1 inhibitor immunotherapy showed significantly better efficacy among dMMR patients. These findings suggest that patients with dMMR status may be more suitable for this treatment approach. However, further research on PD-1/PD-L1 inhibitor immunotherapy strategies is needed to fully explore their potential and improve treatment outcomes in EC. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastric cancer with metastasis to the peritoneum carries a poor prognosis, with a 40% mortality rate. The optimal treatment modalities have not been established for gastric cancer patients with peritoneal carcinomatosis (GC/PC). We have conducted a systematic review and meta-analysis of available studies on novel treatment strategies including HIPEC and PIPAC to evaluate their safety and efficacy. Through this, our study contextualizes their role in the current treatment pathways for advanced gastric cancer. Background: Gastric cancer has a poor prognosis and involves metastasis to the peritoneum in over 40% of patients. The optimal treatment modalities have not been established for gastric cancer patients with peritoneal carcinomatosis (GC/PC). Although studies have reported favourable prognostic factors, these have yet to be incorporated into treatment guidelines. Hence, our review aims to appraise the latest diagnostic and treatment developments in managing GC/PC. Methods: A systematic review of the literature was performed using MEDLINE, EMBASE, the Cochrane Review, and Scopus databases. Articles were evaluated for the use of hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurised intraperitoneal aerosolised chemotherapy (PIPAC) in GC/PC. A meta-analysis of studies reporting on overall survival (OS) in HIPEC and comparing the extent of cytoreduction as a prognostic factor was also carried out. Results: The database search yielded a total of 2297 studies. Seventeen studies were included in the qualitative and quantitative analyses. Eight studies reported the short-term OS at 1 year as the primary outcome measure, and our analysis showed a significantly higher OS for the HIPEC/CRS cohort compared to the CRS cohort (pooled OR = 0.53; p = 0.0005). This effect persisted longer term at five years as well (pooled OR = 0.52; p < 0.0001). HIPEC and CRS also showed a longer median OS compared to CRS (pooled SMD = 0.61; p < 0.00001). Three studies reporting on PIPAC demonstrated a pooled OS of 10.3 (2.2) months. Prognostic factors for longer OS include a more complete cytoreduction (pooled OR = 5.35; p < 0.00001), which correlated with a peritoneal carcinomatosis index below 7. Conclusions: Novel treatment strategies, such as HIPEC and PIPAC, are promising in the management of GC/PC. Further work is necessary to define their role within the treatment algorithm and identify relevant prognostic factors that will assist patient selection. [ABSTRACT FROM AUTHOR]

Simple Summary: To date, quantitative and comprehensive information summarizing the differences in the efficacy and safety of anti-CD19 chimeric antigen receptor (CAR) T-cells with CD28 co-stimulatory domains or 4-1BB co-stimulatory domains for the treatment of B-cell acute lymphoblastic leukemia (B-ALL) is lacking. Our study utilized a model-based meta-analysis (MBMA) to accurately measure the differences between the anti-CD19 CAR T-cell therapies for B-ALL with CD28 and 4-1BB co-stimulatory domains. We discovered that the median overall survival (OS) and progression-free survival (PFS) for the 4-1BB co-stimulatory domain were longer than those for anti-CD19 CAR T-cell therapy with a CD28 co-stimulatory domain. Additionally, anti-CD19 CAR T-cells with the CD28 co-stimulatory domain showed a higher incidence of neurotoxic adverse effects. This study provides quantitative information that can be used to compare the different co-stimulatory domains of anti-CD19 CAR T-cells for treating B-ALL. This study quantified the differences in the efficacy and safety of different stimulation domains of anti-CD19 chimeric antigen receptor (CAR) T therapy for B-cell acute lymphoblastic leukemia (B-ALL). Clinical trials related to anti-CD19 CAR T-cell therapy for B-ALL were searched in public databases from database inception to 13 November 2021. The differences in overall survival (OS) and progression-free survival (PFS) of B-ALL patients treated with anti-CAR T-cell therapy containing 4-1BB and CD28 co-stimulatory domains were compared by establishing a parametric survival function. The overall remission rate (ORR), the proportion of people with minimal residual disease (MRD)-negative complete remission (CR), the incidence of cytokine release syndrome (CRS), and the neurotoxicity across different co-stimulatory domains was assessed using a random-effects model. The correlation between the ORR, MRD-negative CR, PFS, and OS was tested. The results showed that the median OS of anti-CAR T-cell treatment containing 4-1BB and CD28 co-stimulatory domains was 15.0 months (95% CI: 11.0–20.0) and 8.5 months (95% CI: 5.0–14.0), and the median PFS was 7.0 months (95% CI: 4.0–11.5) and 3.0 months (95% CI: 1.5–7.0), respectively. Anti-CD19 CAR T-cells in the 4-1BB co-stimulatory domain showed superior benefits in patients who achieved ORR. The incidence of neurotoxicity was significantly higher in the CD28 co-stimulatory domain of anti-CD19 CAR T-cells than in the 4-1BB co-stimulatory domain. In addition, the ORR and MRD-negative CR were strongly correlated with OS and PFS, and PFS and OS were strongly correlated. The 4-1BB co-stimulatory domain suggested a better benefit–risk ratio than the CD28 co-stimulatory domain in B-ALL. [ABSTRACT FROM AUTHOR]

Simple Summary: Taking into consideration the high risk of patients with cancer for severe COVID-19 infection, prioritization has been given to primary prevention with both primary and booster vaccination. However, robust evidence for vaccination efficacy remains limited, due to the lack of available clinical trials including patients with active cancer. The rates of both humoral and cellular immune response remain rather vague, and they are mainly based on data deriving from retrospective studies of limited internal and external validity. We aimed to gather and analyze the current available literature on the efficacy of COVID-19 vaccination among patients with different types of malignancies receiving different treatments. Our results highlight that patients with cancer present suboptimal immune responses after COVID-19 vaccination, which is more prominent among patients with hematological malignancies. The exclusion of patients with cancer in clinical trials evaluating COVID-19 vaccine efficacy and safety, in combination with the high rate of severe infections, highlights the need for optimizing vaccination strategies. The aim of this study was to perform a systematic review and meta-analysis of the published available data from prospective and retrospective cohort studies that included patients with either solid or hematological malignancies according to the PRISMA Guidelines. A literature search was performed in the following databases: Medline (Pubmed), Scopus, Clinicaltrials.gov, EMBASE, CENTRAL and Google Scholar. Overall, 70 studies were included for the first and second vaccine dose and 60 studies for the third dose. The Effect Size (ES) of the seroconversion rate after the first dose was 0.41 (95%CI: 0.33–0.50) for hematological malignancies and 0.56 (95%CI: 0.47–0.64) for solid tumors. The seroconversion rates after the second dose were 0.62 (95%CI: 0.57–0.67) for hematological malignancies and 0.88 (95%CI: 0.82–0.93) for solid tumors. After the third dose, the ES for seroconversion was estimated at 0.63 (95%CI: 0.54–0.72) for hematological cancer and 0.88 (95%CI: 0.75–0.97) for solid tumors. A subgroup analysis was performed to evaluate potential factors affecting immune response. Production of anti-SARS-CoV-2 antibodies was found to be more affected in patients with hematological malignancies, which was attributed to the type of malignancy and treatment with monoclonal antibodies according to the subgroup analyses. Overall, this study highlights that patients with cancer present suboptimal humoral responses after COVID-19 vaccination. Several factors including timing of vaccination in relevance with active therapy, type of therapy, and type of cancer should be considered throughout the immunization process. [ABSTRACT FROM AUTHOR]

Simple Summary: Patient-Reported Outcome Measures (PROMs) provide reports from patients on their own health, quality of life, or functional status associated with their disease, and the care they have received. In treating metastatic colorectal cancer (CRC), it is important to obtain information about the impact of a treatment on various aspects of patients' lives besides overall survival. We performed a review on the use of PROMs in phase III clinical trials started between 2010 and 2021, evaluating systemic therapy in patients with metastatic CRC. We demonstrate that the quality of reporting on PROMs has increased over the last decade, but is still not optimal. Moreover, PROM results are underreported in studies on metastatic CRC, impeding the optimal incorporation of trial and PROM results into daily clinical practice. Purpose: To perform a scoping review on the use of Patient-Reported Outcome Measures (PROMs) in randomized trials on systemic therapy in patients with metastatic colorectal cancer (mCRC) between 2010 and 2021. Methods: First, a search on clinicaltrials.gov was performed, looking for randomized trials in mCRC. The use of PROMs was analyzed quantitatively. Subsequently, we assessed the completeness of PROM reporting based on the CONSORT PRO extension in publications related to the selected trials acquired using Embase and PubMed. Results: A total of 46/176 trials were registered on clinicaltrials.gov used PROMs. All these trials used validated PROM instruments. The EORTC QLQ-C30 was most frequently used (37 times), followed by the EQ-5D (21 times) and the EORTC QLQ-CR29 (six times). A total of 56/176 registered trials were published. In 35% (n = 20), the results of the PROMs were available. Overall, 7/20 (35%) trials documented all items of the CONSORT PRO extension and quality of reporting according to the CONSORT PRO extension was higher than in the period 2004–2012. In 3/20 (15%) of the published trials, the results of PROMs were not discussed nor included in the positioning of the new treatment compared to the reference treatment. Conclusion: When PROMs are used, the quality of reporting on patient-reported outcomes is improving, but this must continue in order to optimize the translation of trial results to individual patient values. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) is one of the most malignant tumors. Immune checkpoint inhibitors (ICIs)-based therapy has recently been demonstrated to greatly ameliorate survival outcomes in advanced HCC. The objective of this research was to evaluate clinical outcomes of ICIs-based monotherapy and combination therapy as first-line treatment of adults with advanced HCC in real-world practice by conducting a systematic literature review and meta-analysis. These findings could supplement the evidence for treatment strategies of advanced HCC and inform study design in future real-world studies of HCC. Background: Immune checkpoint inhibitors (ICIs)-based therapy has recently been demonstrated to greatly ameliorate survival outcomes in advanced hepatocellular carcinoma (HCC). We aimed to evaluate clinical outcomes of ICIs-based monotherapy and combination therapy as first-line treatment of adults with advanced HCC in real-world practice by conducting a systematic literature review and meta-analysis. Methods: PubMed, Web of Science, and Embase were searched up to 25 April 2022. Retrospective or prospective real-world studies evaluating progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs) of patients with advanced HCC receiving first-line ICIs-based therapy were included. Results: Of 7805 studies retrieved, 38 were deemed eligible for inclusion. For patients receiving first-line ICIs-based therapy in real-world practice, the pooled median PFS and OS were 7.03 (95% CI: 5.55–8.51) and 14.39 (95% CI: 10.91–17.86) months. The ORR and DCR were 0.432 (95% CI: 0.327–0.538) and 0.756 (95% CI: 0.677–0.836), according to mRECIST 1.1, 0.317 (95% CI: 0.218–0.416) and 0.740 (95% CI: 0.644–0.835), judged by RECIST 1.1. The best outcomes of survival and response rate were observed in ICIs-based combination therapy of ICIs, TKIs, plus LRTs. Furthermore, ORR, DCR judged by mRECIST 1.1, and PFS could be potential prognostic factors for OS. Conclusions: This research revealed diversified first-line ICIs-based therapies for advanced HCC in real-world practice. Future studies are needed to adopt prospective, multicentric and comparative designs to test the ICIs-based combination therapies, especially triple therapies of ICIs, TKIs, plus LRTs. [ABSTRACT FROM AUTHOR]

Simple Summary: Given the low prevalence and the heterogeneity of childhood cancers, information about the safety of anti-angiogenic drugs in pediatric patients is only partially assessed. We aimed to evaluate the safety of these drugs in children with solid tumors. This systematic review and meta-analysis reported that one out of two pediatric patients using anti-angiogenic drugs in monotherapy experienced a serious adverse event despite proportions varying per single drug. Cancer is a clinical condition that can benefit from anti-angiogenic drugs (AADs). Given the low prevalence and the heterogeneity of childhood cancers, information about the safety of these drugs in pediatric patients is partially assessed. The aim of this study was to evaluate the safety of AADs in pediatric patients with solid tumors. Clinical trials and observational studies were searched in PubMed, ISI Web of Science, and ClinicalTrials database For each included study, adverse events (AEs) were extracted. A meta-analysis was conducted by pooling proportions of AEs using a random intercept logistic regression model. Seventy studies were retrieved. Most part were clinical trials (55 out of 70), and only fifteen observational studies were found. Overall, proportion of serious and non-serious AEs of AADs used as monotherapy was 46% and 89%, respectively. Proportions of serious AEs varied among drugs: sunitinib, 79%; lenvatinib, 64%; sorafenib, 48%; ramucirumab, 41%; pazopanib, 30%; and vandetanib, 27%. A higher proportion of non-serious hematological AEs was found in the patients receiving pazopanib with respect to sunitinib and lenvatinib. The safety profile of AADs has been extensively investigated for mostly drugs in phase I and II trials and is limited to acute toxicities. Overall, one out of two patients using AAD drugs in monotherapy experienced a serious AE despite proportions varied per single drugs. When AADs were combined with standard chemotherapy, the proportion of AEs varied in relation to the single combinations. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is a growing problem in modern society and is one of the most prevalent cancers among women. Oncologic breast surgery has become an effective therapeutic modality but is often accompanied by major physical and moral impacts on patients. Implant-based reconstruction helps to restore quality of life and aims at providing an optimal esthetic recovery, although the question of implant placement has been too poorly assessed in the past years. In this meta-analysis, we collected and analyzed existing evidence on postoperative outcomes following prepectoral and subpectoral breast reconstruction and allowed us to provide one of the largest pools of patients on this topic. We observed globally higher pain scores following subpectoral implants; however, the rates of postoperative complications remained comparable in a pooled analysis. The risks and benefits of each procedure should be discussed with the patient prior to surgery, and decision making should be guided by surgical expertise. (1) Background: Implant-based breast reconstruction following mastectomy helps to restore quality of life while aiming at providing optimal cosmetic outcomes. Both prepectoral (PP) and subpectoral (SP) breast implants are widely used to fulfill these objectives. It is, however, unclear which approach offers stronger postoperative benefits. (2) Methods: We performed a systematic review of the literature through PubMed, Cochrane Library, and ResearchGate, following the PRISMA guidelines. Quantitative analysis for postoperative pain as the primary outcome was conducted. Secondary outcomes included patient satisfaction and postoperative complications such as seroma, implant loss, skin necrosis, wound infection, and hematoma. (3) Results: Nine articles involving 1119 patients were retrieved. Our results suggested increased postoperative pain after SP implants and significantly higher rates of seroma following PP implants (p < 0.05). Patient satisfaction was found to be similar between the two groups; however, the heterogeneity of measurement tools did not allow us to pool these results. The rates of implant loss, skin necrosis, wound infection, and hematoma showed no significant differences between the two cohorts. (4) Conclusion: Our data suggest that both implant placements are safe and effective methods for breast reconstruction following mastectomy. However, homogeneity in outcome measurements would allow one to provide stronger statistical results. [ABSTRACT FROM AUTHOR]

Simple Summary: Many individuals with cancer suffer from persistent exhaustion due to cancer therapy, known as cancer-related fatigue (CRF). Yoga, psychosocial, and mindfulness-based interventions are recommended to reduce CRF. However, it is not clear yet how interventions need to be designed to maximize their efficacy. This meta-analysis aimed to identify intervention characteristics associated with greater reductions in CRF. A total of 70 interventions with 6387 participants were included in the analysis. Our results found a positive effect of yoga, psychosocial, and mindfulness-based interventions, while all invention types revealed large differences in intervention effects. In psychosocial interventions, using a group setting and working on cognition was related to higher efficacy. Regarding yoga and mindfulness-based interventions, no specific intervention characteristics emerged as more favorable than others. Overall, this meta-analysis suggests opportunities to optimize psychosocial interventions for CRF, whereas the design of yoga and mindfulness-based interventions seems to allow for variation. Cancer-related fatigue (CRF) is a burdensome sequela of cancer treatments. Besides exercise, recommended therapies for CRF include yoga, psychosocial, and mindfulness-based interventions. However, interventions conducted vary widely, and not all show a significant effect. This meta-analysis aimed to explore intervention characteristics related to greater reductions in CRF. We included randomized controlled trials published before October 2021. Standardized mean differences were used to assess intervention efficacy for CRF and multimodel inference to explore intervention characteristics associated with higher efficacy. For the meta-analysis, we included 70 interventions (24 yoga interventions, 31 psychosocial interventions, and 15 mindfulness-based interventions) with 6387 participants. The results showed a significant effect of yoga, psychosocial, and mindfulness-based interventions on CRF but with high heterogeneity between studies. For yoga and mindfulness-based interventions, no particular intervention characteristic was identified to be advantageous for reducing CRF. Regarding psychosocial interventions, a group setting and work on cognition were related to higher intervention effects on CRF. The results of this meta-analysis suggest options to maximize the intervention effects of psychosocial interventions for CRF. The effects of yoga and mindfulness-based interventions for CRF appear to be independent of their design, although the limited number of studies points to the need for further research. [ABSTRACT FROM AUTHOR]

Simple Summary: The rapid spread of the new Coronavirus-19 disease (COVID-19) has led to the implementation of unprecedented confinement measures, while healthcare systems were restructured in order to confront the pandemic; these radical measures have prevented people from seeking medical advice. At the same time, oncology and surgery societies altered treatment guidelines, favoring postponement of surgery. The aim of the present study is to determine the impact of the pandemic in the management of colorectal cancer patients. We confirmed that during the pandemic, patients were more likely to present with metastatic cancer, often requiring emergent or palliative interventions. In addition, neoadjuvant therapy and conventional open surgery utilization rates were increased in the pandemic era. These observed changes in clinical practice may be associated with tumor upstaging, which carries significant implications regarding the long-term oncologic survival of patients with colorectal neoplasias. (1) Background: To determine the impact of the COVID-19 pandemic in the management of colorectal cancer patients requiring surgery and to examine whether the restructuring of healthcare systems led to cancer stage upshifting or adverse treatment outcomes; (2) Methods: A systematic literature search of the MedLine, Scopus, Web of Science, and CNKI databases was performed (PROSPERO ID: CRD42021288432). Data were summarized as odds ratios (OR) or weighted mean differences (WMDs) with 95% confidence intervals (95% CIs); (3) Results: Ten studies were examined, including 26,808 patients. The number of patients presenting with metastases during the pandemic was significantly increased (OR 1.65, 95% CI 1.02–2.67, p = 0.04), with no differences regarding the extent of the primary tumor (T) and nodal (N) status. Patients were more likely to have undergone neoadjuvant therapy (OR 1.22, 95% CI 1.09–1.37, p < 0.001), while emergency presentations (OR 1.74, 95% CI 1.07–2.84, p = 0.03) and palliative surgeries (OR 1.95, 95% CI 1.13–3.36, p = 0.02) were more frequent during the pandemic. There was no significant difference recorded in terms of postoperative morbidity; (4) Conclusions: Patients during the pandemic were more likely to undergo palliative interventions or receive neoadjuvant treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the large use of inhibitors of Poly-ADP ribose polymerase (PARP-I), the feasibility and safety of their combination with radiotherapy (RT) are unclear. The combination may be particularly interesting in the oligometastatic setting in which patients may benefit from local RT during the treatment with PARP-I. The aim of the current review was to evaluate the outcome and the toxicity in patients with newly diagnosed or recurrent tumors treated with a combination of PARP-I and RT. A total of 12 clinical studies met the inclusion criteria and, despite the heterogeneity of the evaluated patient populations and tumor types, this review suggests that a combination approach is feasible even though the efficacy profile remains unclear. Background: Despite the large use of inhibitors of Poly-ADP ribose polymerase (PARP-I), the feasibility and safety of their combination with radiotherapy (RT) is unclear. Aim: We conducted a literature analysis with the aim to evaluate the efficacy and safety profile of a combination with RT and PARP-I. Method: The key issues for the current review were expressed in two questions according to the Population, Intervention, Control, Outcome (PICO) criteria: 1. What is the outcome and 2. What is the toxicity in patients treated with a combination of PARP-I and RT for a newly diagnosed or recurrent tumors? Results: A total of 12 clinical studies met the inclusion criteria including seven single-arm dose-escalation phase I studies, two phase II (two- and three-arms controlled trials) trials, one parallel-arm phase I study, and two phase I/II studies published between 2015 and 2021. RT was performed with photon beams and several schedules according to the clinical situation. The acute toxicity ≥ grade 3 ranged between 25% and >96%, which was divided into hematological or non-hematological adverse events. Conclusions: despite the heterogeneity of the evaluated patient populations and tumor types, and the limited number of the studies, this review suggests that a combination approach is feasible even though the efficacy profile remains unclear. [ABSTRACT FROM AUTHOR]

Simple Summary: Favorable survival outcomes for patients with advanced-stage ovarian cancer are associated with complete cytoreduction. Enlarged cardiophrenic lymph node (CPLN) is commonly observed in advanced-stage epithelial ovarian cancer (AEOC); however, the prognostic impact of CPLN adenopathy is inconclusive. In this study, we evaluate the clinical outcomes of CPLN adenopathy in AEOC patients who underwent cytoreductive surgery. This systematic review and meta-analysis demonstrated that enlarged CPLN in preoperative imaging is highly associated with metastatic involvement. Patients with CPLN adenopathy had a significantly increased risk of recurrence of disease and dying from the disease in comparison to those without adenopathy, a finding likely related to more advanced disease in this group. Currently, there are no data that definitively demonstrate a therapeutic benefit of CPLN resection. Further randomized controlled trials should be conducted to definitively demonstrate whether CPLN resection at the time of cytoreductive surgery is beneficial. Purpose: To evaluate the clinical outcomes of enlarged cardiophrenic lymph node (CPLN) in advanced-stage epithelial ovarian cancer (AEOC) patients who underwent cytoreductive surgery. Methods: The Embase, Medline, Web of Science, Cochrane Library, and Google Scholar databases were searched for articles from the database inception to June 2021. Meta-analysis was conducted to determine the prognostic impact of surgical outcome, postoperative complication, and survival using random-effects models. Results: A total of 15 studies involving 727 patients with CPLN adenopathy and 981 patients without CPLN adenopathy were included. The mean size of preoperative CPLN was 9.1± 3.75 mm. Overall, 82 percent of the resected CPLN were histologically confirmed pathologic nodes. Surgical outcomes and perioperative complications did not differ between both groups. The median OS time was 42.7 months (95% CI 10.8–74.6) vs. 47.3 months (95% CI 23.2–71.2), in patients with and without CPLN adenopathy, respectively. At 5 years, patients with CPLN adenopathy had a significantly increased risk of disease recurrence (HR 2.14, 95% CI 1.82–2.52, p < 0.001) and dying from the disease (HR 1.74, 95% CI 1.06–2.86, p = 0.029), compared with those without CPLN adenopathy. CPLN adenopathy was significantly associated with ascites (OR 3.30, 95% CI 1.90–5.72, p < 0.001), pleural metastasis (OR 2.58, 95% CI 1.37–4.82, p = 0.003), abdominal adenopathy (OR 2.30, 95% CI 1.53–3.46, p < 0.001) and extra-abdominal metastasis (OR 2.30, 95% CI 1.61–6.67, p = 0.001). Conclusions: Enlarged CPLN in preoperative imaging is highly associated with metastatic involvement. Patients with CPLN adenopathy had a lower survival rate, compared with patients without CPLN adenopathy. Further randomized controlled trials should be conducted to definitively demonstrate whether CPLN resection at the time of cytoreductive surgery is beneficial. [ABSTRACT FROM AUTHOR]

Simple Summary: The benefit of programmed death-1/programmed death ligand-1 (PD-1/PD-L1) immunotherapy, particularly of nivolumab, pembrolizumab and atezolizumab, in the second-line setting of patients with non-small cell lung cancer has been documented in randomized clinical trials, showing improvements in global survival and in the overall response rate. Nevertheless, patients enrolled in these studies met strict eligibility criteria, allowing for the treatment of patients that do not reflect the broader oncology patient population. Experiences from real-world data are useful in providing further evidence of the benefit of treatment in a wider range of patients, including those underrepresented in clinical trials. We performed a meta-analysis to evaluate the outcomes in non-small cell lung cancer patients treated in everyday practice with these drugs as the second line, and more generally with immunotherapy with checkpoint inhibitors (ICIs), showing that the efficacy and safety were comparable to those in selected studies. Results may encourage to treat patients excluded from randomized studies. Immunotherapy based on anti PD-1/PD-L1 inhibitors is the new standard of advanced non-small cell lung cancers. Pembrolizumab, nivolumab and atezolizumab are used in clinical practice. The strict eligibility criteria of clinical trials do not allow researchers to fully represent treatment effects in the patients that will ultimately use these drugs. We performed a systematic review and a meta-analysis to evaluate the effectiveness and safety of these drugs, and more generally of ICIs, as second-line therapy in NSCLC patients in real world practice. MEDLINE, PubMed, Scopus and Web of Science were searched to include original studies published between January 2015 and April 2020. A total of 32 studies was included in the meta-analysis. The overall radiological response rate (ORR), disease control rate (DCR), median progression-free survival (PFS) and overall survival (OS) were 21%, 52%, 3.35 months and 9.98 months, respectively. The results did not change when analysis was adjusted for Eastern Cooperative Oncology Group performance status (ECOG PS) and age. A unitary increase in the percent of patients with liver and CNS metastases reduced the occurrence of DCR by 7% (p < 0.001) and the median PFS by 2% (p = 0.010), respectively. The meta-analysis showed that the efficacy and safety of immunotherapy in everyday practice is comparable to that in clinical trials. [ABSTRACT FROM AUTHOR]

Immunotherapy based on anti PD-1/PD-L1 inhibitors has proven to be more effective than sunitinib in the first-line setting of advanced renal cell carcinoma (RCC). RCC patients with sarcomatoid histology (sRCC) have a poor prognosis and limited therapeutic options. We performed a systematic review and a meta-analysis of randomized-controlled trials (RCTs) of first-line anti PD-1/PDL-1 agents vs. sunitinib, presenting efficacy data in the sub-group of sRCC patients. The systematic research was conducted on Google Scholar, Cochrane Library, PubMed and Embase and updated until 31th January, 2020. Abstracts from ESMO and ASCO (2010–2019) were also reviewed. Full texts and abstracts reporting about RCTs testing first-line anti-PD-1/ PD-L1 agents vs. sunitinib in RCC were included if sRCC sub-group analyses of either PFS (progression-free survival), OS (overall survival) or radiological response rate were available. Pooled data from 3814 RCC patients in the ITT (intention-to-treat) population and from 512 sRCC patients were included in the quantitative synthesis. In the sRCC sub-group vs. the ITT population, pooled estimates of the PFS-HRs were 0.57 (95%: 0.45–0.74) vs. 0.79 (95% CI: 0.70–0.89), respectively, with a statistically meaningful interaction favoring the sRCC sub-group (pooled ratio of the PFS-HRs = 0.64; 95% CI: 0.50–0.82; p < 0.001). Pooled estimates of the difference in CR-R (complete response-rate) achieved with anti-PD-1/PDL-1 agents vs. sunitinib were + 0.10 (95% CI: 0.04–0.16) vs. + 0.04 (95% CI: 0.00–0.07) in the sRCC vs. the non-sRCC sub groups, with a statistically meaningful difference of + 0.06 (95% CI: 0.02–0.10; p = 0.007) favoring the sRCC sub-group. Sarcomatoid histology may be associated with improved efficacy of anti PD-1/PDL-1 agents vs. sunitinib in terms of PFS and CR-R. [ABSTRACT FROM AUTHOR]