Neoadjuvant Chemohormonal Therapy in Prostate Cancer Before Radical Prostatectomy: A Systematic Review and Meta-Analysis

Abstract

ObjectiveThis meta-analysis was to investigate the effects of neoadjuvant chemohormonal therapy (NCHT) on patients with prostate cancer (PCa) before radical prostatectomy (RP) and attempt to provide meaningful evidence.MethodsA systematic search was performed using the PubMed, Web of Science, and Cochrane Library databases in February 2022 based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The relevant studies were critically screened and we extracted the data of demography, postoperative pathology, and survival to calculate the pooled effect sizes. Subgroup analyses and sensitivity analyses were used to explore the source of heterogeneity.ResultsSix identified studies involving 1717 subjects were included according to the selection criteria. There was no significant difference between NCHT plus RP and RP alone groups regarding lymph node involvement (risk ratio [RR]=1.03, 95% confidence interval [CI]: 0.57-1.87, P=0.92). However, NCHT prior to RP significantly decreased the rates of positive surgical margin (PSM, RR=0.35, 95% CI: 0.22-0.55, P<0.0001) and seminal vesicle invasion (SVI, RR=0.78, 95% CI: 0.65-0.95, P=0.01), and increase pathological downstaging (RR=1.64, 95% CI: 1.17-2.29, P=0.004). Additionally, biochemical recurrence-free survival (BRFS) and overall survival (OS) were significantly prolonged under the administration of NCHT (HR=0.54, 95% CI: 0.34-0.85, P=0.008 and HR=0.67, 95% CI: 0.48-0.94, P=0.02, respectively).ConclusionsCompared to the RP alone group, patients with NCHT plus RP showed significant improvements in PSM, SVI, pathological downstaging, BRFS, and OS, whereas further multicenter randomized controlled trials are needed to consolidate this concept.

Efficacy and Safety of Neoadjuvant Luteinizing Hormone-Releasing Hormone Antagonist and Tegafur-Uracil Chemohormonal Therapy for High-Risk Prostate Cancer

“…Although several guidelines recommend that surgery be part of a comprehensive treatment for high-risk PCa [ 2 , 4 ], pathological findings suggest that a relatively high proportion of PSM may not be cured by RP and consequently require adjuvant therapy [ 38 ]. Therefore, neoadjuvant therapy is administered to improve surgical and oncologic outcomes in patients with high-risk PCa [ 15 , 16 , 40 , 41 , 42 ]. NHT prior to RP has been tried in combination with cytotoxic agents as it was found to increase the negative surgical margin rate but not prevent BCR [ 15 , 16 , 17 , 18 , 19 , 20 ].…”

“…Recently, Ravi et al [ 42 ] reported the efficacy of NHT with second-generation antiandrogens before RP in high-risk patients with PCa. After inverse probability of treatment weighting, time to BCR (HR = 0.25) and metastasis-free survival (HR = 0.26) were significantly longer in patients receiving NHT with second-generation antiandrogens than in those receiving RP alone [ 41 ]. In our previous studies, neoadjuvant LHRH plus EMP followed by RP was significantly associated with oncological outcomes, such as BRFS and OS, compared to RP alone for high-risk PCa [ 18 , 19 , 20 ].…”

Treatment Strategies for High-Risk Prostate Cancer - Utility of Combination Therapy of Neoadjuvant Therapy and Radical Prostatectomy to Improve Oncologic Outcomes

“…Therefore, we currently perform NCHT with GnRH and tegafur-uracil (UFT) for highrisk PCa [55]. Multiple studies have reported the efficacy and safety of UFT-containing regimens for a variety of malignant neoplasms, including lung cancer, breast cancer, gastric cancer, and castrationresistant PCa (CRPC) [56][57][58][59]. For CRPC in particular, the usefulness of UFTs has been demonstrated when administered late-line or in combination with other anticancer agents [56][57][58][59].…”

Androgen deprivation therapy plus apalutamide as neoadjuvant therapy prior radical prostatectomy for patients with unresectable prostate cancer

“…The main goals of neoadjuvant therapy for prostate cancer (PCa) based on androgen deprivation therapy (ADT) are to reduce tumor size, reduce the rate of positive surgical margins, and achieve pathological remission, but no benefit has been observed in terms of cancer-related death ( Ge et al, 2022 ; Wang et al, 2022 ). Thus, neoadjuvant therapy has not been recommended as the primary treatment option for patients with progressive PCa ( Ge et al, 2022 ; Wang et al, 2022 ).…”

“…The main goals of neoadjuvant therapy for prostate cancer (PCa) based on androgen deprivation therapy (ADT) are to reduce tumor size, reduce the rate of positive surgical margins, and achieve pathological remission, but no benefit has been observed in terms of cancer-related death ( Ge et al, 2022 ; Wang et al, 2022 ). Thus, neoadjuvant therapy has not been recommended as the primary treatment option for patients with progressive PCa ( Ge et al, 2022 ; Wang et al, 2022 ). In the past 20 years, the emergence of new-generation androgen receptor signaling inhibitors (ARSI), such as abiraterone, apalutamide, enzalutamide, and darolutamide, has increased interest in the neoadjuvant treatment of PCa ( Devos et al, 2021 ).…”