Several phase II trials have investigated neoadjuvant novel androgen receptor signaling inhibitors (ARSIs) in combination with androgen deprivation therapy (ADT) followed by radical prostatectomy (RP) in prostate cancer (PC) patients. However, data regarding complications of intense hormone therapy and surgical complications are scarce. Our objective was to evaluate the occurrence of cardiovascular (CV) and thromboembolic (TE) adverse events (AE) in patients with localized PC who have received intense neoadjuvant ADT followed by prostatectomy. A comprehensive search in MEDLINE, Embase, Scopus and conference abstracts was performed. The strategies were developed and applied for each electronic database on March 7th, 2023. Eligible studies included randomized and single-arm trials testing ARSIs prior to prostatectomy that adequately reported safety data regarding CV and TE AE, peri-operative complications, and mortality during therapy. Pooled incidence (PI) of AE with 95% confidence interval (95% CI) was estimated using a random effects model. Quality assessment and reporting followed Cochrane Collaboration Handbook and PRISMA guidelines. PROSPERO: CRD42022344104. Nine randomized controlled trials and three single-arm phase II trials were included, comprising 702 patients (702 patients for CV AE and 522 for perioperative complications). The neoadjuvant regimen was classified as monotherapy with ARSI (100 patients), combination therapy with ADT + ARSI (383 patients), or ADT + ARSI + ARSI (219 patients). The PI of TE within the perioperative interval was 4.2% (95% CI = 2.6%-6.6%, I2 = 0.0%, P = .65), and the PI for CV AE was 4.6% (95% CI = 3.1%-6.7%, I2 = 0.0%, P = .71). Seven deaths were reported, resulting in a PI of 2.2% (95% CI = 1.3%-3.8%, I2 = 0.0%, P = .99), of which two were considered treatment-related and occurred within the perioperative period. The PI of hypertension grade 3-5 was 7.3% (95% CI = 4.8%-11.0%, I2 = 38.8%, P = .04). CV and TE AE associated with intense neoadjuvant hormone therapy in patients with localized PC can occur in up to 4.6% of cases. Our data warns for further assessment of thrombotic risk and prophylactic anticoagulation in this setting.

BACKGROUND: Patients with localized, unfavorable intermediate-risk and high-risk prostate cancer have an increased risk of relapse after radical prostatectomy (RP). The authors previously reported on part 1 of this phase 2 trial testing neoadjuvant apalutamide, abiraterone, prednisone, plus leuprolide (AAPL) or abiraterone, prednisone, and leuprolide (APL) for 6 months followed by RP. The results demonstrated favorable pathologic responses (tumor <5 mm) in 20.3% of patients (n = 24 of 118). Herein, the authors report the results of part 2.
METHODS: For part 2, patients were randomized 1:1 to receive either AAPL for 12 months (arm 2A) or observation (arm 2B), stratified by neoadjuvant therapy and pathologic tumor classification. The primary end point was 3-year biochemical progression-free survival. Secondary end points included safety and testosterone recovery (>200 ng/dL).
RESULTS: Overall, 82 of 118 patients (69%) enrolled in part 1 were randomized to part 2. A higher proportion of patients who were not randomized to adjuvant therapy had a favorable prostatectomy pathologic response (32.3% in nonrandomized patients compared with 17.1% in randomized patients). In the intent-to-treat analysis, the 3-year biochemical progression-free survival rate was 81% for arm 2A and 72% for arm 2B (hazard ratio, 0.81; 90% confidence interval, 0.43-1.49). Of the randomized patients, 81% had testosterone recovery in the AAPL group compared with 95% in the observation group, with a median time to recovery of <12 months in both arms.
CONCLUSIONS: In this study, because 30% of patients declined adjuvant treatment, part B was underpowered to detect differences between arms. Future perioperative studies should be biomarker-directed and include strategies for investigator and patient engagement to ensure compliance with protocol procedures.

BACKGROUND: The most prevalent subtype of breast cancer (BC) is luminal hormonal-positive breast cancer. The neoadjuvant chemotherapy regimens have side effects, emphasizing the need to identify new startegies.
OBJECTIVE: Analyze the complete pathologic response (pCR) rate and overall response in a low-risk hormone-positive subset of patients receiving neoadjuvant hormone treatment (NAHT) with or without Palbociclib (a CDK4/CDK6 inhibitor) to boost NAHT effectiveness.
METHODS: Based on the upfront 21-gene Oncotype DX or low-risk Breast Recurrence Score assay (RS™), the SAFIA trial is designed as a prospective multicenter international, double-blind neoadjuvant phase-III trial that selects operable with luminal BC patients that are HER2-negative for the induction hormonal therapy with Fulvestrant 500 mg ± Goserelin (F/G) followed by randomization of responding patients to palbociclib versus placebo. The pCR rate served as the study\'s main outcome, while the secondary endpoint was a clinical benefit.
RESULTS: Of the 354 patients enrolled, 253 initially responded and were randomized to either F/G fulvestrant with palbociclib or placebo. Two hundred twenty-nine were eligible for the evaluation of the pathologic response. No statistically significant changes were observed in the pCR rates for the patients treated with the F/G therapy with placebo or palbociclib (7% versus 2%, respectively) per the Chevallier classification (Class1 + Class2) (p = 0.1464) and 3% versus 10% assessed per Sataloff Classification (TA, NA/NB) (p = 0.3108). Palbociclib did not increase the rate of complete pathological response.
CONCLUSIONS: Neoadjuvant hormonal therapy is feasible in a selected population with a low RS score of < 31 CLINICAL TRIAL: NCT03447132.

To analyze the perioperative outcomes of neoadjuvant hormone therapy (NHT) before laparoscopic and robot-assisted surgery for localized high-risk prostate cancer in a Chinese cohort.
The clinical data of 385 patients with localized high-risk prostate cancer who underwent radical prostatectomy (RP) in our hospital from January 2019 to June 2021 were analyzed retrospectively, including 168 patients with preoperative NHT and 217 patients with simple surgery. Clinical characteristics were compared in the above two groups, the laparoscopic RP (LRP) cohort (n = 234) and the robot-assisted laparoscopic radical prostatectomy (RALP) cohort (n = 151), respectively.
In the overall cohort, compared with the control group, the NHT group had a shorter operative time, less blood loss, a lower positive surgical margin rate, and a higher proportion of Gleason score (GS) downgrading after the operation (p < 0.05). However, there was no significant difference in hospitalization time, biochemical recurrence, urine leakage, urinary continence, or prostate-specific antigen (PSA) progression-free survival (p > 0.05). In the LRP cohort, it was found that the NHT group also had shorter operative time, less blood loss, lower positive surgical margin rate, a higher proportion of GS downgrading after the operation, and faster recovery of urinary control than the control group (p < 0.05). There was no marked difference in hospitalization time, biochemical recurrence, urinary leakage, or PSA progression-free survival. However, in the RALP cohort, the NHT group had a significant difference in the GS downgrading after the operation compared with the control group (p < 0.05). In the overall cohort, multiple analyses showed that initial PSA level, GS at biopsy, clinical T stage, lymph node invasion, use of NHT, and surgical methods were significantly associated with positive surgical margin (p < 0.05) while NHT did not account for biochemical recurrence (p > 0.05).
NHT can lower the difficulty of surgery, reduce positive surgical margin rate, and help recovery in short-term urinary control in patients with high-risk prostate cancer after LRP. However, we do not have evidence on the benefit of NHT in high-risk PCa patients treated with RALP. For these patients, surgery can be performed as early as possible.

UNASSIGNED: Despite neoadjuvant hormone therapy (NHT) is being underused, it is an effective treatment for luminal tumors at a lower cost and with fewer side effects compared to those associated with neoadjuvant chemotherapy (NCT). The lack of robust comparative data between NHT and NCT is a factor that limits its use in clinical practice.
UNASSIGNED: This study will be a randomized, open-label, non-inferiority clinical trial. Patients diagnosed with HER2-negative luminal-subtype breast cancer will be identified at the time of diagnosis. Menopausal patients randomized for NHT should receive anastrozole for at least six months. Premenopausal women should receive anastrozole associated with subcutaneous goserelin acetate every 12 weeks for at least six months. Patients randomized for NCT will receive a standard institutional regimen based on anthracyclines and taxanes. Sample size was calculated considering the CPS + EG as a method for evaluating response and prognosis, where a score <3 was defined as good. The non-inferiority margin for NHT was set at 15%. The study considered a power of 80%, a significance level of 5%, and an outcome proportion in each group of 69%, resulting in 118 patients in each group. We estimated at 10% of losses, resulting in a sample of 130 patients in each group.
UNASSIGNED: The non-inferiority of NHT in relation to NCT will provide further evidence that replacing NCT with NHT is safe and effective in eligible patients, which is particularly relevant for populations with limited access to health services and for institutions with few available resources.

UNASSIGNED: This systematic study aimed to assess and compare the comprehensive evidence regarding the impact of neoadjuvant hormone therapy (NHT) on surgical and oncological outcomes of patients with prostate cancer (PCa) before radical prostatectomy (RP).
UNASSIGNED: Literature searches were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Using PubMed, Web of Science, Chinese National Knowledge Infrastructure, and Wanfang databases, we identified relevant studies published before July 2020. The pooled effect sizes were calculated in terms of the odds ratios (ORs)/standard mean differences (SMDs) with 95% confidence intervals (CIs) using the fixed or random-effects model.
UNASSIGNED: We identified 22 clinical trials (6 randomized and 16 cohort) including 20,199 patients with PCa. Our meta-analysis showed no significant differences in body mass index (SMD = 0.10, 95% CI: -0.08-0.29, p = 0.274) and biopsy Gleason score (GS) (OR = 1.33, 95% CI: 0.76-2.35 p = 0.321) between the two groups. However, the NHT group had a higher mean age (SMD = 0.19, 95% CI: 0.07-0.31, p = 0.001), preoperative prostate-specific antigen (OR = 0.47, 95% CI: 0.19-0.75, p = 0.001), and clinic tumor stage (OR = 2.24, 95% CI: 1.53-3.29, p < 0.001). Compared to the RP group, the NHT group had lower positive surgical margins (PSMs) rate (OR = 0.44, 95% CI: 0.29-0.67, p < 0.001) and biochemical recurrence (BCR) rate (OR = 0.47, 95% CI: 0.26-0.83, p = 0.009). Between both groups, there were no significant differences in estimated blood loss (SMD = -0.06, 95% CI: -0.24-0.13, p = 0.556), operation time (SMD = 0.20, 95% CI: -0.12-0.51, p = 0.219), pathological tumor stage (OR = 0.76, 95% CI: 0.54-1.06, p = 0.104), specimen GS (OR = 0.91, 95% CI: 0.49-1.68, p = 0.756), and lymph node involvement (OR = 0.76, 95% CI: 0.40-1.45, p = 0.404).
UNASSIGNED: NHT prior to RP appeared to reduce the tumor stage, PSMs rate, and risk of BCR in patients with PCa. According to our data, NHT may be more suitable for older patients with higher tumor stage. Besides, NHT may not increase the surgical difficulty of RP.

This study aimed to identify the pathological outcomes and survival benefits of neoadjuvant hormone therapy (NHT) combined with radical prostatectomy (RP) and radiotherapy (RT) administered to patients with high-risk prostate cancer (HRPCa). We searched PubMed, Embase, and the Cochrane Library for studies comparing NHT plus RP or RT with RP or RT alone, administered to patients with HRPCa. We used a random-effects model to compute risk estimates with 95% confidence intervals (CIs) and quantified heterogeneity using the I \"2\" statistic. Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity. We selected 16 studies. NHT before RP significantly decreased lymph node involvement (risk ratio [RR] = 0.69, 95% CI: 0.56-0.87) and increased the rates of pathological downstaging (RR = 2.62, 95% CI: 1.22-5.61) and organ-confinement (RR = 2.24, 95% CI: 1.54-3.25), but did not improve overall survival and biochemical progression-free survival (bPFS). The administration of NHT before RT to patients with HRPCa was associated with significant benefits for cancer-specific survival (hazard ratio [HR] = 0.51, 95% CI: 0.39-0.68), disease-free survival (HR = 0.51, 95% CI: 0.44-0.60), and bPFS (HR = 0.54, 95% CI: 0.46-0.64). Short-term NHT combined with RT administered to patients with HRPCa conferred significant improvements. Although the advantage of local control was observed when NHT was administered before RP, there was no significant survival benefit associated with HRPCa. Therefore, short-term NHT combined with RT is recommended for implementation in standard clinical practice but not for patients who undergo RP.

UNASSIGNED: Breast cancer management during COVID-19 pandemic has changed and in case of COVID-19 patients with simultaneous neoplasia, it has been strongly recommended to treat Sars-CoV-2 infection firstly.
UNASSIGNED: We reported a case of a 53-years-old women with early breast cancer and simultaneous asymptomatic SARS-CoV-2 infection. According to COVID-19 breast cancer recommendations she underwent hormone neoadjuvant treatment as a bridging therapy for surgery. Six months from the diagnosis, after virus eradication, patient underwent breast surgery. No SARS-CoV-2 RNA was found both in the surgical specimen and sentinel lymph node but micrometastasis were reported. During the last follow-up, the patient was in good clinical condition and started the adjuvant chemotherapy.
UNASSIGNED: COVID-19 outbreak determined the publication of temporary recommendation leading to an extensive use of neoadjuvant chemotherapy in breast cancer patients. Although endocrine therapy is a mainstay in the adjuvant treatment, its role in the neoadjuvant schedule is unclear.
UNASSIGNED: Upfront awake surgery should be preferred especially in asymptomatic COVID-19 patient with early breast cancer when monitoring of tumor response is not feasible.

UNASSIGNED: The logic behind the outcome of endocrine therapy in breast cancer has long remained poorly understood. The prognostic role of DNA damage and repair biomarkers (DDR) was explored in postmenopausal, hormone-receptor-positive breast cancer patients treated with neoadjuvant hormone therapy (NAHT).
UNASSIGNED: Data on 55 patients were included. The phosphorylated ataxia-teleangectasia and Rad3-related protein (pATR), phosphorylated ataxia-telangiectasia mutated (ATM) kinase, and phosphorylated H2A Histone Family Member X (γ-H2AX) were evaluated by immunohistochemistry in paired tissues collected at baseline and following NAHT. Biomarkers were considered both singularly and within signatures. Ki-67 percentage change was the primary biomarker endpoint. Classical endpoints were also considered.
UNASSIGNED: The most favorable Ki-67 outcome was associated with the γ-H2AX/pATM signature (p = 0.011). In models of Ki-67 reduction, \'luminal B\' subtype, higher grade of anaplasia, and the γ-H2AX/pATM signature tested as significant (p < 0.05 for all). Results were confirmed in multivariate analysis. No association was observed with pathologic response. An increase of ∆γ-H2AX in paired breast tissues was associated with longer event-free survival (p = 0.027) and overall survival (p = 0.042). In Cox models, both survival outcomes were solely affected by grade of anaplasia, with less favorable prognosis in the highest grades (p < 0.05 for both).
UNASSIGNED: We report novel evidence of the prognostic role of DDR biomarkers on important patient outcomes in postmenopausal hormone-receptor-positive breast cancer patients treated with NAHT. If confirmed in future and adequately sized trials, our results may help inform therapeutic decisions and clarify underlying biological mechanisms.

Purpose: Radical surgery is the preferred method for local high-risk and limited progressive prostate cancer in the routine clinical setting. However, current guidelines do not recommend neoadjuvant hormone therapy (NHT). Opinions regarding NHT vary among individual clinicians. According to the experience gained at our center, we explored the benefits of NHT for patients with prostate cancer during the perioperative period in this study. Methods: In this retrospective study, we explored the perioperative benefits of NHT among 189 patients with local high-risk or limited progressive prostate cancer who underwent radical prostatectomy and divided them into two groups: the NHT group and the non-NHT group. The NHT regimens were a gonadotropin-releasing hormone (GnRH) agonist alone (3.75/11.25 mg of leuprolide or 3.6/10.8 mg of goserelin acetate), an androgen receptor antagonist (ARA) alone, or a combination of the two. The duration of treatment was <3 months, 3 to 6 months, or >6 months. Results: We found that NHT could reduce the surgery time and intraoperative hemorrhage, thus reducing the difficulty of surgery; NHT could also improve the postoperative recovery of patients. However, it did not reduce the stage of prostate cancer or positive surgical margin rate. Conclusions: Neoadjuvant therapy is optional for some patients. We believe that NHT will improve the overall prognosis of patients as progress continues in the medical field in the future.