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Background: 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 (pts). However, data regarding complications of the intense hormone therapy and surgical complications are scarce. The phase III trial PROTEUS testing ARSIs plus ADT added an amendment for thrombotic prophylaxis in the perioperative setting. We conducted a systematic review and meta-analysis to evaluate cardiovascular (CV) and thromboembolic (TE) adverse events (AEs) during neoadjuvant and perioperative intervals. Methods: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered with PROSPERO (CRD42022344104). A comprehensive search of PubMed, Embase, and Scopus databases and conference abstracts was performed from January 2010 to June 2022. Eligible studies include randomized and single-arm trials testing ARSIs prior to prostatectomy which adequately reported safety data regarding TE and CV AEs, peri-operative complications, and mortality during therapy. DerSimon and Laird method for random effects model was performed to estimate the pooled incidence (PI) of events with 95% confidence interval (95% CI). Heterogeneity was tested with I2 value. Results: 8 RCTs and 3 single-arm phase II trials comprising 674 pts were included (674 pts for CV and TE AEs and 499 for perioperative complications). Neoadjuvant regimen was classified as monotherapy with ADT (21 pts), ARSIs (100 pts), combination therapy with ADT + ARSI (338 pts), or ADT + ARSI + ARSI (215 pts). PI of all grade TE was 3.2% (95% CI, 1.6% – 4.8%, I2 = 0.0%, p = 0.92); TE incidence during perioperative period was 3.9% (95% CI, 1.6 – 6.1%, I2 = 0.0%, p = 0.67). 7 deaths were reported, with a PI of 3.0% (95% CI, 0.7–5.3%, I2 = 0.0%, p = 0.98). 2 of the mortality AE were considered treatment-related within perioperative interval. Incidence of hypertension grade 3-5 was 8.9% (95% CI, 5.2–12.7%, I2= 51.6%, p = 0.02). Incidence measures per regimen are described. Conclusions: CV and TE events associated with intense neoadjuvant hormone therapy in patients with localized PC can occur in up to 3.9% of cases. Our data warns for further assessment of thrombotic risk and prophylactic anticoagulation in this setting. Table: see text
5085
Background: Patients (pts) with high-risk localized prostate cancer (HRLPC) have a significant risk of disease recurrence and metastasis after radical prostatectomy (RP). Neoadjuvant therapy ...remains investigational but there may be a role for the next-generation androgen signaling inhibitors. We sought to evaluate pathologic and imaging response after the intense neoadjuvant approach. Methods: This is a phase II investigator-initiated randomized trial of 3-month neoadjuvant therapy with goserelin (androgen deprivation therapy, ADT) + abiraterone acetate and prednisone (AAP arm) or AAP + apalutamide (A-APA arm) before RP for pts with HRLPC (Gleason ≥ 8 and/or cT3N0-1 and/or PSA ≥ 20 ng/mL). The primary endpoint was the rate of pathologic complete response (pCR) or minimal residual disease (MRD, tumor ≤ 0.5 cm). The secondary endpoints were safety, rate of residual cancer burden ≤0.25 cm
3
(RCB = tumor volume x cellularity), Gallium 68 prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/magnetic resonance correlates and rate of biochemical relapse (BR). Results: Sixty-two pts were randomized to A-APA (N = 31) or AAP (N = 31). Median age was 65 (range 47-77) years. NCCN risk groups included high-risk disease in 19%, very high-risk in 76% and regional (N1) disease in 5% (79% cT3, 65% Gleason 8-10, 57% PSA ≥ 20 ng/mL). Outcomes after intense neoadjuvant ADT are described in the Table. There was no statistically significant difference between study arms regarding pCR/MRD or RCB ≤ 0.25 cm
3
rates. Patients with complete PSMA-PET response (psmaCR) demonstrated a RCB ≤ 0.25 cm
3
rate of 50% compared to 7.5% in pts without a psmaCR ( P= 0.001). The rate of BR was 14% for pts with RCB ≤ 0.25 cm
3
versus 38% in pts with RCB > 0.25 cm
3
( P= 0.118). At current median follow-up of 2.6 years, all patients with both psmaCR and RCB ≤ 0.25cm
3
(N = 11, 18%) are free of BR. There were 2 grade (G) 5 adverse events (AEs) in the AAP arm (pulmonary embolism and sudden death, both after surgery). Nine (14.5%) pts (6 in A-APA; 3 in AAP) experienced G3-4 treatment-related AEs. The most common G3-4 AEs were hypertension (11.3%), AST/ALT elevations (3.2%) and skin rash (1.6%). Conclusions: No difference in pCR or MRD was observed between arms. Although pCR or MRD after intense neoadjuvant ADT was infrequent, a significant proportion of pts achieved a favorable pathologic response with RCB ≤ 0.25 cm
3
. PSMA-PET response is a potential surrogate for pathologic response. Clinical trial information: NCT02789878. Table: see text
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Background: An elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with worse oncologic outcomes in several malignancies, its prognostic role in kidney cancer, ...specifically in the non metastatic setting is controversial. We aimed to evaluate if an elevated NLR in patients with locally advanced non metastatic clear cell renal cell carcinoma (CCRCC) is associated with a worse survival and/or a higher cancer recurrence rate. Methods: We retrospectively identified 880 nephrectomies performed between 01/2009 to 12/2016 in a single center, reviewed data from 478 consecutive radical nephrectomies (RN) for kidney tumors and identified 187 patients with locally advanced non-metastatic CCRCC patients (pT3-T4 N0M0). The cut-off point of NLR = 2.5 was obtained using the receiver operating curve analysis (ROC). NLR was obtained preoperatively and calculated by dividing absolute neutrophil count by absolute lymphocyte count. Overall survival (OS) and recurrence-free survival (RFS) were evaluated using the Kaplan-Meier method. Cox regression models were utilized to evaluate predictors of recurrence and survival. Results: Median follow up was 48.7 months. The 3 year OS was significantly lower for patients with NLR ≥ 2.5 than those with NLR < 2.5 (70% vs 85%, p = 0.049). In patients with a Fuhrman nuclear grade of differentiation of 3-4, the median time to recurrence was significantly shorter for patients with NLR ≥ compared to those with NLR < 4 (24 vs 55 months p 0.045). On multivariable analysis adjusted for NLR ≥ 2.5, microvascular invasion, sarcomatoid differentiation, tumor size and body mass index, only nuclear grade of differentiation was found to be an independent predictor for recurrence (hazard ratio= 2.18; 95% confidence interval CI: 1.07 – 4.92, p = 0.03). Conclusions: Patients with non-metastatic CCRCC with higher nuclear grade of differentiation and a high preoperative NLR have shorter RFS and worse OS compared to patients with lower NLR.
•Cardiovascular and thromboembolic adverse events of intense neoadjuvant hormone therapy are underreported in clinical trials.•We conducted a systematic review to evaluate the incidence of ...cardiovascular and thromboembolic events among patients with localized prostate cancer receiving neoadjuvant ARSIs prior to prostatectomy in prospective trials.•Our results corroborate the pre-clinical hypothesis of an increased risk of cardiovascular and thromboembolic adverse events associated with neoadjuvant hormone therapy following radical prostatectomy.•Relevant incidence of high-grade hypertension adverse events was observed, with significant increase in the proportion of events with the combination therapy.
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.
To evaluate the association of neutrophil-to-lymphocyte ratio (NLR) with recurrence-free survival (RFS) and overall survival (OS) in patients with locally advanced nonmetastatic clear cell renal cell ...carcinoma (ccRCC) undergoing radical nephrectomy.
We retrospectively identified 880 nephrectomies performed between January 2009 and December 2016 in a single center, reviewed data from 478 radical nephrectomies for kidney tumors and identified 187 patients with locally advanced nonmetastatic ccRCC (pT3-T4 N0M0). NLR was obtained preoperatively and calculated by dividing absolute neutrophil count by absolute lymphocyte count. OS and RFS were evaluated by the Kaplan–Meier method. Cox proportional-hazards regression models were used to evaluate predictors of RFS and OS.
Among 187 patients with ccRCC (mean age 63.4 ± 11.5 years; 118 63.1% male), the median follow-up was 48.7 months. On univariate analysis, in patients with Fuhrman nuclear grade of differentiation 3-4, the median time to recurrence was significantly shorter with NLR ≥ 4 than < 4 (24 vs. 55 months, P = .045). On multivariable analysis adjusted for NLR ≥ 4, among all variables analyzed (NLR, microvascular invasion, sarcomatoid differentiation, tumor size and body mass index), only nuclear grade of differentiation was an independent predictor of recurrence (hazard ratio 2.18; 95% confidence interval 1.07-4.92, P = .03). The 3-year OS had no statistically significant difference between patients with NLR ≥ 4 or < 4.
For patients with locally advanced, nonmetastatic ccRCC, RFS was reduced with high nuclear grade of differentiation and high preoperative NLR. These findings suggest an association between higher NLR and worse outcomes in locally advanced ccRCC.
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e16056
Background: Partial nephrectomy (PN) is the standard of care in the management of cT1a tumors, while radical nephrectomy (RN) is indicated in more advanced tumors. Recent studies ...provided evidence that PN could be performed in patients with tumors greater that 7 cm with complication rates and oncological outcomes comparable with those undergoing RN. This study compares the recurrence-free survival (RFS), overall (OS) and cancer-specific survival (CSS) of PN and RN in patients with non-metastatic pathological T3a renal cell carcinoma (RCC) with perirenal fat invasion only. Methods: We reviewed 1202 patients undergoing RN (n = 653) and PN (n = 549), at a oncological referral center, from January 2003 to June 2016. Of all patients, we identified 25 RN and 41 PN pT3a tumors with exclusively perirenal fat invasion. None had nodal or distant metastasis at pretreatment clinical staging. Patients characteristics were compared with Mann-Whitney U test and Student t-test for categorical and numeric variables with normal distribution, respectively. Both groups were compared for RFS, OS and CSS with a Kaplan-Meier survival analysis. Results: All patients included had pT3a stage with isolated perirenal fat invasion. Groups undergoing RN and PN were not significantly different regarding Charlson Comorbidity Index (Median 3 for RN vs 4 for PN, p = 0.24) or Age (Mean 65.3 for RN vs 62.0 for PN, p = 0.99). Patients undergoing RN had bigger tumors (7.9 cm vs 4.6, p < 0.001) and higher Fuhrman grade (p = 0.01). Median follow-up was 36 months for RN and 34 months for PN. At the end of follow-up, recurrence was seen in 3 patients undergoing RN (12%) and 2 undergoing PN (5%), p = 0.36. Mortality was similar across groups (16% for RN vs 15% for PN, p = 0.99) as well as Cancer-specific mortality (4% for RN vs. 5% for PN, p = 0.99). At the end of follow-up, RFS was 80% (20/25) for RN and 82% (34/41) for PN. Conclusions: In our data, renal cell carcinoma with T3 stage due to perirenal fat invasion exclusively had similar outcomes when treated with Radical or Partial Nephrectomy. OS as well as RFS were comparable for both surgical modalities, suggesting that, although RN is currently the gold standard for this staging, PN may provide similar oncologic results.
Placental polyps are defined as pedunculated or polypoid fragments of placenta or ovular membranes retained for an indefinite period of time into the uterus after abortion or child birth. An ...important cause of retention is placental accretism, an abnormal adherence of the placenta into the uterine wall. Chronic cases are rarely reported in the literature. In these cases, the placental retention in the immediate postpartum is not followed by heavy bleeding what makes the diagnosis challenging. We report a rare case of iron-deficiency anemia in a multiparous 29-year-old female patient two years after the last delivery. She sought medical care with clinical symptoms of anemia and recent menses alterations. There was no history of abortion. On gynecological examination, there was a twofold enlarged uterus, and the pelvic ultrasound revealed an image compatible with an endometrial polyp. She underwent open hysterectomy because of uncontrollable bleeding followed by hypotension after curettage. The histolopathologic examination revealed a partially hyalinized and necrotic placental polyp.
Objective: To present the partial nephrectomy series performed at our institution. Patients and Methods: 147 patients underwent nephron-sparing surgery between Jan/2000 and Feb/2011. The mean ...patient age was 60.3 yrs (33.2-82.7), and 90 (61.2%) were men. The clinical presentation, pathological tumor features, perioperative complications, functional and oncological outcomes were analyzed. Results: 84.4% of the renal masses were incidental, and the mean tumor size was 3,63 cm. Median warm ischemia time and estimated blood loss was 18 min (11-27) and 220 ml (50-480), respectively. Overall complication rate was 5%. 87.0% of the tumors were pT1, 5.7% were pT2, and 7.3% was pT3. 45 tumors were high-grade (30.6%), microvascular invasion was observed in eleven tumors (7.5%), presence of necrosis occurred in twenty-seven tumors (18.4%), and invasion of perirenal fat was identified in ten cases (6.8%). At a mean follow-up of 60 months, local recurrence was observed in only six cases (4.1%) and the cancer-specific survival in this series was 95.2%. Conclusion: Open partial nephrectomy is safe and presented optimal oncological results. It should be used for treating small renal tumors whenever is technically feasible.
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