Objective
To evaluate the efficacy and safety of apalutamide prostate cancer compared to the pivotal trials patients and to identify the first subsequent therapy in a real‐world setting.
Methods
The ...study is prospective and observational based on real‐world evidence, performed by different medical disciplines and eight academics centres around Barcelona, Spain. It included all patients with metastatic hormone‐sensitive prostate cancer (mHSPC) and high‐risk non‐metastatic castration‐resistant prostate cancer (nmCRPC) treated with apalutamide from June 2018 to December 2022.
Results
Of 227 patients treated with apalutamide, 10% had ECOG‐PS 2, and 41% were diagnosed with new‐generation imaging. In the mHSPC group (209 patients), 75 years was the median age, 53% had synchronous metastases, and 22% were M1a. In the nmCRPC (18 patients), 82 years was the median age, and 81% ≤6 months had PSA doubling time. Patients achieved PSA90 in 92% of mHSPC and 50% of nmCRPC and PSA ≤0.2 in 71% of mHSPC and 39% of nmCRPC. Treatment‐related adverse events occurred in 40.1% of mHSPC and 44.4% of nmCRPC. After discontinuation of apalutamide due to disease progression, 54.5% in mHSPC and 75% in nmCRPC started chemotherapy, while after discontinuation because of adverse events, 73.3% in mHSPC and 100% in nmCRPC continued with other hormonal‐therapies.
Conclusions
The efficacy and safety of apalutamide were similar to that described in the pivotal trials, despite including an older and more comorbid population. Usually, subsequent therapies after apalutamide differed depending on the reason for discontinuation: by disease progression started chemotherapy and by adverse events hormonal sequencing.
This study is prospective and observational based on real‐world evidence, performed by different medical disciplines and eight academic centres around Barcelona, Spain. It included all patients with metastatic hormone‐sensitive prostate cancer (mHSPC) and high‐risk non‐metastatic castration‐resistant prostate cancer (nmCRPC) treated with apalutamide. Of 227 patients treated with apalutamide, 10% had ECOG‐PS 2, and 41% were diagnosed with new‐generation imaging. In the mHSPC group (209 patients), 75 years was the median age, 53% had synchronous metastases, and 22% were M1a. In the nmCRPC (18 patients), 82 years was the median age, and 81% of ≤6 months had PSA doubling time. Patients achieved PSA90 in 92% of mHSPC and 50% of nmCRPC and PSA ≤0.2 in 71% of mHSPC and 39% of nmCRPC. In conclusion, the efficacy and safety of apalutamide were similar to that described in the pivotal trials, despite including an older and more comorbid population. Usually, subsequent therapies after apalutamide differed depending on the reason for discontinuation: by disease progression started chemotherapy and by adverse events hormonal sequencing.
OBJECTIVE
To describe the chromosomal numerical changes present in primary prostate tumours and their matched lymph‐node metastases, to identify a clonal cell migration process which could account ...for the metastatic behaviour.
MATERIALS AND METHODS
Twenty‐eight cases of unsuspected stage D1 (pT2–3pN1M0) prostate cancer were detected among patients who had a radical prostatectomy for clinically localized prostate cancer. Fluorescence in situ hybridization (FISH), using centromeric probes to enumerate chromosomes 7, 8, 10 and 12, was used to assess numerical chromosomal changes. FISH analysis was used on isolated nuclei obtained from matched primary tumours and their lymph node metastases.
RESULTS
Of the 28 suitable cases it was possible to complete the study in 18 pairs of matched tissues; the remainder were excluded because of insufficient tissue or poor preservation of at least one of the tissues. There was cytogenetic change (aneuploidy) in 16 of the 18 primary tumours, the most common being monosomy 8, detected in 14, followed by trisomy 7, in 13 aneuploid tumours. All lymph node metastases were aneuploid by FISH. As in the primary tumours, monosomy 8 and trisomy 7 were the most common cytogenetic alterations, in 13 and 15 of the lymph node tissues. FISH analysis showed a high correlation (83%) in the cytogenetic pattern of changes between the primary tumours and their lymph node metastases. Moreover, a similar number of cells had the most common aneusomies when comparing prostate and the lymph node tissues.
CONCLUSIONS
These results show a similar pattern of cytogenetic alteration in the primary tumour and its lymph node metastasis, characterized by the frequent presence of trisomy 7 and monosomy 8, suggesting that clonal cell selection is not involved in the metastatic process.
Abstract Context New data regarding diagnosis and treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) ...guidelines for MiM-BC. Objective To review the new EAU guidelines for MiM-BC. Evidence acquisition A comprehensive workup of the literature obtained from Medline, the Cochrane central register of systematic reviews, and reference lists in publications and review articles was developed and screened by a group of urologists, oncologists, and radiologist appointed by the EAU Guideline Committee. Previous recommendations based on the older literature on this subject were taken into account. Levels of evidence and grade of guideline recommendations were added, modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. Evidence synthesis The diagnosis of muscle-invasive bladder cancer (BCa) is made by transurethral resection (TUR) and following histopathologic evaluation. Patients with confirmed muscle-invasive BCa should be staged by computed tomography (CT) scans of the chest, abdomen, and pelvis, if available. Adjuvant chemotherapy is currently only advised within clinical trials. Radical cystectomy (RC) is the treatment of choice for both sexes, and lymph node dissection should be an integral part of cystectomy. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for clinical or personal reasons. An appropriate schedule for disease monitoring should be based on (1) natural timing of recurrence, (2) probability of disease recurrence, (3) functional deterioration at particular sites, and (4) consideration of treatment of a recurrence. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin is cisplatin-containing combination chemotherapy. Presently, there is no standard second-line chemotherapy. Conclusions These EAU guidelines are a short, comprehensive overview of the updated guidelines of (MiM-BC) as recently published in the EAU guidelines and also available in the National Guideline Clearinghouse.
NOTES (Natural Orifice Transluminal Endoscopic Surgery) is a surgical modality that uses empty organs as an access to the peritoneal cavity, avoiding skin incisions. If we combine this surgery with ...the classical laparoscopic approach, a new hybrid technique is obtained. This approach will permit us to work on wide operating fields with large organs, as the kidney, minimizing skin incisions. We present the first hybrid transvaginal radical nephrectomy due to renal cancer. In order to perform this procedure, we used a vaginal access for introduction of a deflectable camera and the assistance of two additional abdominal trocars. The vaginal incision for the trocar was enlarged for organ removal. Hybrid transvaginally NOTES assisted radical nephrectomy is a reproducible and feasible technique that has to be kept in mind for women who are candidates to nephrectomy for renal cancer.
We assessed mutations in ERCC2, ERBB2, and ATM/RB1/FANCC as predictors of pathological response to neoadjuvant chemotherapy in bladder cancer. We confirmed an association of ERCC2 mutations with ...pathological response, but not with complete response, overall survival, or recurrence-free survival. Alterations in ERBB2 or ATM/RB1/FANCC were not predictive.
Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy is recommended for patients with muscle-invasive bladder cancer (MIBC). It has been shown that somatic deleterious mutations in ERCC2, gain-of-function mutations in ERBB2, and alterations in ATM, RB1, and FANCC are correlated with pathological response to NAC in MIBC. The objective of this study was to validate these genomic biomarkers in pretreatment transurethral resection material from an independent retrospective cohort of 165 patients with MIBC who subsequently underwent NAC and radical surgery. Patients with ypT0/Tis/Ta/T1N0 disease after surgery were defined as responders. Somatic deleterious mutations in ERCC2 were found in nine of 68 (13%) evaluable responders and two of 95 (2%) evaluable nonresponders (p = 0.009; FDR = 0.03). No correlation was observed between response and alterations in ERBB2 or in ATM, RB1, or FANCC alone or in combination. In an exploratory analysis, no additional genomic alterations discriminated between responders and nonresponders to NAC. No further associations were identified between the aforementioned biomarkers and pathological complete response (ypT0N0) after surgery. In conclusion, we observed a positive association between deleterious mutations in ERCC2 and pathological response to NAC, but not overall survival or recurrence-free survival. Other previously reported genomic biomarkers were not validated.
It is currently unknown which patients will respond to chemotherapy before definitive surgery for bladder cancer. Previous studies described several gene mutations in bladder cancer that correlated with chemotherapy response. This study confirmed that patients with bladder cancer with a mutation in the ERCC2 gene often respond to chemotherapy.
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