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1.

Background

Prostate-specific membrane antigen (PSMA)–targeted positron emission tomography (PET) can visualize metastatic lesions in recurrent prostate cancer (PC). However, reliable identification of small and/or atypically localized lesions during salvage surgery procedures is challenging.

Objective

To describe the technique, feasibility, and short-term outcomes of 99mTechnetium (99mTc)-based PSMA-radioguided surgery (99mTc-PSMA-RGS) for removal of recurrent PC lesions.

Design, setting, and participants

Thirty-one consecutive patients with evidence of recurrent PC on 68Ga-PSMA N,N′-bis[2-hydroxy-5-(carboxyethyl)benzyl] ethylenediamine-N,N′-diacetic acid (68Ga-PSMA-11) PET after radical prostatectomy undergoing 99mTc-PSMA-RGS were retrospectively analyzed.

Surgical procedure

Salvage surgery with intraoperative radioguidance using a gamma probe was performed after intravenous application of 99mTc-PSMA investigation and surgery (mean activity 571 MBq, mean time to surgery 19.7 h).

Measurements

Radioactive rating (positive vs negative) of resected tissue was compared with the findings of postoperative histopathological analysis. Best prostate-specific antigen (PSA) response without additional treatment was determined after 8–16 wk postoperatively. Biochemical recurrence- and treatment-free survival was evaluated.

Results and limitations

In total, 132 tissue specimens were removed, of which 58 showed metastatic involvement on histological analysis. On a specimen basis, radioactive rating yielded a sensitivity of 83.6% (confidence interval [CI]: 70.9–91.5%), a specificity of 100%, and an accuracy of 93.0% (CI: 85.5–96.7%). With 99mTc-PSMA-RGS, all lesions visualized on preoperative 68Ga-PSMA-11 PET could be removed. Moreover, 99mTc-PSMA-RGS detected additional metastases as small as 3 mm in two patients. Thirteen patients suffered from complications related to surgery (Clavien-Dindo grade 1: 12 patients; grade 3a: one patient). A PSA reduction below 0.2 ng/ml was observed in 20 patients. Thirteen patients remained biochemical recurrence free after a median follow-up of 13.8 (range: 4.6–18.3) mo. Twenty patients continued to be treatment free after a median follow-up of 12.2 (range: 5.5–18.3) mo.

Conclusions

As a new technique for surgical guidance, 99mTc-PSMA-RGS is feasible, and has been proved to be of high value for successful intraoperative detection and removal of metastatic lesions in PC patients scheduled for salvage surgery. Its long-term impact on outcome has to be evaluated.

Patient summary

In this report, we evaluated a novel technique to identify metastatic lesions intraoperatively in patients with recurrent prostate cancer to facilitate surgical removal. After intravenous injection of radioactive molecules that specifically bind to prostate cancer cells that show increased expression of the prostate-specific membrane antigen, we were able to detect and remove these metastatic lesions during surgery. Following salvage surgery, 41.9% of patients remained biochemical recurrence free (median follow-up of 13.8 mo) and 64.5% continued to be treatment free (median follow-up of 12.2 mo).  相似文献   

2.
Background 18F-Fluorodeoxyglucose (FDG)-positron emission tomography (PET) and computed tomography (CT) are widely accepted in the evaluation for metastatic or recurrent rectal cancer. Only spiral CT and transrectal ultrasonography (TRUS) are routinely used in the initial evaluation of primary rectal cancer. We wished to determine whether PET/CT could provide additional information in patients undergoing standard evaluation for primary rectal cancer. Methods Thirty-seven patients (mean age, 58 years; range, 26–90 years) with a previously untreated rectal cancer underwent TRUS or magnetic resonance imaging, spiral CT, and FDG-PET/CT. The tumor location (low, ≤6 cm; mid, 7–10 cm; or high, ≥10 cm) and carcinoembryonic antigen level were recorded. Discordant findings between spiral CT and FDG-PET/CT were confirmed by histological analysis or imaging follow-up. Results FDG-PET/CT identified discordant findings in 14 patients (38%), and this resulted in upstaging of 7 patients (50%) and downstaging of 3 patients (21%). Although node-positive disease on TRUS/magnetic resonance imaging was associated with discordant FDG-PET/CT findings, this was not statistically significant. Discordant PET/CT findings were significantly more common in patients with a low rectal cancer than in those with mid or high rectal cancer (13 vs. 1; P = .0027). The most common discordant finding was lymph node metastasis (n = 7; 50%). Histological confirmation of discordant FDG-PET/CT findings was performed in seven patients, and in no case did FDG-PET/CT prove to be inaccurate. Discordant PET/CT findings resulted in a deviation in the proposed treatment plan in 27% of patients (n = 10). Conclusions FDG-PET/CT frequently yields additional staging information in patients with low rectal cancer. Improved accuracy of pretreatment imaging with FDG-PET/CT will allow for more appropriate stage-specific therapy. Presented at the Annual Meeting of the Society of Surgical Oncology, Atlanta, Georgia, March 3–6, 2005.  相似文献   

3.
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5.
Background: Exact preoperative staging of esophageal cancer is essential for accurate prognosis and selection of appropriate treatment modalities.Methods: Forty-two patients with adenocarcinoma of the esophagus or the esophagogastric junction suitable for radical esophageal resection were staged with positron emission tomography (PET), spiral computed tomography (CT), and endoscopic ultrasonography (EUS).Results: Diagnostic sensitivity for the primary tumor was 83% for PET and 67% for CT; for local peritumoral lymph node metastasis, it was 37% for PET and 89% for EUS; and for distant metastasis, it was 47% for PET and 33% for CT. Diagnostic specificity for local lymph node metastasis was 100% with PET and 54% with EUS, and for distant metastasis, it was 89% for PET and 96% for CT. Accuracy for locoregional lymph node metastasis was 63% for PET, 66% for CT, and 75% for EUS, and for distant metastasis, it was 74% with PET and 74% with CT. Of the 10 patients who were considered inoperable during surgery, PET identified 7 and CT 4. The false-negative diagnoses of stage IV disease in PET were peritoneal carcinomatosis in two patients, abdominal para-aortic cancer growth in one, metastatic lymph nodes by the celiac artery in four, and metastases in the pancreas in one. PET showed false-positive lymph nodes at the jugulum in three patients.Conclusions: The diagnostic value of PET in the staging of adenocarcinoma of the esophagus and the esophagogastric junction is limited because of low accuracy in staging of paratumoral and distant lymph nodes. PET does, however, seem to detect organ metastases better than CT.  相似文献   

6.

Context

Choline positron emission tomography (PET)/computed tomography (CT) is a currently used diagnostic tool in restaging prostate cancer (PCa) patients with increasing prostate-specific antigen (PSA) after either radical prostatectomy (RP) or external-beam radiation therapy (EBRT). However, no final recommendations have been made on the use of this modality for patient management.

Objective

To critically analyse the current evidence for the use of choline PET/CT scanning in the management of patients with a progressive increase in PSA after radical treatment for PCa, evaluating its diagnostic accuracy in the detection of recurrences, the clinical predictors of positive PET/CT examinations, and the modalities’ role as a guide for tailored therapeutic strategies.

Evidence acquisition

Data on recently published (2003–2010) original articles, review articles, and editorials concerning the role of choline PET/CT in this scenario were analysed.

Evidence synthesis

The diagnostic accuracy of choline PET in detecting sites of PCa relapse has been investigated by several authors, and the overall reported sensitivity ranges between 38% and 98%. It has been demonstrated that choline PET technology's positive detection rate improves with increasing PSA values. The routine use of choline PET/CT cannot be recommended for PSA values <1 ng/ml. However, in addition to PSA serum value, PSA doubling time (PSA DT), and other clinical and pathologic features—including locally advanced tumour (pT3b–T4) or lymph node involvement at initial staging—should be considered to refer patients to choline PET/CT study. Choline PET/CT may be also proposed as a image guide either for experimental surgical or radiation therapy treatments.

Conclusions

According to the current available data, choline PET/CT plays a role in the management of biochemical relapse. Its accuracy is correlated to PSA value, PSA DT, and other pathologic features. Choline PET/CT may be proposed as a guide for individualised treatment of recurrence.  相似文献   

7.
8.

Context

Determination of tumour involvement of regional lymph nodes in patients with prostate cancer (PCa) is of key importance for the proper planning of treatment.

Objectives

To provide a critical overview of published reports and to perform a meta-analysis about the diagnostic performance of 18F-choline and 11C-choline positron emission tomography (PET) or PET/computed tomography (CT) in the lymph node staging of PCa.

Evidence acquisition

A Medline, Web of Knowledge, and Google Scholar search was carried out to select English-language articles published before January 2012 that discussed the diagnostic performance of choline PET to individualise lymph node disease at initial staging in PCa patients. Articles were included only if absolute numbers of true-positive, true-negative, false-positive, and false-negative test results were available or derivable from the text and focused on lymph node metastases. Reviews, clinical reports, and editorial articles were excluded. All complete studies were reviewed; thus qualitative and quantitative analyses were performed.

Evidence synthesis

From the year 2000 to January 2012, we found 18 complete articles that critically evaluated the role of choline PET and PCa at initial staging. The meta-analysis was carried out and consisted of 10 selected studies with a total of 441 patients. The meta-analysis provided the following results: pooled sensitivity 49.2% (95% confidence interval [CI], 39.9–58.4) and pooled specificity 95% (95% CI, 92–97.1). The area under the curve was 0.9446 (p < 0.05). The heterogeneity ranged between 22.7% and 78.4%. The diagnostic odds ratio was 18.999 (95% CI, 7.109–50.773).

Conclusions

Choline PET and PET/CT provide low sensitivity in the detection of lymph node metastases prior to surgery in PCa patients. A high specificity has been reported from the overall studies. Studies carried out on a larger scale with a homogeneous patient population together with the evaluation of cost effectiveness are warranted.  相似文献   

9.
Background: The aim of this study was to assess the capacity of positron emission tomography (PET) with fluorodeoxyglucose (FDG) to determine axillary lymph node status in patients with breast cancer undergoing sentinel node (SN) biopsy.Methods: Thirty-two patients with breast cancer and clinically negative axillary nodes were recruited. All patients underwent FDG-PET before SN biopsy. After SN biopsy, all patients underwent complete axillary lymph node (ALN) dissection.Results: The SNs were identified in all patients. Fourteen patients (43.8%) had metastatic SNs (macrometastatic in seven, micrometastatic in six, and isolated tumor cells in one). The false-negative rate of SN biopsy was 6.6% (1 in 15). FDG-PET identified lymph node metastases in 3 of the 14 patients with positive SNs. The overall sensitivity, specificity, and positive and negative predictive values of FDG-PET in the diagnosis of axillary metastasis were 20%, 100%, 100%, and 58.6%, respectively. No false-positive findings were obtained with FDG-PET.Conclusions: This study demonstrates the limitations of FDG-PET in the detection of ALN metastases in patients with early breast cancer. In contrast, FDG-PET seems to be a specific method for staging the axilla in breast cancer. SN biopsy can be avoided in patients with positive FDG-PET, in whom complete ALN dissection should be the primary procedure.  相似文献   

10.
《European urology》2023,83(3):212-221
BackgroundPatients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have a high risk of progression to metastatic disease, particularly if their prostate-specific antigen doubling time (PSADT) is ≤6 mo. However, patients remain at a high risk with a PSADT of >6 mo.ObjectiveTo evaluate the efficacy and safety of darolutamide versus placebo in patients stratified by PSADT >6 or ≤6 mo.Design, setting, and participantsA planned subgroup analysis of a global multicenter, double-blind, randomized, phase 3 trial in men with nmCRPC and PSADT ≤10 mo was conducted.InterventionPatients were randomized 2:1 to oral darolutamide 600 mg twice daily or placebo, while continuing androgen-deprivation therapy.Outcome measurements and statistical analysisThe primary endpoint was metastasis-free survival (MFS). Secondary endpoints were overall survival (OS) and times to pain progression, first cytotoxic chemotherapy, and symptomatic skeletal events. Quality of life (QoL) was measured using validated prostate-relevant tools. Safety was recorded throughout the study.Results and limitationsOf 1509 patients enrolled, 469 had PSADT >6 mo (darolutamide n = 286; placebo n = 183) and 1040 had PSADT ≤6 mo (darolutamide n = 669; placebo n = 371). Baseline characteristics were balanced between subgroups. Darolutamide significantly prolonged MFS versus placebo in both subgroups (unstratified hazard ratio [95% confidence interval]: PSADT >6 mo, 0.38 [0.26–0.55]; PSADT ≤6 mo, 0.41 [0.33–0.52]). OS and other efficacy and QoL endpoints favored darolutamide with significant improvement over placebo in both subgroups. The incidence of adverse events, including events commonly associated with androgen receptor inhibitors (fractures, falls, hypertension, and mental impairment), and discontinuations due to adverse events were low and similar to placebo. Limitations include small subgroup populations.ConclusionsIn patients with nmCRPC and PSADT >6 mo (maximum 10 mo), darolutamide provided a favorable benefit/risk ratio, characterized by significant improvements in MFS, OS, and other clinically relevant endpoints; maintenance of QoL; and favorable tolerability.Patient summaryIn patients with prostate cancer that has stopped responding to standard hormonal therapy (indicated by an increase in prostate-specific antigen [PSA] levels), there is a risk that the cancer will spread to other parts of the body. This risk is highest when the time it takes for the PSA level to double (ie, “PSA doubling time” [PSADT]) is less than 6 mo. However, there is still a risk that the cancer will spread even if the PSADT is longer than 6 mo. In a group of patients whose PSADT was more than 6 mo but no more than 10 mo, treatment with darolutamide slowed the cancer spread and allowed them to live longer than patients who received placebo (inactive drug). Darolutamide treatment did not cause many side effects and helped maintain patients’ quality of life without disruptions.  相似文献   

11.
12.

Background

The current recommendation of using transrectal ultrasound-guided biopsy (TRUSB) to diagnose prostate cancer misses clinically significant (CS) cancers. More sensitive biopsies (eg, template prostate mapping biopsy [TPMB]) are too resource intensive for routine use, and there is little evidence on multiparametric magnetic resonance imaging (MPMRI).

Objective

To identify the most effective and cost-effective way of using these tests to detect CS prostate cancer.

Design, setting, and participants

Cost-effectiveness modelling of health outcomes and costs of men referred to secondary care with a suspicion of prostate cancer prior to any biopsy in the UK National Health Service using information from the diagnostic Prostate MR Imaging Study (PROMIS).

Intervention

Combinations of MPMRI, TRUSB, and TPMB, using different definitions and diagnostic cut-offs for CS cancer.

Outcome measurements and statistical analysis

Strategies that detect the most CS cancers given testing costs, and incremental cost-effectiveness ratios (ICERs) in quality-adjusted life years (QALYs) given long-term costs.

Results and limitations

The use of MPMRI first and then up to two MRI-targeted TRUSBs detects more CS cancers per pound spent than a strategy using TRUSB first (sensitivity = 0.95 [95% confidence interval {CI} 0.92–0.98] vs 0.91 [95% CI 0.86–0.94]) and is cost effective (ICER = £7,076 [€8350/QALY gained]). The limitations stem from the evidence base in the accuracy of MRI-targeted biopsy and the long-term outcomes of men with CS prostate cancer.

Conclusions

An MPMRI-first strategy is effective and cost effective for the diagnosis of CS prostate cancer. These findings are sensitive to the test costs, sensitivity of MRI-targeted TRUSB, and long-term outcomes of men with cancer, which warrant more empirical research. This analysis can inform the development of clinical guidelines.

Patient summary

We found that, under certain assumptions, the use of multiparametric magnetic resonance imaging first and then up to two transrectal ultrasound-guided biopsy is better than the current clinical standard and is good value for money.  相似文献   

13.

Background

Prostate-specific antigen (PSA) testing has limited accuracy for the early detection of prostate cancer (PCa).

Objective

To assess the value added by percentage of free to total PSA (%fPSA), prostate cancer antigen 3 (PCA3), and a kallikrein panel (4k-panel) to the European Randomised Study of Screening for Prostate Cancer (ERSPC) multivariable prediction models: risk calculator (RC) 4, including transrectal ultrasound, and RC 4 plus digital rectal examination (4+DRE) for prescreened men.

Design, setting, and participants

Participants were invited for rescreening between October 2007 and February 2009 within the Dutch part of the ERSPC study. Biopsies were taken in men with a PSA level ≥3.0 ng/ml or a PCA3 score ≥10. Additional analyses of the 4k-panel were done on serum samples.

Outcome measurements and statistical analysis

Outcome was defined as PCa detectable by sextant biopsy. Receiver operating characteristic curve and decision curve analyses were performed to compare the predictive capabilities of %fPSA, PCA3, 4k-panel, the ERSPC RCs, and their combinations in logistic regression models.

Results and limitations

PCa was detected in 119 of 708 men. The %fPSA did not perform better univariately or added to the RCs compared with the RCs alone. In 202 men with an elevated PSA, the 4k-panel discriminated better than PCA3 when modelled univariately (area under the curve [AUC]: 0.78 vs 0.62; p = 0.01). The multivariable models with PCA3 or the 4k-panel were equivalent (AUC: 0.80 for RC 4+DRE). In the total population, PCA3 discriminated better than the 4k-panel (univariate AUC: 0.63 vs 0.56; p = 0.05). There was no statistically significant difference between the multivariable model with PCA3 (AUC: 0.73) versus the model with the 4k-panel (AUC: 0.71; p = 0.18). The multivariable model with PCA3 performed better than the reference model (0.73 vs 0.70; p = 0.02). Decision curves confirmed these patterns, although numbers were small.

Conclusions

Both PCA3 and, to a lesser extent, a 4k-panel have added value to the DRE-based ERSPC RC in detecting PCa in prescreened men.

Patient summary

We studied the added value of novel biomarkers to previously developed risk prediction models for prostate cancer. We found that inclusion of these biomarkers resulted in an increase in predictive ability.  相似文献   

14.
《European urology》2023,83(3):267-293
BackgroundInnovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management.ObjectiveTo present consensus voting results for select questions from APCCC 2022.Design, setting, and participantsBefore the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members (“panellists”) who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1–3.Outcome measurements and statistical analysisConsensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement.Results and limitationsThe voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis.ConclusionsThese voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials.Patient summaryThe Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions.  相似文献   

15.

Context

The role of positron emission tomography (PET) and PET/computed tomography (PET/CT) in prostate cancer (PCa) imaging is still debated, although guidelines for their use have emerged over the last few years.

Objective

To systematically review and conduct a meta-analysis of the available evidence of PET and PET/CT using 11C-choline and 18F-fluorocholine as tracers in imaging PCa patients in staging and restaging settings.

Evidence acquisition

PubMed, Embase, and Web of Science (by citation of reference) were searched. Reference lists of review articles and included articles were checked to complement electronic searches.

Evidence synthesis

In staging patients with proven but untreated PCa, the results of the meta-analysis on a per-patient basis (10 studies, n = 637) showed pooled sensitivity, specificity, and diagnostic odds ratio (DOR) of 84% (95% confidence interval [CI], 68–93%), 79% (95% CI, 53–93%), and 20.4 (95% CI, 9.9–42.0), respectively. The positive and negative likelihood ratios were 4.02 (95% CI, 1.73–9.31) and 0.20 (95% CI, 0.11–0.37), respectively. On a per-lesion basis (11 studies, n = 5117), these values were 66% (95% CI, 56–75%), 92% (95% CI, 78–97%), and 22.7 (95% CI, 8.9–58.0), respectively, for pooled sensitivity, specificity, and DOR; and 8.29 (95% CI, 3.05–22.54) and 0.36 (95% CI, 0.29–0.46), respectively, for positive and negative likelihood ratios. In restaging patients with biochemical failure after local treatment with curative intent, the meta-analysis results on a per-patient basis (12 studies, n = 1055) showed pooled sensitivity, specificity, and DOR of 85% (95% CI, 79–89%), 88% (95% CI, 73–95%), and 41.4 (95% CI, 19.7–86.8), respectively; the positive and negative likelihood ratios were 7.06 (95% CI, 3.06–16.27) and 0.17 (95% CI, 0.13–0.22), respectively.

Conclusions

PET and PET/CT imaging with 11C-choline and 18F-fluorocholine in restaging of patients with biochemical failure after local treatment for PCa might help guide further treatment decisions. In staging of patients with proven but untreated, high-risk PCa, there is limited but promising evidence warranting further studies. However, the current evidence shows crucial limitations in terms of its applicability in common clinical scenarios.  相似文献   

16.
17.

Background

The performance characteristics of serum prostate-specific antigen (PSA) as a diagnostic test for prostate cancer (PCa) are poor. The performance of the PCa antigen 3 (PCA3) gene as a primary diagnostic is unknown.

Objective

Assess the value of PCA3 as a first-line diagnostic test.

Design, setting and participants

Participants included men aged 63–75 who were invited for rescreening in the period from September 2007 to February 2009 within the European Randomised Study of Screening for Prostate Cancer, Rotterdam section.

Interventions

Lateral sextant biopsies were performed if the serum PSA value was ≥3.0 ng/ml and/or the PCA3 score was ≥10.

Measurements

Measurements included distribution and correlation of PSA value and PCA3 score and their relation to the number of cases and the characteristics of PCa detected. Additional value of PCA3 was included in men with previous negative biopsy and/or PSA <3.0 ng/ml.

Results and limitations

In 721 men, all biopsied, 122 PCa cases (16.9%) were detected. Correlation between PSA and PCA3 is poor (Spearman rank correlation: ρ = 0.14; p < 0.0001). A PSA ≥3.0 ng/ml misses 64.7% of the total PCa that can be detected with the sextant biopsy technique and 57.9% of serious PCa (T2a or higher and/or Gleason grade ≥4, n = 19), and 68.2% of biopsies could have been avoided; the respective data for PCA3 ≥35 are 32%, 26.3%, and 51.7%. Performance of PCA3 in men with low PSA (area under the curve [AUC]: 0.63) and/or previous negative biopsy (AUC: 0.68) is unclear but has limited reliability due to small numbers.

Conclusions

PCA3 as a first-line screening test shows improvement of the performance characteristics and identification of serious disease compared with PSA in this prescreened population.  相似文献   

18.
《European urology》2020,77(4):494-500
BackgroundLATITUDE, a randomized, double-blind trial, compared abiraterone acetate and prednisone (AAP) + androgen deprivation therapy (ADT) versus placebo (PBO) + ADT in high-risk metastatic castration-sensitive prostate cancer (mCSPC).ObjectiveTo assess the correlation of prostate-specific antigen (PSA) kinetics with overall survival (OS) and radiological progression-free survival (rPFS).Design, setting, and participantsA post hoc analysis of data from 597 men receiving AAP + ADT and 602 receiving PBO + ADT.Outcome measurements and statistical analysisThe associations of PSA-related outcomes (rates of confirmed 50% [PSA50] and 90% [PSA90] decline from baseline PSA [Prostate Cancer Working Group 2 criteria], rates of PSA < 0.2 ng/ml, median nadir PSA, time to PSA nadir [TPN], and time to PSA progression [TPP] with long-term outcomes [OS and rPFS]) were evaluated. Hazard ratios (HRs) were estimated using Cox proportional hazard model. Correlations of TPP with coprimary endpoints rPFS and OS were evaluated using Kendall’s tau (KT).Results and limitationsAAP + ADT significantly delayed median TPP versus PBO + ADT (33.2 vs 7.4 mo; HR: 0.3, p < 0.001). TPP correlated with rPFS (KT = 0.921) and OS (KT = 0.666). In the AAP + ADT group, 91% had PSA50 and 79% had PSA90 responses (relative risk [RR]: 1.36 and 2.30, respectively; p < 0.001 for both comparisons vs PBO + ADT). Compared with nonresponders, PSA50 and PSA90 responders had reduced risk of death (RR: 0.44 and 0.12, respectively). At 6 mo, 40% receiving AAP + ADT and 6.5% receiving PBO + ADT achieved PSA ≤0.1 ng/ml, which was significantly associated with longer rPFS and OS. Median nadir PSA was 0.09 ng/ml with AAP + ADT versus 2.36 ng/ml with PBO + ADT. Median TPN (AAP + ADT, 6.4 mo; PBO + ADT, 3.8 mo) positively correlated with rPFS and OS.ConclusionsSuperior PSA response dynamics with AAP + ADT versus ADT + PBO strongly correlated with long-term outcomes of rPFS and OS in high-risk mCSPC.Patient summaryWe found that low prostate-specific antigen levels (≤0.1 ng/ml) after 6 mo may indicate a good long-term response to treatment. Our results need confirmation.  相似文献   

19.
A multidisciplinary approach is necessary to manage advanced prostate cancer. The Advanced Prostate Cancer Consensus Conference (APCCC) in 2019 provided a practical guide to help clinicians consider therapeutic options in controversial areas, but healthcare systems vary across the world. At the 109th annual meeting of the Japanese Urological Association in December 2021, Japanese urologists voted on the questions in the APCCC 2019 guidelines regarding prostate-specific membrane antigen-positron emission tomography (PSMA-PET), management of oligometastatic prostate cancer, management of nonmetastatic castration-resistant prostate cancer (CRPC), management of a primary tumor in metastatic settings, systemic treatment of newly diagnosed metastatic castration-sensitive prostate cancer (CSPC), management of metastatic CRPC (mCRPC), and tumor genomic testing. We summarize the “real-world” status of the management of advanced prostate cancer in Japan. Several differences were noted in the management of advanced prostate cancer between Japanese urologists and the APCCC 2019 guidelines. Many Japanese urologists chose conventional imaging modalities for detecting metastasis instead of PSMA-PET. More Japanese urologists prefer androgen-deprivation therapy (ADT) alone in the management of low-volume metastatic CSPC than the APCCC panelists do, In the management of M0 CRPC, darolutamide and enzalutamide were chosen more by Japanese urologists than by the voters at the APCCC 2019. Bicalutamide remains one of the options for the management of mCRPC in Japan. More Japanese urologists do not recommend microsatellite instability (MSI) and BRCA1/2 tests than the voters at the APCCC 2019. Clinical evidence in Japan should be collected to address these discrepancies  相似文献   

20.
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