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1.
IntroductionThe purpose of this study was to evaluate the biopsy histology of men who underwent transperineal multi-parametric magnetic resonance imaging (mpMRI)/transrectal ultrasound fusion biopsy for Prostate Imaging Reporting and Data System (PI-RADS) score 5 lesions.Patients and MethodsFrom January 2016 to June 2019, 105 men with PI-RADS score 5 underwent mpMRI/transrectal ultrasound fusion biopsy combined with systematic prostate biopsy. All the patients underwent a 3.0 Tesla pelvic mpMRI for the first time before prostate biopsy. In detail, the detection rate for clinically significant prostate cancer (PCa) and the follow-up of the patients without proven diagnosis of PCa has been reported.ResultsIn 91 (86.7%) of 105 patients, a stage T1c PCa was diagnosed, and 89 (84.5%) of 105 of them were classified as clinically significant PCa. Among the 16 (15.5%) of 105 patients with absence of cancer, 5 (31.5%) of 16 had an aspecific granulomatous prostatitis, 1 (6.2%) of 16 had a specific granulomatous prostatitis secondary to prostatic Mycobacterium Tubercolosis, and 10 (62.3%) of 16 had a diagnosis of normal parenchyma. The 6 patients with granulomatous prostatitis underwent specific antibiotic therapy followed by laboratory (ie, semen and urine cultures) and clinical evaluation. Six months from prostate biopsy, none of the 16 patients underwent repeat prostate biopsy because prostate-specific antigen (PSA) (15/16 cases) plus PSA density significantly decreased; in addition, in all the cases the initial PI-RADS score 5 was downgraded at mpMRI revaluation to PI-RADS score ≤ 3.ConclusionThe reduction of PSA plus PSA density values and the downgrading of PI-RADS score to ≤ 3 allow avoiding a repeated prostate biopsy in men with initial mpMRI PI-RADS score 5 lesion and negative biopsy histology.  相似文献   

2.

Introduction

Multiparametric magnetic resonance imaging (mpMRI) is gaining acceptance to guide targeted biopsy (TB) in prostate cancer (PC) diagnosis. We aimed to compare the detection rate of software-assisted fusion TB (SA-TB) versus cognitive fusion TB (COG-TB) for PC and to evaluate potential clinical features in detecting PC and clinically significant PC (csPC) at TB.

Patients and Methods

This was a retrospective cohort study of patients with rising and/or persistently elevated prostate-specific antigen (PSA) undergoing mpMRI followed by either transperineal SA-TB or transrectal COG-TB. The analysis showed a matched-paired analysis between SA-TB versus COG-TB without differences in clinical or radiological characteristics. Differences among detection of PC/csPC among groups were analyzed. A multivariable logistic regression model predicting PC at TB was fitted. The model was evaluated using the receiver operating characteristic-derived area under the curve, goodness of fit test, and decision-curve analyses.

Results

One hundred ninety-one and 87 patients underwent SA-TB or COG-TB, respectively. The multivariate logistic analysis showed that SA-TB was associated with overall PC (odds ratio [OR], 5.70; P < .01) and PC at TB (OR, 3.00; P < .01) but not with overall csPC (P = .40) and csPC at TB (P = .40). A nomogram predicting PC at TB was constructed using the Prostate Imaging Reporting and Data System version 2.0, age, PSA density and biopsy technique, showing improved clinical risk prediction against a threshold probability of 10% with a c-index of 0.83.

Conclusion

In patients with suspected PC, software-assisted biopsy detects most cancers and outperforms the cognitive approach in targeting magnetic resonance imaging-visible lesions. Furthermore, we introduced a prebiopsy nomogram for the probability of PC in TB.  相似文献   

3.

Purpose

To understand the multiparametric magnetic resonance imaging (mpMRI) interreader agreement between radiologists of peripheral and academic centers and the possibility to avoid prostate biopsies according to magnetic resonance imaging second opinion.

Patients and Methods

This prospective observational study enrolled 266 patients submitted to mpMRI at nonacademic centers for cancer detection or at active surveillance begin. Images obtained were reviewed by 2 unblinded radiologists with 8 and 5 years’ experience on mpMRI, respectively. We recorded Prostate Imaging Reporting and Data System (PI-RADS) v2 categories and management strategy changes after mpMRI rereadings. Interreader agreement was assessed by the Cohen kappa. For mpMRI second opinion, positive predictive value and negative predictive value were calculated.

Results

In the original readings, no lesions (ie, PI-RADS < 2) were observed in 17 cases (6.5%). Reported index lesion (IL) PI-RADS category was 2 in 23 (8.5%), 3 in 85 (32%), 4 in 98 (37%), and 5 in 13 (5%) men, respectively. It is noteworthy that in 30 examinations (11%), an IL was recognized by radiologists, but a suspicious score was not assigned. According to first reading of mpMRI, initial clinical strategy included performing a targeted (226; 85%) or a systematic biopsy (8; 3%), scheduling the patient to an active surveillance program without repeat biopsy (10; 4%), or monitoring prostate-specific antigen without prostate sampling (22; 8%). The mpMRI rereads did not change IL PI-RADS category in 91 cases (38.5%), although in 20 (8.5%) and 125 (53%) IL PI-RADS was upgraded or downgraded, respectively (κ = 0.23). The clinical management changed in 113 patients (48%) (κ = 0.2). Overall, 102 targeted biopsies (51%) were avoided and 72 men (34.5%) were not submitted to biopsy after mpMRI second opinion. Positive predictive value and negative predictive value of the mpMRI rereading were 58% and 91%, respectively. Major limitations of the study are limited-time follow-up and the lack of a standard of reference for some men, who were not submitted to biopsy according to mpMRI second opinion.

Conclusion

There is an important level of discordance between mpMRI reports. According to imaging second opinion, roughly half of targeted biopsies could be avoidable and 34.5% of men could skipped prostate sampling. Prospective randomized trials are needed to confirm our findings.  相似文献   

4.

Background

There is a lack of real-world data regarding the treatment outcomes of chemohormonal therapy versus hormonal therapy alone in Chinese men with metastatic hormone-sensitive prostate cancer.

Patients and Methods

We conducted a territory-wide, multicenter, age- and prostate-specific antigen (PSA)-matched cohort study comparing chemohormonal therapy and hormonal therapy alone in Chinese men with metastatic hormone-sensitive prostate cancer. Patient and disease characteristics were reviewed. The primary outcome was PSA progression-free survival. Secondary outcomes included clinical progression-free survival and castration resistance-free survival. Kaplan-Meier and multivariate Cox regression analyses were performed.

Results

From January 2015 to July 2016, 32 Chinese men with metastatic hormone-sensitive prostate cancer were treated with chemohormonal therapy, and they were matched to 32 Chinese men who were treated with hormonal therapy alone. Patient and disease characteristics were similar between the 2 groups. The chemohormonal therapy group had a significantly better PSA progression-free survival (P = .001) and castration resistance-free survival (P = .002) than the hormonal therapy group. There was no significant difference in the clinical progression-free survival between the 2 groups. Upon multivariate Cox regression analyses, the use of chemohormonal therapy was significantly associated with a longer time to PSA progression (hazard ratio, 0.31; 95% confidence interval, 0.31-0.73; P = .008) and a longer time to castration resistance (hazard ratio, 0.38; 95% confidence interval, 0.17-0.83; P = .015), but was not associated with clinical progression.

Conclusions

The use of chemohormonal therapy could prevent PSA progression and the development of castration resistance when compared with hormonal therapy alone in Chinese men with metastatic hormone-sensitive prostatic cancer.  相似文献   

5.

Background

Patients with biochemically recurrent prostate cancer and short prostate-specific antigen doubling time (PSADT) are at risk for metastasis yet may wish to avoid androgen deprivation therapy. Itraconazole may have antitumor activity without affecting circulating androgen levels. We therefore evaluated itraconazole as a potentially noncastrating treatment approach in biochemically recurrent prostate cancer.

Patients and Methods

Patients with biochemically recurrent prostate cancer and PSADT ≤ 15 months, with serum testosterone > 150 ng/dL, were prospectively enrolled. The primary end point was the proportion of patients who experienced ≥ 50% decline from baseline in serum prostate-specific antigen (PSA) by week 12.

Results

Twenty-one patients were enrolled. The median (range) age, baseline PSA, and PSADT at study entry was 72 (49-76) years, 7.6 (1.5-45.5) ng/mL, and 5.7 (1.2-13.0) months, respectively. Among 19 patients with evaluable data, 1 patient (5%) had a > 50% PSA decline. Nine patients (47%) experienced any PSA decline (mean decline 25.0%, range 2%-60%) by week 12. Among 10 patients without a PSA decline, the on-treatment versus pretreatment PSADT was not significantly longer (median 6.8 vs. 4.3 months, P = .17). There was no significant change from baseline to week 12 in serum testosterone (median change = 32.4%, P = .21) or androstenedione (median change = ?8.3%, P = .85). The most common adverse events were edema (52%), fatigue (38%), hypertension (24%), and hypokalemia (24%).

Conclusion

Itraconazole modulates serum PSA levels without lowering serum testosterone. However, the magnitude of effect is modest, and treatment carries risk of toxicities associated with mineralocorticoid excess.  相似文献   

6.

Background

Overexpression of periostin (POSTN) is associated with prostate cancer (PCa) aggressiveness. We investigated the prognostic significance of POSTN expression in tumor biopsy samples of patients with PCa.

Methods

We scored POSTN expression by immunohistochemistry analysis on 215 PCa biopsy samples using an anti–POSTN-specific antibody. A total immunoreactive score (T-IRS) was calculated by adding the POSTN staining scores of stromal and epithelial tumor cells. Prostate-specific antigen (PSA) progression/recurrence-free survival (PFS), radiographic progression/recurrence-free survival (rPFS), and overall survival (OS) were the study end points.

Results

A total of 143 patients received therapy with radical attempt, whereas 72 had locally advanced or metastatic disease and received hormone therapy alone. Median T-IRS was 9 and 12 (range, 0-20), respectively (P = .001). Overall, we found a weak positive correlation of T-IRS with prebiopsy PSA levels (r = 0.166, P = .016) and Gleason score (r = 0.266, P < .000). T-IRS ≥ 8 independently predicted for shorter PSA-PFS and OS (hazard ratio [HR] [95% confidence interval (CI)] ≥ 8 versus < 8: 1.50 [1.06-2.14], P = .024 and 1.92 [1.20-3.07], P = .007, respectively). In the subgroup analysis, the association between T-IRS and patient outcome was retained in patients who received therapy with radical attempt (HR [95% CI] ≥ 8 vs. < 8: rPFS: 2.06 [1.18-3.58], P = .01; OS: 2.36 [1.24-4.50], P = .009) and in those with low to intermediate Gleason scores (HR [95% CI] ≥ 8 vs. < 8: PSA-PFS: 1.65 [1.06-2.59], P = .028; rPFS: 2.09 [1.14-3.87], P = .018; OS: 2.57 [1.31-5.04], P = .006).

Conclusion

POSTN T-IRS on PCa biopsy samples independently predicted the risk of recurrence, progression, and death in patients with localized disease and in those with low to intermediate Gleason scores.  相似文献   

7.

Background

Anterior zone (AZ) disease is present in one-fifth of men with newly diagnosed prostate cancer and has been associated with poor pathologic features. However, anterior targeted biopsies are not a routine part of active surveillance (AS) protocols. Our purpose is to assess the utility of AZ sampling for prostate biopsy in patients undergoing surveillance for low-risk prostate cancer.

Methods

A prospective data collection of men enrolled in AS between 2006 and 2014 was performed. Patient and disease characteristics were collected, including number of positive cores and Gleason score on all diagnostic and surveillance biopsies. Progression was defined as incident Gleason > 6 in any core and/or receipt of definitive therapy including radical prostatectomy or radiotherapy. Rate of anterior disease and relationship to subsequent disease progression was assessed.

Results

A total of 85 men were included, of which 45% demonstrated progression. Median follow-up was 40 months. Among those undergoing AZ sampling at initial diagnosis, 37% presented with AZ disease. A total of 47% of men with AZ-only disease progressed, whereas 78% of men with AZ and peripheral zone disease progressed. This compares with a 39% rate of progression among men with only peripheral zone disease. Multivariable logistic regression identified increasing body mass index as a significant predictor of disease progression (odds ratio, 5.18; 95% confidence interval, 1.06-25.31; P = .04).

Conclusions

Over one-third of men enrolled in AS for low-risk prostate cancer had AZ disease on diagnostic biopsy. Progression occurred in the majority of these men. AZ sampling should be considered in biopsy surveillance strategies.  相似文献   

8.

Background

177Lu–PSMA-617 (Lu-PSMA) is an emerging therapy in men with metastatic castration-resistant prostate cancer. Paired theranostic agents have the potential to visually identify phenotypes that will respond to targeted therapy. This study examined the value of 68Ga-HBEDD PSMA-11; prostate-specific membrane antigen (PSMA) positron emission tomography (PET) in predicting treatment response and disease progression in Lu-PSMA therapy within the context of a phase 2 prospective pilot trial.

Patients and Methods

Men with progressive, symptomatic metastatic castration-resistant prostate cancer previously treated with antiandrogens (abiraterone and/or enzalutamide) and taxane-based chemotherapy were prospectively enrolled. Eligibility criteria included uptake on PSMA PET above or equal to liver activity, with no 18F-Fluoro–deoxyglucose (FDG) PET-discordant disease. Men received up to 4 cycles of Lu-PSMA at 6 weekly intervals. Repeat FDG/PSMA PET imaging was performed after completion of therapy or at prostate-specific antigen (PSA) progression. The study assessed treatment response to Lu-PSMA using PSA response and correlated treatment response (PSA) to molecular imaging parameters at enrollment.

Results

Fourteen of 18 men screened underwent Lu-PSMA therapy. Ten (71%) of 14 had a PSA response (mean reduction, 59%). A ≥ 50% reduction in PSA occurred in 5 (36%), and ≥ 30% in 9 (64%). PSMA PET standardized uptake value (SUV) at screening was predictive of ≥ 30% PSA reduction: SUV max value 17 ± 9 versus 44 ± 15 (P < .007), and PSMA SUV mean 6 ± 4 versus 10 ± 4 (P < .04). FDG parameters alone, and volume or site of disease did not predict PSA response. No imaging parameters predicted ≥ 50% PSA reduction. Nine of 14 men were reimaged after treatment, revealing 3 distinct patterns of progression.

Conclusion

PSMA PET plays an important role in predicting treatment response to Lu-PSMA and in identifying subsequent patterns of failure, which may aid in determining the next best treatment options.  相似文献   

9.

Background

The safety of active surveillance (AS) for Gleason 6 favorable intermediate-risk (FIR) prostate cancer is unknown. To provide guidance, we examined the incidence and predictors of upgrading or upstaging for Gleason 6 FIR patients treated with radical prostatectomy.

Patients and Methods

We identified 2807 men in the National Cancer Database diagnosed from 2010 to 2012 with Gleason 6 FIR disease (<50% positive biopsy cores [PBC] with either prostate-specific antigen [PSA] of 10-20 ng/mL or cT2b-T2c disease) treated with radical prostatectomy. Logistic regression was used to identify predictors of upgrading (Gleason 3+4 with tertiary Gleason 5 or Gleason ≥4+3) or upstaging (pT3-4/N1).

Results

Fifty-seven percent of the cohort had PSA of 10 to 20 ng/mL; 25.5% patients with PSA of 10 to 20 ng/mL and 12.4% with cT2b to T2c disease were upgraded or upstaged. In multivariable analysis, predictors of upgrading or upstaging included increasing age (P = .026), PSA (P = .001), and percent PBC (P < .001), and black race versus white (P = .035) for patients with PSA of 10 to 20 ng/mL and increasing PSA (P = .001) and percent PBC (P < .001) for patients with cT2b to T2c disease. Men with PSA of 15.0 to 20.0 ng/mL or 37.5% to 49.9% PBC with PSA of 10 to 20 ng/mL had >30% risk of upgrading or upstaging, whereas cT2b to T2c patients with <12.5% PBC or PSA <5.0 ng/mL had <10% risk.

Conclusion

We found that Gleason 6 FIR patients with cT2b to T2c tumors had a low risk of harboring higher grade or stage disease and would be reasonable AS candidates, whereas patients with PSA of 10 to 20 ng/mL had a high risk and might generally be poor AS candidates.  相似文献   

10.

Background

Inflammation and infections have been associated with prostate cancer progression. We assessed whether elevated serum cytokines or T. vaginalis seropositivity at the time of diagnosis was associated with higher grade or lethal prostate cancer.

Patients and Methods

Men with localized or metastatic prostate cancer were included in this study. Cytokine serum levels including interleukin (IL)-1α, IL-1β, IL-2, IL-6, IL-8, monocyte chemotactic protein 1 (CCL-2), tumor necrosis factor α, and growth-regulated oncogene α (CXCL-1) using a multiplex enzyme-linked immunosorbent assay and T. vaginalis serology were measured in blood samples at diagnosis.

Results

A total of 324 patients were identified at time of localized disease and 118 at time of metastatic disease. Of the 189 patients with localized disease and clinical follow-up data (median, 73 months), 28 developed lethal disease. There was no association between circulating cytokine levels above median concentrations nor T. vaginalis seropositivity and risk of intermediate- to high-risk or lethal prostate cancer.

Conclusion

Higher levels of serum cytokine levels and T. vaginalis seropositivity at diagnosis are not associated with high-grade or lethal prostate cancer and do not aid risk stratification of localized prostate cancer.  相似文献   

11.

Background

We retrospectively assessed the clinical significance of the Prostate Imaging Reporting and Data System (PI-RADS), version 2, criteria based on biparametric magnetic resonance imaging (bp-MRI), together with the International Society of Urological Pathology (ISUP) grade, for predicting biochemical recurrence (BCR) after radical prostatectomy.

Materials and Methods

The data from 126 patients who had undergone radical prostatectomy were retrospectively analyzed. The prognostic significance of the PI-RADS v2 score based on bp-MRI was assessed with other clinical factors, including the ISUP grade. We defined a positive PI-RADS and ISUP score as ≥ 4 and ≥ 3, respectively. Statistical analysis was performed using Cox proportional hazard models, logistic regression analysis, and the Kaplan-Meier method.

Results

The median age and median prostate-specific antigen level were 66 years and 7.96 ng/mL, respectively. The number of positive PI-RADS scores was 106 (84.1%) and the number of positive ISUP grade scores was 71 (56.3%). PI-RADS ≥ 4 (P = .0031) and ISUP ≥ 3 (P = .070) were the 2 independent prognostic factors predictive of BCR. A positive PI-RADS score was related to tumor volume (P = .014), and a positive ISUP score was related to prostate-specific antigen level (P = .043), extraprostatic extension (P = .029), and Gleason upgrading (P < .0001). After stratifying patients into risk groups according to PI-RADS and ISUP positivity, the poor-risk group (PI-RADS and ISUP grade positive) showed significantly worse BCR-free survival compared with that of the favorable- and intermediate-risk groups (P < .0001), with a median survival difference of 21 months.

Conclusion

Biparametric PI-RADS v2 and ISUP grade criteria predicted for BCR after radical prostatectomy. PI-RADS v2 combined with the ISUP grade might be helpful in choosing the treatment modality of patients with localized prostate cancer.  相似文献   

12.
IntroductionMagnetic resonance imaging (MRI)-ultrasound fusion targeted prostate biopsy (FB) has been advocated by many experts as a replacement for the standard template biopsy. Herein, we compared pathology results and cancer detection rates of FB with our standard 14-core systematic prostate biopsy (SB) that includes 2 anterior cores.Materials and MethodsOne hundred two men with elevated prostate-specific antigen and suspicious lesions on multiparametric MRI, Prostate Imaging Reporting And Data System (PI-RADS) v2 score ≥ 3, underwent FB. Each target lesion was biopsied 3 times; our SB was performed concurrently. Biopsy results were compared for overall and clinically significant (cs), defined as Gleason score ≥ 7, cancer detection.ResultsFifty-two percent of patients had positive biopsy results, and of those, 44 had cs prostate cancer (PCa). The overall detection rates for FB and SB were 39% and 50%, respectively, and there was no statistical difference in the detection rate of csPCa detection rate (P = .42). Of 17 patients diagnosed with a high-risk PCa, defined as Gleason score ≥ 8, SB identified 15, whereas FB identified 10. Within the SB group, 21 had positive anterior core biopsies, of which 11 were cs.ConclusionExpanding the standard template prostate biopsies to include 2 anterior horn sampling may be just as effective as FB in men with PI-RADS lesion ≥ 3, thereby mitigating the increased cost associated with FB.  相似文献   

13.

Background

The rate of noninterventional treatment (NIT) in prostate cancer (PCa) active surveillance (AS) candidates is on the rise. However, contemporary data are unavailable. We described community-based NIT rates within 16 Surveillance Epidemiology and End Results (SEER) registries between 2010 and 2014.

Patients and Methods

We identified 23,360 PCa patients who fulfilled the University of California San Francisco AS criteria (prostate-specific antigen [PSA] < 10 ng/mL, clinical T stage ≤ T2a, Gleason score ≤ 6, and positive cores < 33%). Annual NIT rates as well as patient distribution according to PSA, age, number of positive cores, and clinical T stage were studied. Multivariable logistic regression analysis tested NIT predictors.

Results

Between 2010 and 2014, the NIT rate increased from 30.2% to 57.5% (P = .004). Within 16 SEER registries, NIT rates ranged from 25.9% to 62%. NIT rate increased uniformly within all examined registries. Of patient and tumor characteristics (PSA > 4 ng/mL, cT2a and > 1 positive core) only the proportion of NIT patients aged < 65 years increased over time from 47.3% to 53.2% (P = .03). By multivariable logistic regression analysis predicting NIT rate, older age (odd ratio [OR] = 1.05), more contemporary year of diagnosis (OR = 1.41), and being unmarried (OR = 1.45) and uninsured (OR = 2.41) were independent predictors.

Conclusion

The NIT rate has markedly increased across all examined SEER registries. Nonetheless, important differences distinguish those who received high-end NIT from low-end NIT. PCa characteristics of NIT patients remained unchanged over time. However, in addition to geographical differences in NIT rates, patient characteristics such as age, marital status, and insurance status represent potential NIT access barriers.  相似文献   

14.

Background

RAS and RAF mutations in colorectal cancer (CRC) hold value in precision medicine. Liquid biopsy is an alternative to tumor tissue biopsy, and circulating tumor DNA (ctDNA) has been intensively investigated, but the clinical relevance of RAS and RAF mutations in plasma is yet to be determined. This study aimed to investigate the clinical aspects of RAS/RAF mutations during combination treatment.

Patients and Methods

Patients with RAS/RAF tumor wild-type metastatic CRC treated with combination chemotherapy and an EGFR inhibitor were included. Blood samples were collected at baseline and every treatment cycle and analyzed for 31 RAS, RAF, and EGFR mutations until progressive disease or censoring using droplet digital PCR.

Results

Forty-six patients were prospectively enrolled onto the study. At baseline, 7% had detectable RAS/RAF mutations in ctDNA. During the treatment course, the fraction of patients with mutated ctDNA increased to 22%. The emergence of mutations did not correlate with response or risk of progression while receiving treatment (P = 1.0).

Conclusion

Emergence of plasma RAS/RAF mutations was not correlated with the effect of combination chemotherapy and EGFR inhibition in patients with RAS/RAF wild-type metastatic CRC.  相似文献   

15.

Background

The objective of the study was to evaluate the outcomes of clinically localized prostate cancer treated with prostatectomy versus radiation therapy within the context of a prospective prostate cancer screening study.

Patients and Methods

Within the PLCO (Prostate, Lung, Colorectal, and Ovary) trial, patients who were diagnosed with clinically localized prostate cancer and subsequently received treatment with prostatectomy or radiation therapy (with or without hormonal treatment) were included. Univariate and multivariate Cox regression analyses were then performed to determine factors affecting overall and prostate cancer-specific survival. Factors with P < .05 in univariate analysis were included in the multivariate analysis.

Results

A total of 3953 patients were included in the current analysis. These included 2044 patients treated with prostatectomy and 1909 patients treated with radiation therapy with or without hormonal treatment. In an adjusted multivariate analysis for factors affecting overall survival, prostatectomy was associated with better overall survival compared with radiation therapy (hazard ratio, 0.548; 95% confidence interval [CI], 0.440- 681; P < .001). Likewise, in an adjusted multivariate analysis for factors affecting prostate cancer-specific survival, prostatectomy was associated with better prostate cancer-specific survival compared with radiation therapy (hazard ratio, 0.485; 95% CI, 0.286- 0.822; P = .007). Similar findings were found with propensity score matching and repeating the same analyses on the post-matching cohort.

Conclusion

Prostatectomy seems to predict better overall and prostate cancer-specific survival compared with radiation therapy among patients with clinically localized prostate cancer diagnosed within the PLCO trial.  相似文献   

16.

Background

There is evidence linking metformin to improved prostate cancer–related outcomes.

Patients and Methods

Twenty-five men with metastatic castration-resistant prostate cancer and prostate-specific antigen (PSA) progression while receiving treatment with abiraterone from 3 Swiss centers were included in this single-arm phase 2 trial between November 2013 and September 2016. Metformin was added to abiraterone continuously at 1000 mg twice daily in uninterrupted 4-week cycles. The primary end point was the absence of disease progression at 12 weeks (PFS12). The Fleming single-stage design was applied. With a 5% significance level and 80% power, 25 patients were required to test PFS12 ≤ 15% (H0) compared to ≥ 35% (H1). Secondary end points included toxicity and safety issues. The study was registered at ClinicalTrials.gov (NCT01677897).

Results

The primary end point PFS12 was 12% (3 of 25 patients) (95% confidence interval, 3-31). Most patients had PSA progression, almost half had radiographic progression, but only 1 patient had symptomatic progression. Eleven (44%) of 25 patients had grade 1 and 2 patients each grade 2 (8%) or grade 3 (8%) gastrointestinal toxicity (nausea, diarrhea, loss of appetite). One patient discontinued treatment at week 5 because of intolerable grade 3 diarrhea.

Conclusion

The addition of metformin to abiraterone for patients with metastatic castration-resistant prostate cancer and PSA progression while receiving abiraterone therapy does not affect further progression and has no meaningful clinical benefit. A higher-than-expected gastrointestinal toxicity attributed to metformin was observed.  相似文献   

17.

Background

The study aimed to evaluate the feasibility and reliability of ultrasound-guided vacuum-assisted breast biopsy (US-VABB) for sampling of microcalcifications indicative of cancer when stereotactic vacuum-assisted breast biopsy cannot be performed because of reasons such as thin breast tissue, insufficient thickness at compression, and microcalcification situated close to the chest wall or in breast tissue of the axillary tail.

Patients and Methods

The study population was selected from among 187 patients with microcalcifications detected on mammogram. The findings were classified using the American College of Radiology criteria as Breast Imaging Reporting and Data System 3, 4, or 5. 30 Thirty were not eligible for stereotactic guidance because of reasons such as small breast size, compression thickness <2 cm, or microcalcification located in the axillary tails or close to chest wall. In 23 patients microcalcifications were detected at ultrasound, and US-VABB was performed. The other 7 patients underwent surgical biopsy. In the 23 patients who underwent US-VABB, multiple core samples were taken after a specimen mammography to ensure that microcalcifications were included.

Results

Biopsy was successful in all cases of US-VABB. The procedure was well tolerated, and there were no complications.

Conclusion

US-VABB should be preferred over diagnostic surgical biopsy when microcalcifications are sonographically visible and stereotactic guidance is contraindicated. The procedure appears to be reliable and accurate, with added advantages such as low cost and absence of radiation exposure.  相似文献   

18.

Introduction

Leptomeningeal metastases (LMs) indicated a poor prognosis in NSCLC. LMs were more frequent in driver gene–mutated patients, and cerebrospinal fluid (CSF) cell-free DNA has shown unique genetic profiles of LM in EGFR-mutated LM. However, studies in patients with ALK receptor tyrosine kinase gene (ALK)-rearranged NSCLC with LMs are scarce.

Methods

Patients with lung cancer with ALK rearrangement were screened from September 2011 to February 2018 at our institute. CSF and paired plasma were tested by next-generation sequencing.

Results

LMs were diagnosed in 30 (10.3%) of 291 patients with ALK-rearranged lung cancer. A total of 11 paired CSF and plasma samples tested by next-generation sequencing were analyzed. Driver genes were detected in 81.8% of the CSF samples (9 of 11) and 45.5% of the plasma samples (5 of 11) (p = 0.183). The maximum allelic fractions were all higher in CSF than in plasma (p = 0.009). ALK and tumor protein p53 gene (TP53) were the two most frequently mutated genes in CSF. Gatekeeper gene ALK G1202R and C1156F mutations were identified in CSF after resistance to alectinib. Multiple copy number variants were mainly found in CSF, including in EGFR, cyclin D1 gene (CCND1), fibroblast growth factor 3 gene (FGF3), and fibroblast growth factor 4 gene (FGF4). Also found were v-myc avian myelocytomatosis viral oncogene homolog gene (MYC) copy number gains and TP53 and cyclin dependent kinase inhibitor 2A gene (CDKN2A) copy number deletions. Brigatinib seemed to be effective in controlling LM. One case showed that CSF could be used to monitor disease development of LM and longitudinally monitor tumor response.

Conclusion

Liquid biopsy of CSF is more sensitive than liquid biopsy of plasma to detect targetable alterations, characterizing resistance mechanisms on progression and monitoring tumor response in patients with ALK-rearranged NSCLC with LM. Thus, CSF might be promising as a medium of liquid biopsy in LM.  相似文献   

19.

Aims

To evaluate the prevalence, patterns of care and outcome of pathologically node-positive (pN+) prostate cancer (P-Ca) after radical prostatectomy from a provincial population database.

Patients and methods

Patients were identified from a provincial cancer registry and a genitourinary cancer outcomes unit (2005–2014). Of a total of 4723 patients who underwent radical prostatectomy, 167 patients with pN+ P-Ca were identified (28/2181 from 2005–2007 and 139/2542 from 2010–2014). Persistently elevated postoperative prostate-specific antigen (PSA) ≥ 0.2 ng/ml was noted in 52 (31%) patients, 23 (44.2%) of whom had salvage androgen deprivation therapy plus radiotherapy (ADT + RT), 25 (48%) were managed with ADT alone and four (7.8%) had no treatment. Of 115 patients with postoperative PSA <0.2 ng/ml, 47 (41%) had ADT alone and 50 (43.5%) had ADT + RT. Survival estimation was carried out using the Kaplan–Meier method. The association of prognostic factors with survival was evaluated using univariate and multivariate analysis and was limited to the newer cohort (2010–2014).

Results

The median age was 64 years; the median baseline PSA was 12.5 ng/mL (range 2.5–108.4). After a median follow-up of 48 months, overall survival at 5 and 10 years for the entire cohort were 89% and 81%, respectively, and distant metastasis-free survival (DMFS) at the same time points were 77% and 58%, respectively. For the newer cohort, 5-year overall survival and DMFS were 91.5% and 76%, respectively. On univariate analysis, persistently elevated postoperative PSA ≥0.2 ng/ml (P = 0.0003), seminal vesicle involvement (P = 0.027), ≥2 nodes (P = 0.035) and ADT alone (P = 0.054) had a poor prognostic impact on DMFS, whereas margin involvement had a marginally negative influence on overall survival (P = 0.06). On multivariate analysis, postoperative PSA ≥0.2 ng/ml (hazard ratio 4.4, 95% confidence interval 1.7–11.4; P = 0.002) continued to have a significant association with DMFS. On a sensitivity analysis, postoperative PSA ≥0.1 also had a significant association with DMFS on univariate and multivariate analysis (hazard ratio 3.69, 95% confidence interval 1.32–10.29; P = 0.01). Similarly, postoperative PSA ≥0.4 ng/ml had a significant association with DMFS (hazard ratio 3.87, 95% confidence interval 1.58–9.46, P = 0.003).

Conclusion

This study showed a notable difference in the proportion of pN+ P-Ca patients between two different time cohorts. A significant association of persistently elevated postoperative PSA with DMFS was noted in our study. This must be accounted for while tailoring postoperative treatment in pN+ P-Ca.  相似文献   

20.
IntroductionMultiparametric magnetic resonance imaging (mpMRI) has been shown to have a good performance in predicting cancer among patients with a prostate-specific antigen (PSA) level of 4 to 10 ng/mL. However, lesion location on mpMRI has never been separately considered.Patients and MethodsPatients with PSA level of 4 to 10 ng/mL were prospectively enrolled and underwent transrectal ultrasound-guided prostate biopsy. Patient information was collected, and logistic regression analysis was performed to determine the predictive factors of clinically significant prostate cancer (csPCa). Patients were grouped by lesion location to determine the Prostate Imaging Reporting and Data System (PI-RADS) v2.1 cutoff value in predicting csPCa.ResultsAmong 222 patients, 121 were diagnosed with PCa and 92 had csPCa. Age, prostate volume, PSA density, location (peripheral zone, csPCa only), and PI-RADS v2.1 score were correlated with PCa and csPCa, and PI-RADS v2.1 score was the best predictor. A PI-RADS v2.1 score of 4 was the best cutoff value for predicting csPCa in patients with lesions only in the transitional zone with respect to the Youden index (0.5896) and negative predictive value (93.10%) with acceptable sensitivity (81.82%) and specificity (77.14%). An adjustment of the cutoff value to 3 for lesions in the peripheral zone would increase the negative predictive value (92.00%) and decrease the false negative rate (2.90%) with an acceptable sensitivity (97.10%) and specificity (30.67%).ConclusionPI-RADS v2.1 score is an effective predictor of csPCa in patients with PSA levels of 4 to 10 ng/mL. Patients with transitional zone or peripheral zone lesions should undergo biopsy if the PI-RADS v2.1 score is ≥ 4 or ≥ 3, respectively.  相似文献   

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