Flourodeoxyglucose positron emission tomography scan may be helpful in the case of ductal variant prostate cancer when prostate specific membrane antigen ligand positron emission tomography scan is negative

Gallium‐68 prostate specific membrane antigen ligand (Ga‐68 PSMA) positron emission tomography/computed tomography (PET/CT) scanning is emerging as a useful imaging modality for the staging of suspected and known recurrent or metastatic prostate cancer and in staging of newly diagnosed higher grade prostate cancer. However, we have observed at our institution that in some cases of the more aggressive ductal variant, Ga‐68 PSMA uptake has sometimes been poor compared with prominent 18‐flourodeoxyglucose (F‐18 FDG) avidity seen in F‐18 FDG PET/CT, which would suggest that FDG PET/CT scans are important in staging of ductal pattern prostate cancer.     

Incidental finding of ileal gastrointestinal stromal tumour during prostate cancer staging with prostate‐specific membrane antigen scan

Prostate‐specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is used in managing and staging prostate cancer, but can identify other non‐prostate pathology. We present the first reported case where small bowel gastrointestinal stromal tumour (GIST) has been incidentally identified on PSMA‐PET scan and highlight the need for awareness of other pathology being identified on PSMA‐PET/CT.     

Body mass index in relation to serum prostate‐specific antigen levels and prostate cancer risk

High Body mass index (BMI) has been directly associated with risk of aggressive or fatal prostate cancer. One possible explanation may be an effect of BMI on serum levels of prostate‐specific antigen (PSA). To study the association between BMI and serum PSA as well as prostate cancer risk, a large cohort of men without prostate cancer at baseline was followed prospectively for prostate cancer diagnoses until 2015. Serum PSA and BMI were assessed among 15,827 men at baseline in 2010–2012. During follow‐up, 735 men were diagnosed with prostate cancer with 282 (38.4%) classified as high‐grade cancers. Multivariable linear regression models and natural cubic linear regression splines were fitted for analyses of BMI and log‐PSA. For risk analysis, Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) and natural cubic Cox regression splines producing standardized cancer‐free probabilities were fitted. Results showed that baseline Serum PSA decreased by 1.6% (95% CI: ?2.1 to ?1.1) with every one unit increase in BMI. Statistically significant decreases of 3.7, 11.7 and 32.3% were seen for increasing BMI‐categories of 25 < 30, 30 < 35 and ≥35 kg/m², respectively, compared to the reference (18.5 < 25 kg/m²). No statistically significant associations were seen between BMI and prostate cancer risk although results were indicative of a positive association to incidence rates of high‐grade disease and an inverse association to incidence of low‐grade disease. However, findings regarding risk are limited by the short follow‐up time. In conclusion, BMI was inversely associated to PSA‐levels. BMI should be taken into consideration when referring men to a prostate biopsy based on serum PSA‐levels.     

Initial evaluation of PET/CT with 18F‐FSU‐880 targeting prostate‐specific membrane antigen in prostate cancer patients

This first‐in‐man study was carried out to evaluate the safety, whole‐body distribution, dose estimation, and lesion accumulation of ¹⁸F‐FSU‐880, a newly developed probe targeting prostate‐specific membrane antigen. Six prostate cancer patients with known metastatic lesions underwent serial whole‐body PET/computed tomography (CT) with ¹⁸F‐FSU‐880. Blood and urine were analyzed before and after PET/CT. Accumulation of ¹⁸F‐FSU‐880 in organs and metastatic lesions in serial PET images were evaluated by measuring the standardized uptake values. From the biodistribution data, the organ doses and whole‐body effective dose were calculated using OLINDA/EXM software was developed by Dr. Michael Stabin of Vanderbilt University, Nashville, Tennessee, USA. ¹⁸F‐FSU‐880 PET/CT could be carried out without significant adverse effects. High physiological uptake was observed in the salivary/lachrymal glands and kidneys. The effective dose was calculated to be 0.921 × 10^?2 mSv/MBq. Known metastatic lesions were clearly visualized with high image contrast that increased with time, except in 1 patient, whose bone metastases were well‐controlled and inactive. The PET/CT with ¹⁸F‐FSU‐880 could be carried out safely and could clearly visualize active metastatic lesions. The present results warrant further clinical studies with a larger number of cases to verify the clinical utility of ¹⁸F‐FSU‐880 PET/CT in the management of prostate cancer patients.     

18F‐fluorodeoxyglucose positron emission tomography imaging in brain tumours: The Western Australia positron emission tomography/cyclotron service experience

¹⁸F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) scans in the first 49 patients referred with either possible brain tumour or brain tumour recurrence were reviewed. FDG‐PET imaging was reported with reference to anatomical imaging. Based on the report the FDG study was classified as either positive or negative for the presence of tumour. Thirty‐eight cases were included in the analysis, 21 having pathological data and 17 with diagnostic clinical follow up. Eleven were excluded, as they had inadequate follow‐up data. Of the 21 cases with pathology, 18 were shown to have tumour. In this group there were five false‐negative scans and two false‐positive PET scans. Seventeen cases were assessed by clinical follow up, nine were considered to have been tumour. There were two false negatives with one false positive. The overall sensitivity, specificity and positive and negative predictive values were 74, 73, 87 and 53% respectively. This is similar to figures previously quoted in published work. Despite relatively limited numbers, the utility of FDG PET imaging in our hands is similar to published reports. With a positive predictive value of 87%, a positive FDG study indicates a high likelihood that there is brain tumour present. A negative study does not exclude the presence of tumour.     

Impact of recent screening on predicting the outcome of prostate cancer biopsy in men with elevated prostate‐specific antigen

BACKGROUND:

Risk models to predict prostate cancer on biopsy, whether they include only prostate‐specific antigen (PSA) or other markers, are intended for use in all men of screening age. However, the association between PSA and cancer probably depends on a man's recent screening history.

METHODS:

The authors examined the effect of prior screening on the ability to predict the risk of prostate cancer by using a previously reported, 4‐kallikrein panel that included total PSA, free PSA, intact PSA, and human kallikrein‐related peptidase 2 (hK2). The study cohort comprised 1241 men in Gothenburg, Sweden who underwent biopsy for elevated PSA during their second or later visit for the European Randomized Study of Screening for Prostate Cancer. The predictive accuracy of the 4‐kallikrein panel was calculated.

RESULTS:

Total PSA was not predictive of prostate cancer. The previously published 4‐kallikrein model increased predictive accuracy compared with total PSA and age alone (area under the curve [AUC], 0.66 vs 0.51; P < .001) but was poorly calibrated and missed many cancers. A model that was developed with recently screened men provided important improvements in discrimination (AUC, 0.67 vs 0.56; P < .001). Using this model reduced the number of biopsies by 413 per 1000 men with elevated PSA, missed 60 of 216 low‐grade cancers (Gleason score ≤6), but missed only 1 of 43 high‐grade cancers.

CONCLUSIONS:

Previous participation in PSA screening dramatically changed the performance of statistical models that were designed to predict biopsy outcome. A 4‐kallikrein panel was able to predict prostate cancer in men who had a recent screening history and provided independent confirmation that multiple kallikrein forms contribute important diagnostic information for men with elevated PSA. Cancer 2010. © 2010 American Cancer Society.     

Variation in general practice prostate‐specific antigen testing and prostate cancer outcomes: An ecological study

Knowledge is sparse about the consequences of variation in prostate‐specific antigen (PSA) testing rates in general practice. This study investigated associations between PSA testing and prostate cancer‐ related outcomes in Danish general practice, where screening for prostate cancer is not recommended. National registers were used to divide general practices into four groups based on their adjusted PSA test rate 2004–2009. We analysed associations between PSA test rate and prostate cancer‐related outcomes using Poisson regression adjusted for potential confounders. We included 368 general practices, 303,098 men and 4,199 incident prostate cancers. Men in the highest testing quartile of practices compared to men in the lowest quartile had increased risk of trans‐rectal ultrasound (incidence rate ratio (IRR): 1.20, 95% CI, 0.95–1.51), biopsy (IRR: 1.76, 95% CI, 1.54–2.02), and getting a prostate cancer diagnosis (IRR: 1.37, 95% CI, 1.23–1.52). More were diagnosed with local stage disease (IRR: 1.61, 95% CI, 1.37–1.89) with no differences regarding regional or distant stage. The IRR for prostatectomy was 2.25 (95% CI, 1.72–2.94) and 1.28 (95% CI, 1.02–1.62) for radiotherapy. No differences in prostate cancer or overall mortality were found between the groups. These results show that the highest PSA testing general practices may not reduce prostate cancer mortality but increase the downstream use of diagnostic and surgical procedures with potentially harmful side effects.     

Complete regression of bone metastases on super bone scan,by low-dose cisplatin,UFT, diethylstilbestrol diphosphate,and dexamethasone in a patient with hormone-refractory prostate cancer

Many types of chemotherapy are now being attempted all over the world for hormone-refractory prostate cancer (HRPC) patients, and prostate-specific antigen (PSA) reduction in almost half of the treated patients has been reported. However, only a few studies have reported the response of bone metastasis. The authors report a patient with HRPC who obtained complete regression of bone metastases on super bone scan by biochemical modulation (BM), dexamethasone, and endocrine therapy. Received: July 18, 2002 / Accepted: January 20, 2003 Correspondence to:S. Hoshi     

Tumor‐suppressive microRNA‐223 inhibits cancer cell migration and invasion by targeting ITGA3/ITGB1 signaling in prostate cancer

Analysis of microRNA (miRNA) expression signatures in prostate cancer (PCa) and castration‐resistant PCa has revealed that miRNA‐223 is significantly downregulated in cancer tissues, suggesting that miR‐223 acts as a tumor‐suppressive miRNA by targeting oncogenes. The aim of this study was to investigate the functional roles of miR‐223 and identify downstream oncogenic targets regulated by miR‐223 in PCa cells. Functional studies of miR‐223 were carried out to investigate cell proliferation, migration, and invasion using PC3 and PC3M PCa cell lines. Restoration of miR‐223 significantly inhibited cancer cell migration and invasion in PCa cells. In silico database and genome‐wide gene expression analyses revealed that ITGA3 and ITGB1 were direct targets of miR‐223 regulation. Knockdown of ITGA3 and ITGB1 significantly inhibited cancer cell migration and invasion in PCa cells by regulating downstream signaling. Moreover, overexpression of ITGA3 and ITGB1 was observed in PCa clinical specimens. Thus, our data indicated that downregulation of miR‐223 enhanced ITGA3/ITGB1 signaling and contributed to cancer cell migration and invasion in PCa cells. Elucidation of the molecular pathways modulated by tumor‐suppressive miRNAs provides insights into the mechanisms of PCa progression and metastasis.     

Time to prostate‐specific antigen nadir independently predicts overall survival in patients who have metastatic hormone‐sensitive prostate cancer treated with androgen‐deprivation therapy

BACKGROUND:

The objective of this study was to evaluate the relation between the kinetics of prostate‐specific antigen (PSA) decline after the initiation of androgen‐deprivation therapy (ADT) and overall survival (OS) in men with metastatic, hormone‐sensitive prostate cancer (HSPC).

METHODS:

The authors' institutional database was used to identify a cohort of men with metastatic HSPC who were treated with ADT. Patients were included if they had at least 2 serum PSA determinations before PSA nadir and at least 1 serum PSA value available within 1 month of ADT initiation. Patient characteristics, PSA at ADT initiation, nadir PSA, time to PSA nadir (TTN), and PSA decline (PSAD) in relation to OS were analyzed.

RESULTS:

One hundred seventy‐nine patients were identified, and they had a median follow‐up after ADT initiation of 4 years. The median OS after ADT initiation was 7 years. The median PSA level at ADT initiation and PSA nadir were 47 ng/mL and 0.28 ng/mL, respectively. On univariate analysis: TTN <6 months, PSAD >52 ng/mL per year, PSA nadir ≥0.2 ng/mL, PSA ≥47.2 ng/mL at ADT initiation, and Gleason score >7 were associated with shorter OS. On multivariate analysis, TTN <6 months, Gleason score >7, and PSA nadir ≥0.2 ng/mL independently predicted shorter OS.

CONCLUSIONS:

To the authors' knowledge, this was the first report to demonstrate that a faster time to reach a PSA nadir after the initiation of ADT was associated with shorter survival duration in men with metastatic HSPC. These results need confirmation but may indicate that a rapid initial response to ADT indicates more aggressive disease. Cancer 2009. © 2009 American Cancer Society.     

Prevalence of non 18F‐fluorodeoxyglucose‐avid incidental findings of clinical significance on whole body positron emission tomography/computed tomography: A review of 500 consecutive cases

Introduction

The prevalence of incidental ¹⁸F‐fluorodeoxyglucose (FDG)‐avid findings on positron emission tomography–computed tomography (PET/CT) has been extensively described. Few studies, however, have assessed the prevalence and significance of non‐FDG‐avid findings; pathology that is identified on review of the low‐dose, non‐contrast CT. The aim of this study was to determine the overall prevalence of non FDG‐avid incidental findings on PET/CT and the prevalence of ‘clinically significant’ non FDG‐avid pathology.

Methods

Five hundred consecutive whole body PET/CT studies performed in 2016 at a university affiliated tertiary hospital were retrospectively reviewed by two radiologists experienced in reporting PET/CT. Findings were categorized according to potential clinical relevance, and a targeted follow‐up of clinically significant incidental findings was performed.

Results

Incidental findings were encountered in 463 of 500 (92.6%) patients. In 226 patients, these findings had been detected on previous imaging studies, with unknown incidental findings present in 237 of 500 (47.4%) patients. 113 of 500 (22.6%) patients had non‐avid incidental findings of potentially major clinical significance, and in 35 patients (7.0%) these findings were considered previously unknown. The most common non‐avid findings of potentially major significance were pulmonary nodules (6 mm or larger), moderate or large size pleural effusions, and vascular aneurysms. Unknown incidental findings of potentially major clinical significance were significantly higher in patients imaged for melanoma staging (P= 0.004).

Conclusion

The prevalence of incidental findings of clinical significance that do not accumulate FDG in PET/CT is not insignificant. Routine systematic review of the low‐dose CT is required to avoid missing potentially clinically important findings, in particular pleural effusions, vascular aneurysms and metastatic pulmonary nodules.