•Dynamic signal changes are seen on MRI after focal cryotherapy for prostate cancer.•Most lesions show hyperintensity at 3 months post-treatment on T2WI, T1WI, and DWI.•All lesions show hypointensity ...after 17 months on T2WI, T1WI, and DWI.•Peripheral enhancement is often observed and disappears after 23 months on DCE-MRI.•Transient internal enhancement may be observed in the early post-treatment period.
To evaluate the time-course changes of multiparametric MRI findings following focal cryotherapy for localized prostate cancer.
Sixteen patients who underwent focal cryotherapy as an initial curative treatment for localized prostate cancer during March 2017–April 2021 were included. Before the treatment, the patients underwent targeted prostate biopsy using MRI–transrectal ultrasound fusion. Overall, 64 MRIs were conducted after focal cryotherapy and the temporal post-treatment MR signal changes of the ablated area in T2WI, T1WI, DWI, and DCE-MRI were analyzed.
Technical success was achieved in all patients. The median follow-up period was 22 months. The initial post-treatment MRI revealed significant signal changes in the target lesions for all patients, including the disappearance of findings suggestive of cancer. At 3 months post-treatment, most lesions were hyperintense with a hypointense rim on T2WI, T1WI, and DWI (83.3 %). After 6 months, hyperintensity reduced, and after 17 months, all lesions showed hypointensity in these sequences. DCE-MRI of most patients showed loss of internal enhancement; however, one patient exhibited residual nodular enhancement in the ablated area at 3 months, which disappeared after 6 months. Peripheral enhancement was common at 3 months, disappearing after 23 months. Two patients showed biopsy-evidenced local recurrence. The recurrent lesions showed hypointensity on T2WI with diffusion restriction and early contrast enhancement in the ventral transition zone.
MRI findings of the ablated sites following focal cryotherapy for localized prostate cancer show dynamic signal changes, especially within the first 6 months.
Intraductal carcinoma of the prostate is a marker of aggressive disease. However, intraductal carcinoma exists on a morphologic continuum with high-grade prostatic intraepithelial neoplasia (PIN) and ...distinguishing intraductal carcinoma from PIN is a common diagnostic dilemma with significant clinical implications. We evaluated whether immunostains for PTEN and ERG can sensitively identify intraductal carcinoma and accurately distinguish it from high-grade PIN. A combined immunostain for PTEN, ERG, p63 and CK903 was developed and validated. Radical prostatectomy specimens with lesions meeting criteria for intraductal carcinoma (n=45), intraductal cribriform proliferations falling short of intraductal carcinoma (n=15), and PIN lesions (n=39) were retrospectively identified and assessed for PTEN and ERG. Cytoplasmic PTEN loss was identified in 84% (38/45) of the intraductal carcinoma and 100% (15/15) of intraductal cribriform proliferation cases. In contrast, cytoplasmic PTEN loss was never observed in PIN (0/39; P<0.0001). Of the 53 cases of intraductal carcinoma or intraductal cribriform proliferation with cytoplasmic PTEN loss, it was homogeneously lost in 42 cases (79%). Weak, focal nuclear positivity for PTEN was retained in 31 of these 42 cases (74%). ERG expression was identified in 58% (26/45) of intraductal carcinoma and 67% (10/15) of intraductal cribriform proliferations compared with 13% (5/39) of PIN. Concordance between the PTEN/ERG status of the intraductal carcinoma lesions and the concurrent invasive carcinoma was high (>95% and P<0.0001 for each), and substantially less for PIN and the concurrent invasive tumor (83% for PTEN and 67% for ERG; P=NS for each). Cytoplasmic PTEN loss occurs in the majority of intraductal carcinoma and intraductal cribriform proliferation cases. Cytoplasmic PTEN loss was never observed in PIN (100% specificity). Our study identifies PTEN loss as a potentially useful marker to distinguish intraductal carcinoma from PIN and provides a plausible molecular explanation for why intraductal carcinoma is associated with poor prognosis.
Purpose
To examine phosphodiesterase type 5 (PDE5) expression in the anterior fibromuscular stroma (AFMS) of the prostate. Although PDE5 expression was identified in the human prostate, differences ...in PDE5 expression in intra-prostatic regions are unknown. The AFMS in the prostate has peculiar innervations that could contribute to voiding function. Here, we examined regional differences in PDE5 expression in the prostate with special reference to the AFMS.
Methods
A total 18 human prostate and bladder specimens were obtained. Tissue specimens were processed by hematoxylin–eosin (H&E) staining and immunohistochemistry for PDE5. Immunoreactivity with PDE5 was evaluated using computer-assisted image analysis in the following regions: the AFMS, bladder neck, stromal hyperplasia in the transition zone, glandular hyperplasia in the transition zone (TZ gland), and the peripheral zone (PZ). The correlation between PDE5 expression in the AFMS and clinical data was analysed.
Results
Image analysis revealed that the median ratio of the PDE5-immunoreactive area to smooth muscle area by H&E staining was 74.7% in the AFMS. There was significantly higher PDE5 expression in the AFMS than in the TZ gland (
p
= 0.034) and PZ (
p
= 0.002). PDE5 expression in the AFMS was not significantly correlated with age, prostate volume, transition zone volume, or transition zone index. However, older men had a tendency to have higher PDE5 expression in the AFMS.
Conclusions
We found higher PDE5 expression in the AFMS compared with other prostatic regions, which suggested that the AFMS is a target region of PDE5 inhibitors in the prostate.
The MYC onco-protein is a transcription factor that regulates cell proliferation, metabolism, protein synthesis, mitochondrial function and stem cell renewal. A region on chromosome 8q24 encompassing ...the MYC locus is amplified in prostate cancer, but this occurs mostly in advanced disease suggesting that MYC alterations occur late in prostate cancer. In contrast, MYC mRNA is elevated in most prostate cancers, even those of relatively low stage and grade (eg Gleason score 6) suggesting that MYC plays a role in initiation. However, since MYC protein levels are tightly regulated, elevated MYC mRNA does not necessarily imply elevated MYC protein. Thus, it is critical to determine whether MYC protein is elevated in human prostate cancer, and if so, at what stage of the disease this elevation occurs. Prior studies of MYC protein localization have been hampered by lack of suitable antibodies and controls. We utilized a new anti-MYC antibody coupled with genetically defined control experiments to localize MYC protein within human tissue microarrays consisting of normal, atrophy, PIN, primary adenocarcinoma, and metastatic adenocarcinoma. Nuclear overexpression of MYC protein occurred frequently in luminal cells of PIN, as well as in most primary carcinomas and metastatic disease. MYC protein did not correlate with gain of 8q24, suggesting alternative mechanisms for MYC overexpression. These results provide evidence that upregulation of nuclear MYC protein expression is a highly prevalent and early change in prostate cancer and suggest that increased nuclear MYC may be a critical oncogenic event driving human prostate cancer initiation and progression.
Purpose
To assess the feasibility, safety, and outcomes of an expedited One-Stop prostate cancer (PCa) diagnostic pathway.
Patients and methods
We identified 370 consecutive patients who underwent ...multiparametric magnetic resonance imaging (mpMRI) and transrectal ultrasound fusion prostate biopsy (MRI/TRUS-PBx) from our institutional review board-approved database. Patients were divided according to diagnostic pathway: One-Stop (
n
= 74), with mpMRI and same-day PBx, or Standard (
n
= 296), with mpMRI followed by a second visit for PBx. mpMRIs were performed and interpreted according to Prostate Imaging-Reporting and Data System (PI-RADS v2). Grade group ≥ 2 PCa defined clinically significant PCa (csPCa). Statistical significance was considered when
p
< 0.05.
Results
Age (66 vs 66 years,
p
= 0.59) and PSA density (0.1 vs 0.1 ng/mL
2
,
p
= 0.26) were not different between One-Stop vs Standard pathway, respectively. One-Stop patients lived further away from the hospital than Standard patients (163 vs 31 km;
p
< 0.01), and experienced shorter time from mpMRI to PBx (0 vs 7 days;
p
< 0.01). The number (
p
= 0.56) and distribution of PI-RADS lesions (
p
= 0.67) were not different between the groups. All procedures were completed successfully with similar perioperative complications rate (
p
= 0.24). For patients with PI-RADS 3–5 lesions, the csPCa detection rate (49% vs 41%,
p
= 0.55) was similar for One-Stop vs Standard, respectively. The negative predictive value of mpMRI (PI-RADS 1–2) for csPCa was 78% for One-Stop vs 83% for Standard (
p
= 0.99). On multivariate analysis, age, prostate volume and PI-RADS score (
p
< 0.01), but not diagnostic pathway, predicted csPCa detection.
Conclusion
A One-Stop PCa diagnostic pathway is feasible, safe, and provides similar outcomes in a shorter time compared to the Standard two-visit diagnostic pathway.
Purpose
To determine whether multi-parametric magnetic resonance imaging (mpMRI) can reliably predict proximity of prostate cancer to the prostatic urethra in a contemporary series of men undergoing ...radical prostatectomy (RP) at two academic centers.
Methods
Clinical characteristics of consecutive men undergoing pre-operative mpMRI prior to RP and whole-mount axial serial step-sectioned pathology examination at two academic centers between Jun 2016 and Oct 2018 were analyzed retrospectively. Every tumor was characterized by its pathologic minimum distance to the prostatic urethral lumen (pMDUL). Only the cancer closest to the urethra represented the prostatic urethral index lesion. The radiologic minimum distance of the index lesion to the prostatic urethral lumen was measured and noted as ≤ 5 mm versus > 5 mm. The sensitivity, specificity, positive and negative predicting values (PPV and NPV) and area under the receivers operating characteristics curve (AUC) were calculated for performance of mpMRI for predicting pMDUL ≤ 5 mm.
Results
Of the 163 surgical specimens examined, 112 (69%) exhibited a pMDUL ≤ 5 mm. These men had significantly higher grade group (GG) and advanced pathological and clinical stage. The rates of high PI-RADS score and presence of gross extracapsular extension were also significantly greater for the group with pMDUL ≤ 5 mm. The AUC, sensitivity, specificity, PPV, and NPV were 0.641, 51.8, 76.5, 82.9, and 42.4%, respectively, for mpMRI to predict pMDUL < 5 mm.
Conclusions
Nearly 70% of men undergoing RP present with tumor within 5 mm of the prostatic urethra. These tumors present higher risk characteristics, and mpMRI exhibited moderate performance and high PPV in their pre-operative detection. Physicians performing partial gland ablation should take these results into consideration during treatment selection and planning.
Objectives
To evaluate the impact of 5-alpha reductase inhibitors (5-ARIs) on definitive treatment (DT) and pathological progression (PP) in patients on active surveillance (AS) for prostate cancer.
...Methods
We identified 361 consecutive patients, from an IRB-approved database, on AS for prostate cancer with minimum 2 years follow-up. Patients were grouped into two cohorts, those using 5-ARIs (
5-ARI
;
n
= 119) or not using 5-ARIs (
no 5-ARI
;
n
= 242). Primary and secondary endpoints were treatment-free survival (TFS) and PP-free survival (PPFS), which were evaluated by Kaplan–Meier analysis. Univariate and multivariable cox regression analysis were used to identify predictors for PP and DT. A
p
value < 0.05 was considered statistically significant.
Results
Baseline characteristics and the prostate biopsy rate were similar between the two groups. Median (range) follow-up was 5.7 (2.0–17.2) years. Five-year and 10-year TFS was 92% and 59% for the
5-ARI
group versus 80% and 51% for the
no 5-ARI
group (
p
= 0.005), respectively. Five-year and 10-year PPFS was 77% and 41% for the
5-ARI
group versus 70% and 32% for the
no 5-ARI
group (
p
= 0.04), respectively. Independent predictors for treatment and PP were not taking 5-ARIs (
p
= 0.005;
p
= 0.02), entry PSA > 2.5 ng/mL (
p
= 0.03;
p
= 0.01) and Gleason pattern 4 on initial biopsy (
p
< 0.001;
p
< 0.001), respectively. The main limitation is the retrospective study design.
Conclusions
5-ARIs reduces reclassification and cross-over to treatment in men on active surveillance for prostate cancer. Further, taking 5-ARIs was an independent predictor for prostate cancer progression and definitive treatment.
Background
In all the prefectures of Japan, with the exception of Shiga Prefecture, more than half of local governments have an organized prostate‐specific antigen (PSA) screening system in place. ...However, in the Shiga Prefecture, only a single city performed PSA screening over the time period of this survey. The purpose of the present study was to determine the clinical, pathological, and therapeutic features of newly diagnosed prostate cancer in localities where a formally organized screening system was almost entirely absent.
Methods
A multicenter observational study was conducted in the Shiga Prefecture, which has the lowest rate of population‐based PSA‐screening in Japan. Patients' age, initial PSA, reasons for PSA testing, Gleason score, clinical stage, and primary treatments were surveyed. We stratified patients according to the reasons for PSA measurement, and compared the differences between groups subject to organized versus opportunistic screening.
Results
In the 2 years 2012 and 2017, 984 newly diagnosed prostate cancer patients were analyzed. Of these, 954 (97%) were opportunistically tested (i.e., not as part of an organized screening system), with the remaining 29 (3%) measured as part of an organized screening program. Patients in the former group exhibited a higher initial PSA value than in the organized screening group (median: 11.49 vs. 5.67 ng/ml). They also had worse clinical features, including higher Gleason score and TNM stage. More patients in the organized screening group were treated curatively than in the nonorganized screening group in terms of the primary treatment. The results were similar in a subanalysis of the patients of age 50–69 years.
Conclusions
Organized PSA screening contributes to increasing the number of patients diagnosed with early‐stage cancer who can be treated curatively.
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