Two Decades of Active Surveillance for Prostate Cancer in a Single-Center Cohort: Favorable Outcomes after Transurethral Resection of the Prostate

Objective: To report the outcomes of active surveillance (AS) for low-risk prostate cancer (PCa) in a single-center cohort. Patients and Methods: This is a prospective, single-center, observational study. The cohort included all patients who underwent AS for PCa between December 1999 and December 2020 at our institution. Follow-up appointments (FU) ended in February 2021. Results: A total of 413 men were enrolled in the study, and 391 had at least one FU. Of those who followed up, 267 had PCa diagnosed by transrectal ultrasound (TRUS)-guided biopsy (T1c: 68.3%), while 124 were diagnosed after transurethral resection of the prostate (TURP) (T1a/b: 31.7%). Median FU was 46 months (IQR 25–90). Cancer specific survival was 99.7% and overall survival was 92.3%. Median reclassification time was 11.2 years. After 20 years, 25% of patients were reclassified within 4.58 years, 6.6% opted to switch to watchful waiting, 4.1% died, 17.4% were lost to FU, and 46.8% remained on AS. Those diagnosed by TRUS had a significantly higher reclassification rate than those diagnosed by TURP (p < 0.0001). Men diagnosed by targeted MRI/TRUS fusion biopsy tended to have a higher reclassification probability than those diagnosed by conventional template biopsies (p = 0.083). Conclusions: Our single-center cohort spanning over two decades revealed that AS remains a safe option for low-risk PCa even in the long term. Approximately half of AS enrollees will eventually require definitive treatment due to disease progression. Men with incidental prostate cancer were significantly less likely to have disease progression.

Folic Acid-Decorated β-Cyclodextrin-Based Poly(ε-caprolactone)-dextran Star Polymer with Disulfide Bond-Linker as Theranostic Nanoparticle for Tumor-Targeted MRI and Chemotherapy

β-cyclodextrin(βCD)-based star polymers have attracted much interest because of their unique structures and potential biomedical and biological applications. Herein, a well-defined folic acid (FA)-conjugated and disulfide bond-linked star polymer ((FA-Dex-SS)-βCD-(PCL)14) was synthesized via a couple reaction between βCD-based 14 arms poly(ε-caprolactone) (βCD-(PCL)14) and disulfide-containing α-alkyne dextran (alkyne-SS-Dex), and acted as theranostic nanoparticles for tumor-targeted MRI and chemotherapy. Theranostic nanoparticles were obtained by loading doxorubicin (DOX), and superparamagnetic iron oxide (SPIO) particles were loaded into the star polymer nanoparticles to obtain ((FA-Dex-SS)-βCD-(PCL)14@DOX-SPIO) theranostic nanoparticles. In vitro drug release studies showed that approximately 100% of the DOX was released from disulfide bond-linked theranostic nanoparticles within 24 h under a reducing environment in the presence of 10.0 mM GSH. DOX and SPIO could be delivered into HepG2 cells efficiently, owing to the folate receptor-mediated endocytosis process of the nanoparticles and glutathione (GSH), which triggered disulfide-bonds cleaving. Moreover, (FA-Dex-SS)-βCD-(PCL)14@DOX-SPIO showed strong MRI contrast enhancement properties. In conclusion, folic acid-decorated reduction-sensitive star polymeric nanoparticles are a potential theranostic nanoparticle candidate for tumor-targeted MRI and chemotherapy.

Active surveillance inclusion criteria under scrutiny in magnetic resonance imaging-guided prostate biopsy: a multicenter cohort study

Background Although multiparametric magnetic resonance imaging (mpMRI) is recommended for primary risk stratification and follow-up in Active Surveillance (AS), it is not part of common AS inclusion criteria. The objective was to compare AS eligibility by systematic biopsy (SB) and combined MRI-targeted (MRI-TB) and SB within real-world data using current AS guidelines. Methods A retrospective multicenter study was conducted by a German prostate cancer (PCa) working group representing six tertiary referral centers and one outpatient practice. Men with PCa and at least one MRI-visible lesion according to Prostate Imaging Reporting and Data System (PI-RADS) v2 were included. Twenty different AS inclusion criteria of international guidelines were applied to calculate AS eligibility using either a SB or a combined MRI-TB and SB. Reasons for AS exclusion were assessed. Results Of 1941 patients with PCa, per guideline, 583–1112 patients with PCa in both MRI-TB and SB were available for analysis. Using SB, a median of 22.1% (range 6.4–72.4%) were eligible for AS. Using the combined approach, a median of 15% (range 1.7–68.3%) were eligible for AS. Addition of MRI-TB led to a 32.1% reduction of suitable patients. Besides Gleason Score upgrading, the maximum number of positive cores were the most frequent exclusion criterion. Variability in MRI and biopsy protocols potentially limit the results. Conclusions Only a moderate number of patients with PCa can be monitored by AS to defer active treatment using current guidelines for inclusion in a real-world setting. By an additional MRI-TB, this number is markedly reduced. These results underline the need for a contemporary adjustment of AS inclusion criteria.

MRI as a Tool to Assess Interstitial Cystitis Associated Bladder and Brain Pathologies

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic, often incapacitating condition characterized by pain seeming to originate in the bladder in conjunction with lower urinary tract symptoms of frequency and urgency, and consists of a wide range of clinical phenotypes with diverse etiologies. There are currently no diagnostic tests for IC/BPS. Magnetic resonance imaging (MRI) is a relatively new tool to assess IC/BPS. There are several methodologies that can be applied to assess either bladder wall or brain-associated alterations in tissue morphology and/or pain. IC/BPS is commonly associated with bladder wall hyperpermeability (BWH), particularly in severe cases. Our group developed a contrast-enhanced magnetic resonance imaging (CE-MRI) approach to assess BWH in preclinical models for IC/BPS, as well as for a pilot study for IC/BPS patients. We have also used the CE-MRI approach to assess possible therapies to alleviate the BWH in preclinical models for IC/BPS, which will hopefully pave the way for future clinical trials. In addition, we have used molecular-targeted MRI (mt-MRI) to quantitatively assess BWH biomarkers. Biomarkers, such as claudin-2, may be important to assess and determine the severity of BWH, as well as to assess therapeutic efficacy. Others have also used other MRI approaches to assess the bladder wall structural alterations with diffusion-weighted imaging (DWI), by measuring changes in the apparent diffusion coefficient (ADC), diffusion tensor imaging (DTI), as well as using functional MRI (fMRI) to assess pain and morphological MRI or DWI to assess anatomical or structural changes in the brains of patients with IC/BPS. It would be beneficial if MRI-based diagnostic tests could be routinely used for these patients and possibly used to assess potential therapeutics.

A Type I Collagen-Targeted MR Imaging Probe for Staging Fibrosis in Crohn’s Disease

Fibrostenosis is a serious complication of Crohn’s disease (CD), affecting approximately one-half of all patients. Surgical resection is the typical clinical end due to ineffective antifibrotic therapy mainly through anti-inflammatory treatment and fibrosis can be reverted only at early stages. Mover, human fibrotic disorders is known to be associated with aging process. Thus, accurate monitoring of the progression of fibrosis is crucial for CD management as well as can be benefit to aging related fibrosis. The excessive deposition of type I collagen (ColI) is the core point in major complications of fibrosis, including that in patients with CD and aging related fibrosis. Therefore, a MR imaging probe (EP-3533) targeted ColI was employed to stage bowel fibrosis in CD using a rat model and to compare its efficiency with the common MR imaging contrast medium gadopentetatedimeglumine (Gd-DTPA). The bowel fibrotic rat model was established with different degrees of bowel fibrosis, were scanned using a 3.0-T MRI scanner with a specialized animal coil. MRI sequence including T1 mapping and T1-weighed imaging were performed before and after injecting the MRI probe (EP-3533 or Gd-DTPA). The T1 relaxation time (T1 value) and change in the contrast-to-noise ratio (ΔCNR) were measured to evaluate bowel fibrosis. Masson’s trichrome staining was performed to determine the severity of fibrosis. EP-3533 offered a better longitudinal relaxivity (r1) with 67.537 L/mmol·s, which was approximately 13 times that of Gd-DTPA. The T1 value on bowel segments was reduced in the images from EP-3533 compared to that from Gd-DTPA (F = 16.478; p &lt; 0.001). Additionally, a better correlation between ΔCNR calculated from EP-3533 imaging and bowel fibrosis (AUC = 0.846) was determined 10 min after enhanced media administration than with Gd-DTPA (AUC = 0.532). The 10th-minute ΔCNR performed using the ColI probe showed the best correlation with the severity of bowel fibrosis (r = 0.538; p = 0.021). Our results demonstrates that targeted MRI probe (EP-3533) supplies a better enhanced effect compared to Gd-DTPA and could be a promising method to evaluate the progression and monitor the therapeutic response of bowel fibrosis.

Folic Acid Decorated β-Cyclodextrin-Based Poly(ε-Caprolactone)/Dextran Star Polymer with Disulfide Bond-Linker as Theranostic Nanoparticle for Tumor-Targeted MRI and Chemotherapy

&beta;-cyclodextrin-based star polymers have attracted much interest because of their unique structures and potential biomedical and biological applications. Herein, we synthesized well-defined folic acid (FA)-conjugated and disulfide bond-linked star polymer ((FA-Dex-SS)-&beta;CD-(PCL)14) acted as theranostic nanoparticles for tumor-targeted magnetic resonance imaging (MRI) and chemotherapy. Theranostic nanoparticles were obtained by loading doxorubicin (DOX) and superparamagnetic iron oxide particles (SPIO) were loaded into the star polymer nanoparticles to obtain ((FA-Dex-SS)-&beta;CD-(PCL)14@DOX/SPIO) theranostic nanoparticles. In vitro drug release studies showed that approximately 100% of the DOX was released from disulfide bond-linked theranostic nanoparticles within 24 h under a reducing environment in the presence of 10.0 mM GSH. DOX and SPIO could be delivered into HepG2 cells efficiently, owing to folate receptor-mediated endocytosis process of the nanoparticles and GSH triggered disulfide-bonds cleaving.Moreover, (FA-Dex-SS)-&beta;CD-(PCL)14@DOX/SPIO showed strong MRI contrast enhancement properties. In conclusion, folate-decorated reduction-sensitive star polymeric nanoparticles are a potential theranostic nanoparticle candidate for tumor-targeted MRI and chemotherapy.