Focal therapy for prostate cancer: Recent advances and future directions

© 2020, Millennium Medical Publishing, Inc. All rights reserved. Prostate cancer is the most frequently diagnosed cancer in men after skin cancer. Owing to the rising popularity of prostate-specific antigen screening, large numbers of patients are receiving a diagnosis of prostate cancer and undergoing whole-gland treatment. Some patients with a diagnosis of low-risk, localized disease may not benefit from whole-gland treatment, however, given its known morbidity. In response to advances in prostate imaging and evidence suggesting that the prognosis in prostate cancer is related to the index lesion, many patients have begun to opt for focal therapy, which targets a lesion rather than the entire prostate. This “middle ground” of therapy, between active surveillance and whole-gland treatment, is appealing to patients because the risk for side effects is believed to be lower with focal therapy than with whole-gland treatment. This review discusses the oncologic rationale for focal therapy in localized prostate cancer, examines the major therapy modalities, and addresses future directions

Quantitative Characterization of the Prostatic Urethra Using MRI: Implications for Lower Urinary Tract Symptoms in Patients with Benign Prostatic Hyperplasia

© 2020 Introduction: The aim of this study was to perform a quantitative assessment of the prostate anatomy with a focus on the relation of prostatic urethral anatomic variation to urinary symptoms. Methods: This retrospective study involved patients undergoing magnetic resonance imaging for prostate cancer who were also assessed for lower urinary tract symptoms. Volumetric segmentations were utilized to derive the in vivo prostatic urethral length and urethral trajectory in coronal and sagittal planes using a piece-wise cubic spline function to derive the angle of the urethra within the prostate. Association of anatomical factors with urinary symptoms was evaluated using ordinal univariable and multivariable logistic regression with IPSS score cutoffs of ≤7, 8–19, and \u3e20 to define mild, moderate, and severe symptoms, respectively. Results: A total of 423 patients were included. On univariable analysis, whole prostate volume, transition zone volume, prostatic urethral length, urethral angle, and retrourethral volume were all significantly associated with worse urinary symptoms. On multivariable analysis prostatic urethral length was associated with urinary symptoms with a normalized odds ratio of 1.5 (95% confidence interval 1.0–2.2, p = 0.04). In a subset analysis of patients on alpha blockers, maximal urethral angle, transition zone volume as well as urethral length were all associated with worse urinary symptoms. Conclusion: Multiple parameters were associated with worse urinary symptoms on univariable analysis, but only prostatic urethral length was associated with worse urinary symptoms on multivariable analysis. This study demonstrates the ability of quantitative assessment of prostatic urethral anatomy to predict lower urinary tract symptoms

Preoperative Renal Parenchyma Volume as a Predictor of Kidney Function Following Nephrectomy of Complex Renal Masses

Background: The von Hippel-Lindau disease (VHL) is a hereditary cancer syndrome with multifocal, bilateral cysts and solid tumors of the kidney. Surgical management may include multiple extirpative surgeries, which ultimately results in parenchymal volume loss and subsequent renal function decline. Recent studies have utilized parenchyma volume as an estimate of renal function prior to surgery for renal cell carcinoma; however, it is not yet validated for surgically altered kidneys with multifocal masses and complex cysts such as are present in VHL. Objective: We sought to validate a magnetic resonance imaging (MRI)-based volumetric analysis with mercaptoacetyltriglycine (MAG-3) renogram and postoperative renal function. Design, setting, and participants: We identified patients undergoing renal surgery at the National Cancer Institute from 2015 to 2020 with preoperative MRI. Renal tumors, cysts, and parenchyma of the operated kidney were segmented manually using ITK-SNAP software. Outcome measurements and statistical analysis: Serum creatinine and urinalysis were assessed preoperatively, and at 3- and 12-mo follow-up time points. Estimated glomerular filtration rate (eGFR) was calculated using serum creatinine-based CKD-EPI 2021 equation. A statistical analysis was conducted on R Studio version 4.1.1. Results and limitations: Preoperative MRI scans of 113 VHL patients (56% male, median age 48 yr) were evaluated between 2015 and 2021. Twelve (10.6%) patients had a solitary kidney at the time of surgery; 59 (52%) patients had at least one previous partial nephrectomy on the renal unit. Patients had a median of three (interquartile range [IQR]: 2–5) tumors and five (IQR: 0–13) cysts per kidney on imaging. The median preoperative GFR was 70 ml/min/1.73 m2 (IQR: 58–89). Preoperative split renal function derived from MAG-3 studies and MRI split renal volume were significantly correlated (r = 0.848, p < 0.001). On the multivariable analysis, total preoperative parenchymal volume, solitary kidney, and preoperative eGFR were significant independent predictors of 12-mo eGFR. When only considering patients with two kidneys undergoing partial nephrectomy, preoperative parenchymal volume and eGFR remained significant predictors of 12-mo eGFR. Conclusions: A parenchyma volume analysis on preoperative MRI correlates well with renogram split function and can predict long-term renal function with added benefit of anatomic detail and ease of application. Patient summary: Prior to kidney surgery, it is important to understand the contribution of each kidney to overall kidney function. Nuclear medicine scans are currently used to measure split kidney function. We demonstrated that kidney volumes on preoperative magnetic resonance imaging can also be used to estimate split kidney function before surgery, while also providing essential details of tumor and kidney anatomy

Association of CDH1 Germline Variants and Colon Polyp Phenotypes in Patients With Hereditary Diffuse Gastric Cancer

Background and Aims: Germline CDH1 variants resulting in E-cadherin loss of function result in an increased risk of diffuse type gastric cancer and lobular type breast cancer. However, the risk of developing other epithelial neoplasms, specifically colorectal cancer, is unknown. Methods: Patients enrolled in a prospective natural history study of hereditary gastric cancer who underwent at least one colonoscopy were evaluated. Results: Of 300 patients with CDH1 pathogenic or likely pathogenic variants, 85 underwent colonoscopy. More than half of patients (56%, 48/85) had at least one colorectal polyp. Most of those patients (83%, 40/48) had at least one precancerous polyp (adenoma or sessile serrated lesion). More than half (56%) of patients aged less than 45 years had a colorectal polyp. Of those with polyps, the most frequent CDH1 variant type was canonical splice site (27%, 13/48) followed by nonsense (21%, 10/48). There was no association between CDH1 variant type and increased likelihood of colorectal polyps. Conclusion: In summary, a majority of CDH1 variant carriers who underwent colonoscopy had colorectal polyps detected and most subjects were aged less than 45 years. This study of colorectal cancer risk based on the prevalence of colorectal polyps in the CDH1 population requires further investigation to appropriately counsel patients on colorectal cancer screening. Clinical trial registry website: https://clinicaltrials.gov/. Clinical trial number: NCT03030404

Combined MRI-targeted Plus Systematic Confirmatory Biopsy Improves Risk Stratification for Patients Enrolling on Active Surveillance for Prostate Cancer

© 2020 Elsevier Inc. Objective: To evaluate the efficacy of combined MRI-targeted plus systematic 12-core biopsy (Cbx) to aid in the selection of patients for active surveillance (AS). Methods: From July 2007 to January 2020, patients with Gleason Grade Group (GG) 1 or GG 2 prostate cancer were referred to our center for AS consideration. All patients underwent an MRI and confirmatory combined MRI-targeted plus systematic biopsy (Cbx), and AS outcomes based on Cbx results were compared. Cox regression was used to identify predictors of AS failure, defined as progression to ≥ GG3 disease on follow-up biopsies. Results: Of 579 patients referred for AS, 79.3% (459/579) and 20.7% (120/579) had an initial diagnosis of GG1 and GG2 disease, respectively. Overall, 43.2% of patients (250/579) were upgraded on confirmatory Cbx, with 19.2% (111/579) upgraded to ≥ GG3. For the 226 patients followed on AS, 32.7% (74/226) had benign, 45.6% (103/226) had GG1, and 21.7% (49/226) had GG2 results on confirmatory Cbx. In total, 28.8% (65/226) of patients eventually progressed to ≥ GG3, with a median time to AS failure of 89 months. The median time from confirmatory Cbx to AS failure for the negative, GG1, and GG2 groups were 97, 97, and 32 months, respectively (p \u3c.001). On multivariable regression, only age (hazard ratio 1.06 [1.02-1.11], p \u3c.005) and GG on confirmatory Cbx (hazard ratio 2.75 [1.78-4.26], p \u3c.005) remained as positive predictors of AS failure. Conclusion: The confirmatory combined MRI-targeted plus systematic biopsy provides useful information for the risk stratification of patients at the time of AS enrollment

MRI-targeted, systematic, and combined biopsy for prostate cancer diagnosis

Copyright © 2020 Massachusetts Medical Society. BACKGROUND The use of 12-core systematic prostate biopsy is associated with diagnostic inaccuracy that contributes to both overdiagnosis and underdiagnosis of prostate cancer. Biopsies performed with magnetic resonance imaging (MRI) targeting may reduce the misclassification of prostate cancer in men with MRI-visible lesions. METHODS Men with MRI-visible prostate lesions underwent both MRI-targeted and systematic biopsy. The primary outcome was cancer detection according to grade group (i.e., a clustering of Gleason grades). Grade group 1 refers to clinically insignificant disease; grade group 2 or higher, cancer with favorable intermediate risk or worse; and grade group 3 or higher, cancer with unfavorable intermediate risk or worse. Among the men who underwent subsequent radical prostatectomy, upgrading and downgrading of grade group from biopsy to whole-mount histopathological analysis of surgical specimens were recorded. Secondary outcomes were the detection of cancers of grade group 2 or higher and grade group 3 or higher, cancer detection stratified by previous biopsy status, and grade reclassification between biopsy and radical prostatectomy. RESULTS A total of 2103 men underwent both biopsy methods; cancer was diagnosed in 1312 (62.4%) by a combination of the two methods (combined biopsy), and 404 (19.2%) underwent radical prostatectomy. Cancer detection rates on MRI-targeted biopsy were significantly lower than on systematic biopsy for grade group 1 cancers and significantly higher for grade groups 3 through 5 (P\u3c0.01 for all comparisons). Combined biopsy led to cancer diagnoses in 208 more men (9.9%) than with either method alone and to upgrading to a higher grade group in 458 men (21.8%). However, if only MRI-target biopsies had been performed, 8.8% of clinically significant cancers (grade group ≥3) would have been misclassified. Among the 404 men who underwent subsequent radical prostatectomy, combined biopsy was associated with the fewest upgrades to grade group 3 or higher on histopathological analysis of surgical specimens (3.5%), as compared with MRI-targeted biopsy (8.7%) and systematic biopsy (16.8%). CONCLUSIONS Among patients with MRI-visible lesions, combined biopsy led to more detection of all prostate cancers. However, MRI-targeted biopsy alone underestimated the histologic grade of some tumors. After radical prostatectomy, upgrades to grade group 3 or higher on histopathological analysis were substantially lower after combined biopsy. (Funded by the National Institutes of Health and others; Trio Study ClinicalTrials.gov number, NCT00102544.)