Faculty Bibliography

OBJECTIVE:Early-stage prostate cancer may be followed with active surveillance to avoid overtreatment. Our institution's active surveillance regimen uses annual MRI in place of serial biopsies, and biopsies are performed only when clinically necessary. The objective of our study was to report the multiparametric MRI characteristics of prostate cancer patients who discontinued active surveillance at our institution after repeat imaging revealed possible evidence of tumor upgrading. MATERIALS AND METHODS/METHODS:The Department of Urology at Winthrop University Hospital prospectively maintains a database of prostate cancer patients who are monitored with active surveillance. At the time of this study, there were 200 prostate cancer patients being monitored with active surveillance. Of those patients, 114 patients had an initial multiparametric MRI study that was performed before active surveillance started and at least one follow-up multiparametric MRI study that was performed after active surveillance began. The MRI findings were evaluated and correlated with pathology results, if available. RESULTS:Fourteen patients discontinued active surveillance because changes on follow-up MRI suggested progression of cancer. Follow-up MRI showed an enlarged or more prominent lesion compared with the appearance on a previous MRI in three (21.4%) patients, a new lesion or lesions suspicious for cancer in two (14.3%) patients, and findings suspicious for or confirming extracapsular extension in nine (64.3%) patients. Seven of the 14 (50.0%) patients had a biopsy after follow-up multiparametric MRI, and biopsy results led to tumor upgrading in six of the 14 (42.9%) patients. The duration of active surveillance ranged from 4 to 110 months. All patients received definitive treatment. CONCLUSION/CONCLUSIONS:The small number of patients with follow-up multiparametric MRI findings showing worsening disease supports the role of MRI in patients with early-stage prostate cancer. Multiparametric MRI is useful in monitoring patients on active surveillance and may identify patients with clinically significant cancer amenable to definitive treatment.

Background: While patient-derived xenografts (PDXs) offer a powerful modality for translational cancer research, a precise evaluation of how accurately patient responses correlate with matching PDXs in a large, heterogeneous population is needed for assessing the utility of this platform for preclinical drug-testing and personalized patient cancer treatment. Patients and methods: Tumors obtained from surgical or biopsy procedures from 237 cancer patients with a variety of solid tumors were implanted into immunodeficient mice and whole-exome sequencing was carried out. For 92 patients, responses to anticancer therapies were compared with that of their corresponding PDX models. Results: We compared whole-exome sequencing of 237 PDX models with equivalent information in The Cancer Genome Atlas database, demonstrating that tumorgrafts faithfully conserve genetic patterns of the primary tumors. We next screened PDXs established for 92 patients with various solid cancers against the same 129 treatments that were administered clinically and correlated patient outcomes with the responses in corresponding models. Our analysis demonstrates that PDXs accurately replicate patients' clinical outcomes, even as patients undergo several additional cycles of therapy over time, indicating the capacity of these models to correctly guide an oncologist to treatments that are most likely to be of clinical benefit. Conclusions: Integration of PDX models as a preclinical platform for assessment of drug efficacy may allow a higher success-rate in critical end points of clinical benefit.

Prostate cancer is the most common malignancy amongst American men. However, the majority of prostate cancer diagnoses are of low risk, organ-confined disease. Many men elect to undergo definitive treatment, but may benefit from focal therapy to maintain continence and potency. This review reports the mechanism of action and outcomes of emerging focal therapies for prostate cancer. We report the mechanism of action of focal cryotherapy, high intensity focused ultrasound, focal laser ablation, and irreversible electroporation. In addition, we reviewed the largest studies available reporting rates of urinary incontinence, erectile dysfunction, biochemical recurrence-free survival (ASTRO), and post-operative adverse events for each procedure. Each treatment modality stated has a unique mechanism in the ablation of cancerous cells. Genito-urinary symptoms following these studies report incontinence and erectile dysfunction rates ranging from 0-15% and 0-53%, respectively. Biochemical disease-free survival was reported using the ASTRO definition. Some treatment modalities lack the necessary follow-up to determine effectiveness in cancer control. No focal therapy studies reported serious adverse events. These minimally invasive procedures are feasible in a clinical setting and show promising functional and disease control results with short to medium-term follow-up. However, each treatment requires additional robust prospective studies as well as its own unique domain to determine biochemical recurrence free survival to properly determine their role in treatment of organ-confined prostate cancer.

Although prostate cancer is common in the western world and is associated with favorable overall survival, neuroendocrine prostate cancer is difficult to detect and is known to aggressively metastasize throughout the body. This subset of disease thus has a poor prognosis, and early detection and treatment of neuroendocrine prostate cancer may increase overall survival. We present a case of a now deceased 63 year old male with extensive epicardial, respiratory, hepato-bilary, adrenal, genitourinary, and osseous tissue metastasis.

Purpose. Active surveillance is an emergent strategy for management of indolent prostate cancer. Our institution's watchful waiting protocol, Active Holistic Surveillance (AHS), implements close monitoring for disease progression along with various chemopreventive agents and attempts to reduce unnecessary biopsies. Our objective is to report on the treatment rates of men on our AHS protocol as well as determine reasons for progression. Materials/Methods. Low risk and low-intermediate risk patients were enrolled in AHS at Winthrop University Hospital between February 2002 and August 2015. Our IRB-approved study analyzed survival rate, discontinuation rates, and definitive treatments for patients in our AHS cohort. Results. 235 patients met inclusion criteria. Median age and follow-up for the cohort were 66 (44-88) years and 42 (3-166) months, respectively. The overall survival for the cohort was 99.6% and the disease specific survival was 100%. A total of 27 (11.5%) patients discontinued AHS. Conclusion. The incorporation of chemopreventive agents in our AHS protocol has allowed patients to prolong definitive treatment for many years. Longer follow-up and additional studies are necessary to further validate the effectiveness of AHS.