Biopsy Collection for Men Undergoing Brachytherapy for Prostate Cancer

Many patients with metastatic prostate cancer who succumb to the disease are initially diagnosed with localized prostate cancer, where treatment has the potential to be curative. For men initially diagnosed with high risk or locally advanced prostate cancer, nearly 50% develop recurrence after primary therapy and can eventually progress to life-threatening metastatic disease. Combined androgen deprivation therapy (ADT) with ionizing radiation (IR) is the current mainstay of therapy for such men with high-risk prostate cancer. While it is likely that undetected, microscopic disseminated disease leads to the inability to cure in some men, there is also emerging evidence that escalating local therapy may still have benefit. It has been reported that metastasis-free survival and overall survival were significantly improved in men with high-risk localized prostate cancer treated with external beam radiotherapy (EBRT) with brachytherapy boost compared to men treated with EBRT alone, or with radical prostatectomy. The observation that enhanced IR-based local therapy could improve outcomes supports the notion that it is not microscopic systemic disease alone that leads to treatment failures of high-risk prostate cancer, but that more aggressive local management could still play a significant role.

A key question in the management of high risk prostate cancer is how can the investigators predict whether a patient with local or metastatic prostate cancer will have complete response with current IR-based therapy paradigms, or if patients would benefit from more aggressive dosing regimens despite a potential for increased adverse effects. A major limitation to developing effective strategies for predicting treatment response to conventional vs. more aggressive dosing regiments has been a paucity of tissues from patients undergoing radiation therapy, including at baseline and during follow up, as well as a lack of the molecular, cell biological, and biochemical states of the cancer and microenvironmental cells in such tissues. The availability of such tissues and data can accelerate the discovery process of identifying novel biomarkers and therapeutic strategies for patients with prostate cancer.

Thus, a more comprehensive understanding of the tissue microenvironment at base line and following radiation therapy may inform improved strategies in radiation dosing, as well as complementary neoadjuvant and adjuvant treatments to achieve complete response in organ-confined disease in the future. Such an understanding of the tissue and biological response of prostate cancer to radiotherapy may also provide insights to enhance IR-based therapy of metastatic and oligometastatic disease, for both palliative and perhaps life-prolonging intent.

The primary goal of this tissue collection protocol is to establish a framework for the acquisition and banking of biospecimen collected from men undergoing brachytherapy. Biopsy of the prostate is an invasive procedure; however, in this tissue collection protocol, biopsies are acquired intraoperatively while patients are prepped for brachytherapy seed placement, thus minimizing the discomfort as well as the inconvenience of the biopsy procedure for patients. A subset of these patients will choose to have a 2 year confirmatory biopsy to detect the absence or persistence of disease. Biopsy cores collected 2 years post-IR therapy will also be included in the investigators' correlative studies. These biopsies will provide a valuable resource for molecular and pathological assessments. To extract the maximal amount of information from these biopsy specimens, the investigators will utilize comprehensive genomic, pathological, and biochemical analyses including DNA-seq, RNA-seq, methylome analysis, single cell sequencing, immunohistochemistry (IHC)/immunofluorescence (IF). The investigators will also collect and maintain a database of the clinicopathological parameters and follow up information for these specimens. The biobank will thus represent a bank of tissues as well as the correlative measurements on those tissues.