Memorial Sloan-Kettering Cancer Center

Comparative Outcomes: Prostate Brachytherapy vs. EBRT vs. SBRT for Low/Intermediate Risk Disease

Posted by Michael J. Zelefsky, MD | Apr 2022

As part of a special course on brachytherapy for prostate cancer from the American Brachytherapy Society (ABS) and Grand Rounds in Urology, Michael J. Zelefsky, MD, Vice Chair of Clinical Research in the Department of Radiation Oncology and Chief of the Brachytherapy Service at Memorial Sloan Kettering in New York City, compares outcomes for prostate brachytherapy vs. external-beam radiation therapy (EBRT) vs. stereotactic body radiotherapy (SBRT) for patients with low- and intermediate-risk disease. Dr. Zelefsky explains that when comparing outcomes, the focus is on toxicity after therapy and the efficacy of therapy. He also notes several limitations in comparing different radiotherapeutic modalities as well as dramatic technological innovation over the last 10 years that have greatly improved radiotherapy delivery. While this has been revolutionary in the treatment of disease, it creates what he calls “a moving target” when comparing outcomes because of the difficulty in comparing studies completed at various points in this technological revolution. Dr. Zelefsky cites a comparative study of patient-reported quality-of-life (QOL) outcomes after SBRT, low-dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy for prostate cancer. Another study compared patient-reported QOL following SBRT and conventionally fractionated EBRT compared with active surveillance in those with localized prostate cancer. He reviews highlights from five-year outcomes of the HYPO-RT-PC randomized, non-inferiority, phase 3 trial that examined ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer, including that the estimated failure-free survival at five years was 84 percent in both treatment groups. Dr. Zelefsky notes that genitourinary and gastrointestinal toxicity were similar in both groups as well. He presents a chart illustrating urinary symptoms post-therapy which shows that while LDR has a higher rate of acute grade two urinary symptoms, late urinary toxicity and late urinary incontinence are similar across LDR, EBRT, and SBRT. Dr. Zelefsky outlines the benefits of prostate brachytherapy for favorable and intermediate-risk disease, pointing out that it has the most ablative potential, prostate-specific antigen nadirs are generally significantly lower than with EBRT, and post-treatment biopsy outcomes are positive in just seven percent of patients. He compares this with data showing that EBRT results in post-treatment positive biopsy outcomes of approximately 25-30 percent and data showing that SBRT with a dose of 40 Gy results in post-treatment positive biopsy outcomes of 11 percent. Dr. Zelefsky suggests then that SBRT has more ablative potential than EBRT but that brachytherapy has even more ablative potential than either of these. Finally, Dr. Zelefsky summarizes by explaining how these findings help inform patient decisions and treatment selection, pointing out that prostate brachytherapy may be preferable for the younger patient with few urinary symptoms, while patients with significant urinary symptoms may prefer SBRT. Patients with a larger prostate who may otherwise require downsizing with ADT may opt for SBRT over brachytherapy.

Urologic Perspective on the Current and Emerging Role of Multi-Modality Imaging and Radiogenomics

Posted by Mohummad Minhaj Siddiqui, MD | Feb 2022

Mohummad Minhaj Siddiqui, MD, Associate Professor of Surgery at the University of Maryland School of Medicine and Chief of Urology at the Baltimore VA Medical Center in Redwood, Maryland, discusses the role of precision imaging and genomics in managing localized prostate cancer. He first considers how treatment strategies will vary based on cancer aggressiveness, ranging from active surveillance in low-risk cancer to multimodal treatment in advanced and metastatic cancer. Dr. Siddiqui cites the PROMIS study which stratified risk of significant cancer based on MRI suspicion score of lesions. He points out that even at that high end of the scale, MRI identified cancers in some patients that either had insignificant or no cancer, demonstrating that imaging cannot replace biopsy. Equally important, at the low end of the scale, half of patients have cancer not shown in the scan. Dr. Siddiqui adds that while a scan may not suggest high-risk cancer, this is not the same as not having cancer. He then discusses the growth of genomic profiling in understanding genomic characteristics of prostate cancer. Genomic profiling is available for different stages of prostate cancer workup from susceptibility characterization to disease risk stratification and prediction of treatment response. The GC score in genomic characterization has similar limitations as imaging, leading to the question of whether these two modalities are capturing the same underlying issue or complementing each other. Dr. Siddiqui then describes how he uses imaging in a surgical setting for margin size and extracapsular extension at radical prostatectomy. He concludes that while it is not perfect, advanced imaging can improve risk stratification and assist with cancer staging and treatment planning. Similarly, genomics can also improve risk stratification and can reduce interventions like adjuvant radiation.

Transperineal Biopsy & Classification of Risk Using Novel Gleason Pattern Quantification

Posted by Behfar Ehdaie, MD, MPH | Jan 2022

Behfar Ehdaie, MD, MPH, a urologic surgeon at Memorial Sloan Kettering Cancer Center in New York City, outlines the role of Gleason pattern quantification on prostate cancer outcomes. He explains data indicating biopsy pathology primary Gleason grade (GG) is prognostic of disease recurrence after treatment. Research showed an association between the total length of Gleason pattern 4 across all biopsy scores and worse pathologic outcomes among men with GG2 prostate cancer. Dr. Ehdaie explains the total length of Gleason pattern 4 across all biopsy cores best predicts risk of adverse pathology post radical prostatectomy (RP) compared to overall percentage or maximum percentage pattern 4 in a single core. Dr. Ehdaie then asserts that multi-parametric magnetic resonance imaging (mpMRI) and image-based tracking software has improved detection of higher grade prostate cancer. He displays data that show MR-targeted prostate biopsy improves detection of higher grade disease for men on active surveillance. Dr. Ehdaie explains 22 percent of patients on active surveillance experienced an increase in Prostate Imaging Reporting and Data System (PI-RADS) score on surveillance MRI, emphasizing that patients do experience changes in imaging that can be correlated with outcomes. He then explains the shift to transperineal biopsy and points out it enables systematic cores to be taken in a gridlike fashion that offers opportunity for standardization. He displays data comparing transperineal and transrectal biopsy that indicate transperineal prostate biopsy improves detection of higher-grade prostate cancer for men under active surveillance. Dr. Ehdaie concludes that transperineal biopsy may provide a standardized technique for better sampling and, consequently, better classification of risk, emphasizing that technology capable of transitioning from transrectal to transperineal prostate biopsy is key. Dr. Ehdaie concludes his talk by emphasizing that the incorporation of total biopsy length Gleason pattern 4 improves risk classification for men with GG2 and GG3 prostate cancer. This can help select patients for active surveillance and can develop triggers to recommend subsequent treatment. Additionally, Dr. Ehdaie reiterates that adding systematic biopsy cores to MR-targeted biopsy improves overall detection of higher-grade cancer, and seamless transition from transrectal to transperineal biopsy enables a template-based biopsy technique to standardize sampling for risk stratification.

Use of MRI-Targeting Increases Overdiagnosis and Overtreatment

Posted by Andrew J. Vickers, PhD | Jan 2022

Andrew J. Vickers, PhD, Attending Research Methodologist at Memorial Sloan Kettering Cancer Center in New York City, asserts that the current diagnostic use of MRI-targeting leads to overdiagnosis and overtreatment. He begins by stating that methods of detection such as systematic biopsies and measuring prostate-specific antigen (PSA) don’t tend to lead to underdiagnosis and undertreatment. To illustrate the reasons MRI-targeting leads to overdiagnosis and overtreatment, he displays data showing that in MRI-targeted biopsy the method of grading the core samples leads to higher grading of overall disease. Dr. Vickers points out that Gleason grade is not an inherent property of a tumor, but is instead a surrogate outcome. He then illustrates that biochemical recurrence (BCR) risk and risk of death for high-grade cancer on surgical pathology is dramatically reduced for clinically low-risk patients. Dr. Vickers cites the PRECISION trial which indicated that the MRI-targeted biopsies found far fewer low-grade cancers and more high-grade cancers, but the overall number of cancers identified was essentially the same. Dr. Vickers asserts that these results are consistent with a scenario whereby the technique simply characterized some of the low-grade cancers as high-grade. He then cites another study during which patients had both a systematic and an MRI-targeted biopsy; the MRI targeting identified more cancers that, in turn, led to more treatment. Dr. Vickers suggests this is problematic and opines that urologists do not need to find high-grade cancer in men with low-grade cancer on systematic biopsy. He supports his assertions by citing another study that followed 2,907 men for 17 years. Of those men, there were five cases of metastasis, with just two being potentially preventable. He also cites the European Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam study which followed over 3,000 men with a negative sextant biopsy for 11 years and recorded just seven (.02 percent) deaths during that time. Dr. Vickers concludes that the number of men whose prostate cancer would have to be identified and treated in order to save one life is very large and MRI-targeting is leading to excessive overdiagnosis and overtreatment. Dr. Vickers then states that while there should be a clear clinical indication for MRI, such as negative biopsy with rising PSA, the current National Comprehensive Cancer Network (NCCN) guidelines call for treatment irrespective of the method of detection. Dr. Vickers concludes there is an urgent need for more restrictive use of MRI-targeting, evolved treatment guidelines for MRI-detected tumors, and additional research on oncologic risk of MRI-detected tumors.

MRI-Guided Focal Therapy: Initial Quality-of-Life and Oncologic Outcomes

Posted by James A. Eastham, MD, FACS | Oct 2021

James A. Eastham, MD, FACS, Peter T. Scardino Chair in Oncology and Chief of the Urology Service in the Department of Surgery at Memorial Sloan-Kettering Cancer Center in New York, discusses initial results from a clinical trial examining safety, quality-of-life outcomes, and oncological outcomes of MRI-targeted focal therapy for patients with intermediate-risk prostate cancer. He explains that the goal with magnetic resonance (MR)-guided focused ultrasound (MRgFUS) therapy is to try to treat as little of the prostate gland as possible and that the difficulty lies in accurately targeting the area of the prostate to be destroyed. Dr. Eastham cites the limitations of MRI and asserts the importance of finding better ways to target areas for treatment. He then explains the clinical trial methodology and its primary endpoints, which focus on the safety of the procedure, as well as its examination of quality-of-life and oncologic outcomes. Dr. Eastham describes characteristics of the patient cohort and reviews initial results indicating the procedure is safe, with no serious adverse events observed among the 101 participants. According to six-month post-procedure biopsy results, 91 percent of men had no evidence of prostate cancer in the treatment area. Comparatively, however, six-month post-procedure biopsies of the whole gland showed the procedure does not adequately target the lesions or the areas with more significant cancers; the percentage of men with no evidence of GG≥2 prostate cancer anywhere in the prostate gland dropped to 78 percent. Dr. Eastham explains that this is a failure to appropriately identify all significant lesions, despite the fact that study participants underwent two separate biopsies. While few patients have yet undergone 24-month biopsies, of those who have, only 7.3 percent had GG≥2 detected in the treatment area. Additional results show decreased PSA levels after treatment that stabilized after six months. Dr. Eastham then presents data showing that with focal ablation, men do experience some decline in erectile function. He explains that this is one reason why low-risk patients may be better suited to active surveillance. However, study participants generally did not experience a decline in urinary function. Dr. Eastham concludes by reiterating that 24-month data is forthcoming. He explains that short-term data show this is a safe, well-tolerated procedure that may enable patients to consider a tissue-preserving approach and defer or avoid radical therapy. Looking to the future and phase 3 trials, Dr. Eastham explains that a meaningful endpoint will be a delay in disease progression as well as the consequent radical prostatectomy or radiation therapy.