International Prostate Cancer Update Archives

Radiation Oncology Perspective: Image-Guided Metastasis-Directed Therapy

Posted by Steven E. Finkelstein, MD, FACRO | Sep 2021

Steven E. Finkelstein, MD, FACRO, radiation oncologist with Florida Cancer Affiliates in Panama City, Florida, discusses 3 unique cases of recurrence after robotic-assisted laparoscopic radical prostatectomy and bilateral pelvic lymphadenectomy and their clinical management from a radiation oncology perspective. He introduces the first case of a patient with a PSA of 5.4 ng/mL and a Gleason score of 5+4 at the time of initial diagnosis. Dr. Finkelstein states that the recurrence became apparent once the patient’s PSA rose from .15 to .9 and a negative bone scan led to the initially planned treatment of post-prostatectomy radiotherapy (XRT). He explains that next-generation imaging (NGI) was then ordered and showed increased tracer uptake in an area of the left pelvis, leading the patient to begin a course of intensity-modulated radiation therapy and daily image-guided radiation therapy (IGRT). Dr. Finkelstein then moves on to the second patient, who had a PSA of 4.4 ng/mL and a Gleason score of 4+4 initially and whose recurrence was identified once their post-treatment PSA rose from .25 to 1. He describes how a negative bone scan led to initially planning a post-prostatectomy XRT, but when NGI found a sclerotic lesion in the middle right iliac bone, his treatment changed to stereotactic body radiation therapy (SBRT). Dr. Finkelstein then introduces the final patient, who had a PSA of 4.4 ng/mL and a Gleason score of 4+4 and whose recurrence was identified once their post-treatment PSA of .25 increased to 1. He states that, again, a negative bone scan led to planning post-prostatectomy XRT for the patient. NGI proved that XRT would have been insufficient by identifying a sclerotic lesion in the middle right iliac bone and 5 other bone metastases. Dr. Finkelstein concludes by noting that, due to NGI, the patient also received SBRT.

Phase 3 VISION Study of 177Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer

Posted by Daniel J. George, MD | Sep 2021

Daniel J. George, MD, Professor of Oncologic and Urologic Medicine and Surgery at Duke University, reviews the results of the VISION phase 3 study of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer. He begins by describing 177Lu-PSMA-617, explaining how it binds to PSMA and causes DNA damage and cell death in cancer. Dr. George then introduces the VISION study, discussing its two arms (standard-of-care, or SOC, and 177Lu-PSMA-617 based treatment vs. SOC alone), as well as its primary endpoints (radiographic progression-free survival, or rPFS, and overall survival). He also highlights the impact of an early dropout rate of 56% in the SOC arm which required enhanced study site education and communication to overcome and resulted in 2 study populations. Dr. George then summarizes the baseline characteristics of the patient populations before detailing the results. He states that 177Lu-PSMA-617 improved rPFS in OS, as shown by the SOC plus 177Lu-PSMA-617-based treatment arm having a higher median survival of 3-5 months. Dr. George then notes that 177Lu-PSMA-617 plus SOC had a 42% partial response rate, a 9.2% complete response rate, and an overall response rate of 50%, whereas SOC alone had a 3% partial response rate and no complete response rate. He states that 177Lu-PSMA-617 with SOC also created a 50% or greater decline in PSA in 46% of patients compared to SOC alone doing the same in only 7.1%. Dr. George discloses that fatigue, bone marrow suppression, dry mouth, nausea and vomiting, renal effects, second primary malignancies, and intracranial hemorrhage are all side effects of this treatment. He concludes that in a heavily pretreated and PSMA-enriched population 177Lu-PSMA-617 demonstrated clinically and statistically significant improvement in OS, rPFS, PSA, and objective responses.

The Prostate – Highlights of Prostate Cancer Advances As Covered in ASCO-SEP

Posted by Marc B. Garnick, MD | Sep 2021

Marc B. Garnick, MD, the Gorman Brothers Professor of Medicine at Harvard Medical School and the Beth Israel Deaconess Medical Center, provides a capsulated summary of key references from the ASCO Self-Evaluation Program (ASCO-SEP) 7. He also distills information of interest for practice change related to urologic oncology, particularly prostate cancer, published over the last 12-18 months. Dr. Garnick covers topics including: the emerging role and trends of MRI following elevated PSA values; the introduction of the first oral GnRH antagonist (relugolix) for endocrine management of locally advanced, biochemical recurrence or de novo metastatic castration-sensitive prostate cancer; improvements in overall survival (OS) with the addition of androgen receptor antagonists to androgen deprivation therapy; and approvals of three drugs for improving metastasis-free survival and OS in non-metastatic castration-resistant prostate cancer. Dr. Garnick then reviews ASCO, European Association of Urology (EAU), and ASTRO guidelines published during the COVID-19 pandemic and concludes by sharing data from within the ASCO-SEP chapter on genitourinary cancers that offer a global perspective on mortality disparities for prostate, bladder, kidney, testicular, and penile cancers. He finishes the presentation by pointing out a “sobering” difference in mortality-to-incidence ratios, a parameter to estimate health system performance, between high- and low-to-middle-income countries worldwide.

Review of Sentinel Assay for Prostate Cancer Diagnosis

Posted by Laurence Klotz, MD, FRCSC | Sep 2021

Laurence Klotz, MD, FRCSC, Professor of Surgery at the University of Toronto and the Sunnybrook Chair of Prostate Cancer Research, reviews the Sentinel Assay, a urine-based assay for detecting prostate cancer currently awaiting FDA approval. He notes that there are several significant needs in the pre-biopsy setting, including the need to increase the probability of a positive biopsy, and the need to reduce overdetection and the number of unnecessary biopsies. Dr. Klotz observes that there are several commercially-available biomarker assays that seek to help with this, all of which appear to work fairly well, although perhaps not quite as well as miR Scientific’s Sentinel Assay appears to. He explains that the Sentinel Assay is based on analysis of 442 urinary exosome microRNA sequences, and that it can identify small high-grade tumors that may be missed by imaging or biopsy. Dr. Klotz then summarizes the results of the one paper published on the Sentinel Assay so far, observing that its findings that the Sentinel prostate cancer test demonstrates a sensitivity of 94% and specificity of 92% are almost too good to be true. He presents as-yet-unpublished data that supports these findings, showing a 93% concordance between the Sentinel Assay and pathology. Dr. Klotz concludes that while validation is still needed, the Sentinel Assay appears to be an extremely accurate urine-based assay that will be easy to ship and use.

Early Diagnosis of Prostate Cancer: A Path Forward

Posted by E. David Crawford, MD | Sep 2021

E. David Crawford, MD, Editor-in-Chief of Grand Rounds in Urology and Professor of Urology at the University of California, San Diego, discusses the challenges of early detection of prostate cancer (PCa), the role of markers in identifying patient risk, and the impact of early detection. He begins by acknowledging the limitations of prostate-specific antigen (PSA) testing alone and notes that the United States Preventive Services Task Force (USPSTF) has raised concerns about PCa early detection, asserting that there is too much overdiagnosis and overtreatment. Because most diagnostic testing is completed by primary care physicians (PCPs) who may not understand the nuances of PSA testing, Dr. Crawford recognizes that PCPs need a simple message from urologists. He states that a PSA of >1.5 ng/ml is a good surrogate for benign prostatic hyperplasia (BPH), prostatitis, and PCa risk, and explains that patients with a PSA of 1.5 ng/ml to 4.0 ng/ml may be in a “danger zone” and require additional testing. Dr. Crawford argues, however, that an abnormal PSA alone should not guide biopsy decisions. Rather, he suggests that prostate cancer markers (PCMs) for patients with elevated PSA can better risk-stratify patients and identify significant cancers, enabling many to avoid biopsy. Dr. Crawford cites the example that using SelectMDx as a risk-stratification tool for biopsy-naive men avoids unnecessary biopsies in 38 percent of patients, minimizes detection of low-grade PCa, and misses only 10 percent of high-grade PCa. Further, using mpMRI in all patients had the highest net benefit, allowing 49% of patients to avoid biopsy and missing only 4.9 percent of high-risk PCa. However, if mpMRI availability is limited or expensive, using mpMRI-only in SelectMDx-positive patients is a good alternative strategy. Dr. Crawford concludes by outlining a diagnostic process whereby doctors may refer a patient to a urologist, repeat PSA testing, and incorporate PCM to better determine the risk of significant cancer as well as the need for biopsy for their patients with an elevated PSA.