2022

A Biochemical Definition of Cure Following Brachytherapy of Prostate Cancer

Posted by | Apr 2022

As part of a special course on brachytherapy for prostate cancer from the American Brachytherapy Society (ABS) and Grand Rounds in Urology, Juanita M. Crook, MD, FRCPC, Professor of Radiation Oncology at the University of British Columbia in Kelowna, discusses the development of a biochemical definition of cure following low-dose-rate (LDR) prostate brachytherapy. She begins with some background, explaining that the interpretation of post-radiation PSA values has been challenging. She relates that the 1996 ASTRO consensus conference defined biochemical failure as 3 consecutive rises after the nadir with failure backdated to midway between the nadir and the first rise, while the 2005 Phoenix consensus conference defined biochemical failure as 2 ng/ml > nadir, a definition still widely used today. Dr. Crook emphasizes that neither definition was meant to be a trigger for intervention, and neither attempted to define cure. She then discusses research on the importance of PSA nadir in LDR brachytherapy which showed that if PSA at 4 years was less than 0.2 to 0.4 ng/ml, patients tended to do well, but if it was greater than 1.0, the majority were going to fail. Dr. Crook considers another study on long-term PSA stability after LDR brachytherapy which found that 86% of patients had stable PSA at a median followup of 89 months. She also briefly notes that a study of intermediate-risk patients undergoing external beam radiation therapy (EBRT) + high-dose-rate brachytherapy boost found similar results to the studies of LDR brachytherapy regarding the importance of PSA nadir. Dr. Crook then goes into detail about a study she and her colleagues conducted to define a biochemical definition of cure following LDR brachytherapy by identifying a PSA threshold value at an intermediate follow-up time that is associated with long-term (10-15 year) freedom from prostate cancer. She explains that by using prospectively-collected data sets combined from 7 institutions, she and her colleagues were able to determine that patients with a PSA ≤ 0.2 ng/ml by 4-5 years have a 99% probability of being free of clinical failure at 10-15 years. Dr. Crook concludes that PSA ≤ 0.2 ng/ml should be adopted as biochemical definition of cure for comparison with surgical series, but highlights that those patients not achieving this threshold PSA should not be considered as having “failed” but should continue to be monitored with the understanding that they are at higher risk of subsequent clinical failure.

Read More

Overview of the State of Genetic Testing and Future Applications in Prostate Cancer

Posted by | Apr 2022

Brian T. Helfand, MD, PhD, Chief of the Division of Urology and the Ronald L. Chez Family and Richard Melman Family Endowed Chair at NorthShore University HealthSystem in Evanston, Illinois, discusses current and potential future applications of genetic testing in prostate cancer screening and treatment. He explains that genetic testing has applications throughout the patient journey. At the prevention and screening stage, genetic testing can determine which men will benefit from screening. At the diagnosis stage, it can determine which men will benefit from biopsy. During early-stage disease, genetic testing can help identify which men will benefit from definitive treatment. Finally, during late-stage disease, genetic testing can identify the men that will benefit from advanced therapies. Dr. Helfand notes that there are two kinds of genetic testing, germline and somatic, and not all tests are relevant at all stages of the patient journey. He then gives an overview of germline genetic testing’s role in screening, arguing that because family history, rare pathogenic mutations (RPMs), and genetic risk score (GRS) all measure risk independently, a comprehensive inherited risk assessment should include all three tools. Dr. Helfand particularly focuses on GRS, defining it as a number calculated based on the cumulative variation across multiple single nucleotide polymorphisms (SNPs), which is then used to provide an estimate of disease risk. He notes that GRS is simple to interpret and more informative than family history. Dr. Helfand also observes that GRS is correlated with number and laterality of tumor cores. GRS, he argues, is useful for risk stratification for both screening and active surveillance. He notes that RPMs can help with stratification in terms of disease aggressiveness. Dr. Helfand concludes by arguing that genetic testing for prostate cancer will be pivotal in the future and should be included in guidelines for both prevention and screening.

Read More

Lyndon Johnson and His Kidney Stone

Posted by | Apr 2022

Grand Rounds in Urology Contributing Editor Neil H. Baum, MD, Professor of Urology at Tulane Medical School, highlights the importance of imagining how the United States healthcare system could change by reflecting on how different the world would be had Lyndon Johnson’s kidney stone not been successfully removed. He explains that in 1948, Johnson was running for a US Senate seat and was deadlocked against the favorite, when he developed an obstructing kidney stone in the upper third of his ureter. He thought he would require a ureterolithotomy, but did not want to since that might require him to drop out of the race. Dr. Baum explains that Johnson met with Dr. Gershom Thompson at the Mayo Clinic for a second opinion, and Thompson agreed to try an endoscopic stone removal, even though he had never before removed a stone in the upper third of the ureter. Thompson was successful, and Johnson had a prompt recovery, allowing him to return to the campaign and win. Dr. Baum notes that Johnson’s recovery raises several “what if” questions, such as “how might the world have changed if LBJ had not had a successful endoscopic retrieval of a proximal ureteral stone and been unable to win his Senate race?” Dr. Baum considers Johnson’s legacy as President of the United States, from passing the Civil Rights Act to accelerating US military involvement in Vietnam. He then asks, “what if we did not have the two government healthcare programs, Medicare and Medicaid, that were instituted and approved during the Johnson Administration?” This leads him to ask a whole series of “what if” questions, such as “what if we had a single payer system?” and “what if we could put more enjoyment back in the practice of medicine?” He concludes that it may be time to ask some “what if” questions, and he suggests that by doing so, it may be possible to find ways to repair the current healthcare system rather than seeing it as fundamentally immutable.

Read More
Industry Perspective: The Oncotype DX Genomic Prostate Score Assay Test

Industry Perspective: The Oncotype DX Genomic Prostate Score Assay Test

Posted by | Mar 2022

Daniel Shoskes, MD, FRCSC, Medical Director in Medical Affairs for Urologic Oncology at Exact Sciences, and Emeritus Professor of Urology at the Cleveland Clinic, explains how Exact Science’s Oncotype DX Genomic Prostate Score (GPS) assay test works, and considers its utility in guiding treatment decisions. He begins by discussing why genomics are of interest in relation to prostate cancer, highlighting the fact that abnormal gene expression may lead to abnormal/unregulated cell growth, which in turn may lead to irregularity on direct palpation, altered appearance on MRI, elevated PSA, and disordered gland appearance on histology. The researchers at Exact Sciences, Dr. Shoskes explains, hypothesized that these clinical features might not completely capture the prognosis of the patient, and that looking at gene expression directly might give further information. He relates how the researchers selected genes for association with metastasis and then refined the list for associations with death and adverse pathology. They found 17 genes that predicted recurrence in both the primary and highest Gleason patterns, and also had consistent analytical performance and expression in samples as small as 1mm. Dr. Shoskes then discusses how predictive this 17-gene assay is, noting that the GPS assay is an independent predictor of metastasis and prostate cancer death within 10 years of radical prostatectomy and may be associated with prostate cancer outcomes for up to 20 years after diagnosis. He highlights that incorporating the GPS result with NCCN Guidelines can provide a comprehensive risk profile. Dr. Shoskes considers how the GPS assay can be used practically, explaining that for low-risk patients, it can help inform shared decision-making for active surveillance vs. immediate therapy with curative intent, while for higher-risk patients, it can help inform the decision for treatment intensification. He concludes that the Oncotype DX GPS assay provides meaningful, actionable information on the biologic potential of prostate cancer independent of clinical, pathologic, and radiographic data.

Read More