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Emerging Treatments for BCG Unresponsive Non-muscle Invasive Bladder Cancer

Amirali Salmasi, MD, Assistant Professor of Urology at the University of California, San Diego, discusses available and emerging treatments for bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC). He begins by giving a brief history of intravesical BCG and explaining how BCG works, before moving on to discuss treatments for BCG-unresponsive NMIBC. Dr. Salmasi observes that valrubicin was the best available treatment for a long time, but suggests that some of the many emerging treatments may prove superior. He then summarizes recent and ongoing research into various potential therapies for BCG-unresponsive NMIBC, including: sequential gemcitabine and docetaxel; intravesical cabazitaxel, gemcitabine, and cisplatin; chemohyperthermia treatment; CG0070, an oncolytic adenovirus; superagonist N-803; intravesical nadofaragene firadenovec gene therapy; and pembrolizumab. Dr. Salmasi concludes that, for the moment, the gold standard treatment for a patient with BCG-unresponsive bladder cancer remains radical cystectomy, but he argues that if someone is not eligible for or turns down cystectomy, pembrolizumab is now the go-to rather than valrubicin, although this may change depending on the results of some of these ongoing trials.

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Representative Murphy’s Vision for Medical Reform

Congressman Gregory F. Murphy, MD, a practicing urologist and the Representative from North Carolina’s 3rd District, shares his vision for medical reform to help cut costs, ensure appropriate physician reimbursement, and improve care with E. David Crawford, MD, Editor-in-Chief of Grand Rounds in Urology and Professor of Urology at the University of California, San Diego. Dr. Crawford congratulates Rep. Murphy on his recent assignment to the House Ways and Means Committee, where his position on the Subcommittee on Health will allow him to help set the agenda on medical reform. Dr. Murphy lists the top issues he feels need to be addressed to move medicine forward, including cutting regulation, increasing predictability in what doctors are going to get paid, and improving the accessibility of healthcare to the average American. Dr. Crawford and Rep. Murphy elaborate on these topics, first commenting on the rise of middlemen in healthcare, and discussing how this can limit doctors’ ability to make the correct choices for their patients. They then consider causes and potential solutions to high prices, from getting rid of direct-to-consumer advertising of pharmaceuticals to having doctors take the lead on cutting costs by choosing more inexpensive treatments and reducing waste. Rep. Murphy also comments on the current status of the No Surprises Act, which is intended to end high out-of-network medical bills. Dr. Crawford and Rep. Murphy conclude with a brief discussion of the VA.

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‘Hand Size’ and Healthcare

Grand Rounds in Urology Contributing Editor Neil H. Baum, MD, Professor of Urology at Tulane Medical School, considers how common healthcare metrics can be faulty, much like the idea that larger hand size signifies a better quarterback. He explains that many in the football industry have long assumed that small hands result in fumbles and bad throws, and have therefore used hand size as a metric when drafting quarterbacks. However, as a recent article about successful, small-handed quarterbacks Patrick Mahomes and Joe Burrow demonstrates, this metric is inherently flawed. Dr. Baum suggests that this is a useful story to keep in mind when considering certain common healthcare metrics and concepts that are not as infallible or relevant as they seem. For instance, he notes that urologists commonly measure erectile dysfunction post-retropubic radical prostatectomy or external radiation therapy, but patients are actually far more interested in continence than sexual function. Dr. Baum also argues that common metrics like resting heart rate and body-mass index actually provide less useful health information than heart rate variability and waist circumference, respectively. He then observes that even one of the most widely-held beliefs in healthcare—that doctors have to see and touch a patient in order to properly treat them—has proven inaccurate with the rise of efficient, affordable telemedicine. Dr. Baum concludes that healthcare professionals should challenge conventional wisdom, and that doing so may help with finding new metrics and new methods for treating patients.

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Asymptomatic Stones: Treat or Observe?

Manoj J. Monga, MD, FACS, Professor and Chair of Urology at the University of California, San Diego, suggests a situational approach to asymptomatic renal stone treatment based on outcomes data. Dr. Monga explains that asymptomatic renal stones are very common and are diagnosed in some 2 million patients per year. He notes that asymptomatic stones cause significant psychological distress in patients, and in fact tend to worry more than other stone patients. Dr. Monga also clarifies that asymptomatic stones often do not remain asymptomatic, citing data published in the Journal of Endourology showing that 26% of patients ultimately require intervention, 48% experience pain, 55% experience stone growth, and 77% experience any of the previously stated outcomes within 4 years of an asymptomatic stone being identified. He then shows that risk can be further stratified based on stone size and location, explaining that a stone in the renal pelvis is guaranteed to progress while a small upper pole stone is more likely to pass. Dr. Monga states that in most cases asymptomatic stone patients should be treated. He then summarizes the different treatments available for renal stones, observing that patients tend to select the less-invasive shockwave treatment over ureteroscopy even though it is less effective. He states that shockwave treatment’s efficacy varies based on the location and size of the stone, and that this should be discussed with patients. Dr. Monga concludes that stones less than 4mm should be observed and those between 4mm and 10mm should undergo shockwave treatment, while larger stones may require ureteroscopy.

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Industry Perspective: Developing the Most Sensitive Urine Test for Bladder Cancer

Nam W. Kim, PhD, Co-Founder and Chief Executive Officer & Chief Technology Officer of KDx Diagnostics, summarizes the challenges of bladder cancer diagnosis and introduces the URO17 test as an overall solution. He begins by discussing the unmet clinical need in bladder cancer for an accurate, non-invasive test due to difficult diagnosis of the disease. Dr. Kim then describes the URO17 urine test as a diagnostic that detects keratin-17 (K17) protein expression in urine cytology samples. He then reviews several studies on the efficacy of the URO17 test. Dr. Kim explains that the first study found that K17 promotes nuclear export, subsequent degradation of tumor suppressor p27 KIP1, and sustained proliferation and tumor growth by overcoming G1-S checkpoint in cancer cells. He also discusses KDx’s initial study evaluating K17 expression in bladder tissue that found that there was a significant increase in both low and high grade cancer when compared to normal tissues and showed the URO17 test to have 100% sensitivity and 96% specificity in detecting bladder cancer cells in recurrent bladder cancer patients. A study of the URO17 test’s efficacy in the hematuria population found that the test has a sensitivity of 100% and 92.6% specificity in detecting new bladder cancer. Dr. Kim concludes by describing a final study that looked at K17 expression in recurrent cancer and hematuria populations and which found similar results to the previous studies.

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