A pivotal phase II trial of a novel MRI-guided ultrasound ablation treatment exceeded its primary efficacy endpoint of PSA decline in men with organ-confined prostate cancer.

In the prospective, open-label study of MRI-guided transurethral ultrasound whole-gland ablation (TULSA-PRO), 96% of men had a PSA decrease of at least 75% at 1 year. Approximately 80% of the men who entered the study with Gleason grade group 2 (Gleason score 7) prostate cancer no longer had evidence of Gleason grade group 2 disease at 1 year. Nearly two-thirds of men had a complete histologic response based on biopsy, principal investigator Scott Eggener, MD, reported at the AUA annual meeting in Chicago.

Rates of severe treatment-related toxicity were low, said Dr. Eggener, director of the Prostate Cancer Program at the University of Chicago.

Prostate cancer in 9/11 responders: Study explores mechanism of action

The phase II study, conducted at 13 centers in the United States, Canada, and Europe, included 115 men with a median age of 65 years. Median pre-treatment PSA was 6.3 ng/mL and maximum PSA was 15.0 ng/mL. All men had Gleason grade group 2 or lower prostate cancer. Two-thirds of study participants had intermediate-risk disease, and the remainder had low-risk disease. More than 80% of men had Gleason grade group 2 or high-volume Gleason grade group 1 cancer, which is generally considered to be clinically meaningful disease, Dr. Eggener noted.

The intent of treatment was whole-gland ablation with sparing of the urethra and urinary sphincter. The procedure is performed entirely within the MRI suite under general anesthesia to eliminate motion. An ultrasound device, placed transurethrally under MRI guidance, continuously rotates and robotically delivers ultrasound waves peripherally to a predetermined contour around the prostate. Colorimetric feedback indicates when the target temperature of approximately 57 degrees Celsius is reached.

Following treatment, an MRI is provided to confirm the ablation margin. A suprapubic tube is placed for 2 weeks.

The procedure is capable of treating all sizes of prostates, Dr. Eggener said. It is not a form of high-intensity focused ultrasound, which is performed transrectally and has a different mechanism of applying ultrasound energy, he pointed out.

In the current study, the primary endpoint of PSA reduction ≥75% was achieved in 110 of 115 men (96%). The FDA-approved protocol’s pre-established definition of success was a PSA decrease of ≥75% in 50% of patients.

“[The trial] overachieved on the PSA-based primary endpoint of what was considered success or failure,” Dr. Eggener said.

The median reduction in PSA was 95%. “Impressively, the median PSA nadir was 0.34 ng/mL. There was dramatic gland reduction,” Dr. Eggener said, with the pre-treatment median perfused prostate volume of 41 cc declining to 4 cc at 1 year following treatment-a 90% decrease.

In terms of safety, nine of 115 men (8%) experienced a grade 3 adverse event, with infection (4%) being the most common. One case each of urinary retention, urinoma, ileus, deep-vein thrombosis, urethral stricture, and urethral calculus was reported.

Of 112 patients on whom continence data were available at 1 year, 1% were incontinent (more than one pad per day). At 1 year, 3.8% of the men had a new increase in their daily leakage of urine.

At 1 year, 20% of men had grade 2 erectile dysfunction, and 69 of 92 (75%) who were potent prior to treatment maintained erections suitable for ­penetrative intercourse.

Among 68 men with pre-treatment intermediate-risk Gleason grade group 2 disease, 54 (79%) were free of Gleason grade group 2 disease on 1-year biopsy. Complete histologic response was seen in 72 off 111 patients (65%). Of 39 positive biopsies, 16 (41%) were clinically insignificant.

On multivariate analysis, three factors predicted the likelihood of ongoing presence of Gleason grade group 2 disease: presence of intraprostatic calcifications at screening, MRI thermal coverage of target volume, and PIRADS ≥3 lesion at 1-year post-treatment MRI 

Fat in abdomen, thigh linked to higher risk of aggressive prostate cancer

With the caveat that TULSA-PRO remains investigational, Dr. Eggener was asked which prostate cancer patient he would consider an ideal candidate if the treatment was granted regulatory approval.

“I would argue that it’s a guy who’s otherwise healthy, has Gleason 7 cancer, and understands the pros and cons of this approach,” he said. “Similar to other management options, it is not the ‘holy grail’; however, this could potentially be a nice addition to the menu of options for a guy that needs treatment, a menu that is getting larger and larger. Considerably more follow-up, trials, and data are required to better understand the long-term implications of this novel treatment modality.”

Profound Medical, the maker of the TULSA-PRO device, announced in May 2019 that its 510(k) application for premarket clearance cleared the FDA’s acceptance review. Follow-up will continue for 5 years.

Dr. Eggener is a paid consultant to Profound Medical.

Articles

Novel US ablation therapy shows significant PSA effect

What are some common mistakes physicians make when it comes to financial planning?

Not every physician is financially successful. It takes planning and execution to achieve your financial goals. However, success is not always dictated by what you do right as much as by what you may do wrong. Time and time again, we see physicians make avoidable mistakes that hinder or delay their ability to reach their financial goals.

 The number one reason we see physicians fail financially is procrastination. Whether from educational programs, self-research, or working with a financial professional, physicians know what they need to do to become financially successful. However, too often we hear physicians say, “Life gets in the way.” Work, family, and hobbies prevent physicians from devoting the time necessary to get their financial lives in order. The longer the wait, the more difficult it is to get on track.

 Vague goals often result in vague plans, and when you have a vague plan, it is easy to deviate from that plan and get off track. It is important to be specific about your goals so you can design a detailed plan for reaching them. For example, when thinking of your retirement goal, at what age do you what to retire? What level of income do you want in retirement? What sources are your savings coming from? What rate of return will you need to earn on your investments? Be specific so you can design a plan for reaching your goals.

How to assemble your financial professional network

Compounding interest is a powerful tool for growing wealth, and the key is saving and investing early so the investment has more opportunity to compound. The cost of waiting is substantial. If you wanted to save $1,000,000 by age 66 (assuming an 8% rate of return), you would have to save $671 per month if you started at age 35, $1,698 per month at age 45, and $5,466 per month at age 55. Many physicians wait too long and don’t have the resources to save large amounts due to other financial obligations.

 An investment strategy holds a physician accountable to what types of investments they will purchase, when they will get in and out of the market, and what their asset allocation will be. The investment strategy protects physicians from themselves so they don’t react emotionally when markets are performing very well or performing poorly. It keeps them steady, so they are not tempted to do something not in their own best interest.

Simply put, many physicians don’t have enough disability and life insurance. Without adequate coverage, your financial goals and the goals of your family are at risk in the event of a long-term disability or your premature death. Protect yourself so you and your family can still reach financial goals even if you are unable to work or if you die early.

Frequently, we see physicians start splashing the cash right out of their residency or fellowship. They buy a big home or new car, eat at fancy restaurants, and generally start living an extravagant lifestyle. This often comes at the expense of saving for financial goals later in life. The realization that their focus needs to change comes too late, and there isn’t enough time or money available to catch up. Be careful about how you spend your money, especially early in your career.

The pros and cons of buying vs. renting your home

All of the above mistakes are avoidable. If you want to be financially successful, avoiding these mistakes while executing your financial plan is critically important.

Do I need an umbrella insurance policy? If so, how much should I get?

An umbrella insurance policy covers the same things as your home and auto policies, plus some additional items, including lawsuits. Umbrella coverage picks up where the liability limits of your homeowner and auto policies leave off. Most insurers cap the home and auto liability coverage they will sell you at $500,000 or $1 million. If you have assets valued above what your home and auto policy cover, an umbrella policy can cover those assets. Umbrella policies are usually sold in increments of $1 million, so determining an appropriate amount will require that you calculate the value of your assets not covered by your home and auto policy.

The information in this column is designed to be authoritative. The publisher is not engaged in rendering legal, investment, or tax advice.

Procrastination and lack of an investment strategy can jeopardize long-term success.

Avoid these six mistakes that can hinder your financial goals

One of the key elements of successful percutaneous nephrolithotomy (PCNL) surgery is obtaining percutaneous access. In this interview, 

 outlines his step-by-process for obtaining access, discusses the ways he reduces radiation exposure during PCNL, and gives his thoughts on how clinicians can gain proficiency with percutaneous access. Dr. Knudsen is an endourologist, the Henry A. Wise II Endowed Chair in Urology, and Director of the OSU Comprehensive Kidney Stone Program at The Ohio State University Wexner Medical Center, Columbus. Dr. Knudsen was interviewed by 

 the Uehling Professor and founding chairman of urology at the University of Wisconsin, Madison.

Please discuss the principles of percutaneous access.

At The Ohio State University, we do a lot of PCNL procedures and have gone through a series of evolutions over the years. The basic principle is to have precise, clean access into the kidney that permits easy access to the stone(s) and minimizes bleeding. The goal is to enable the clinician to do the case safely and effectively.

When we approach any stone patient, we always study the stone, the kidney, and the anatomy, and create a plan-usually heavily based on the CT scan-of where we’re going to go into the kidney and how we envision that operation going.

In the past, it was pretty straightforward; we did all our access antegrade prone with split-leg spreader bars. Over the years, that has evolved. Our access was always 30F in the past and now, with new options for tract sizes, we rarely utilize 30F PCNL tracts but rather favor smaller tract sizes. It is important to limit the number of punctures into the kidney to reduce the risk of bleeding and other complications, so we always try to make the first puncture as accurately as possible. If you can get it on the first shot that’s generally going to be your best opportunity. Once you have the puncture in the right spot then it is a matter of simply dilating the tract and removing the stone. With a good puncture, usually the rest of the case is fairly straightforward.

Take us step by step through obtaining percutaneous access on a procedure, beginning with looking at the CT scan.

When we see a patient and make the decision to proceed with a PCNL, we’ll look at the imaging. Is the stone in the upper pole? Is it in the lower pole? Is it in the pelvis? Are there multiple stones?

Holmium, thulium lasers show similar ablative effect on stones

Some surgeons prefer to go in a certain location for all cases, such as the upper pole. This is not our approach. Our approach is to pick the best calyx to get to the target. If lower pole is going to give us the best shot for a lower pole stone, that’s where we’ll go. If upper pole is better, then that is where we will go provided the CT does not show any other anatomic problems with an upper pole approach.

You have to look at the pleura and you have to look at the spleen and liver and make sure that they’re not going to be in a problem with your choice of tract location. That’s where getting the CT scan is very valuable.

Once we pick the location of the tract, the other thing we think about is the size of the tract. That is really a function of the stone. If it’s a smaller stone-1.5 to 2 cm in size-we’re probably going to do a mini on that patient. If it’s a single stone, we’re going to lean toward a mini, even if it’s a little bit bigger. If there are multiple stones scattered through the kidney or if it’s a very large stone or branching stone, then we’re probably going to do a larger tract. But for us now, a large tract is 24F rather than 30F.

"There are a lot of simple things that can be done to reduce the amount of radiation"

Please discuss radiation exposure with regard to PCNL.

That’s something we’ve been very concerned about, not only for our patients but also for the surgeon and the staff in the operating room who are there every day doing multiple cases. We actually recently published a paper on reducing radiation during PCNL by looking at certain steps of the procedure and the ways we can reduce it 

Emergent setting linked to lost follow-up for stents

There are a lot of simple things that can be done to reduce the amount of radiation. Number one is just being aware of radiation: alerting the staff, alerting your residents, having a discussion with your x-ray technologist in the room. All of these are important. There are other simple steps to take: using a low dose mode on the C-arm, using pulse modes, coning-down and collimating the C-arm image, use last image hold, using spot rather than continuous imaging, and employing a foot pedal will all reduce the amount of radiation exposure. We have been able to reduce fluoroscopy use to under a minute in many cases by employing these simple steps.

There’s no question that incorporating ultrasound can bring down your radiation as well. There are some barriers to learning ultrasound; it depends on your comfort level with it and also on your patient population as obesity can increase the challenge of ultrasound. However, it is now something that we are currently employing during all our PCNL procedures. We will visualize the kidney and determine if we are comfortable proceeding with an ultrasound guided puncture. We still have the C-arm on hand and often use it to check things if we are not certain with ultrasound alone. This “hybrid” approach is a great way to become more comfortable with ultrasound.

What are the pitfalls and complications of percutaneous access?

Surgeons do worry about complications from PCNL, and when you look at some of the most devastating complications, bleeding is right at the top of the list. The more sticks you have into the kidney with a needle, the more opportunity there is for bleeding. By being competent at gaining access effectively, you can reduce that risk. Remember to always try and make the first puncture as accurately as possible.

How would you counsel the patient on their risks before a given procedure?

I walk every patient through the surgery. I explain that we are going to create the tract at the time of the operation and that I need to get up into the kidney through a tract to do the operation. I would say we are 99% successful at getting access.

I don’t spend a lot of time telling them that I don’t expect to be successful unless there is some complicating factor such as an altered anatomy, but in a normal, routine patient, access usually isn’t the problem. I quote them about a 1% risk of major bleeding requiring transfusion and possible embolization, and that’s been our consistent experience over many years at our center. I tell them we are not planning to transfuse them; we are not going to group and match them for blood. We don’t do that routinely. I do counsel them on the risks of delayed bleeding when they go home and that if they do have bleeding, they need to come back and alert me.

What type of drainage do you use post-stone removal?

It depends, but we have moved away from nephrostomy tubes for the most part. We will only use nephrostomy tubes if we believe we need to go back in percutaneously, such as for a planned second-look nephroscopy or a staged procedure, on that patient. If the patient absolutely does not want a stent under any circumstances, then we might also leave a nephrostomy tube after the procedure.

How to bill when a stone changes location during procedure

We’ll leave stents in the majority of patients, but we’ll often leave them on a string exiting via the urethra and take them out the next morning. A lot of times, we’re stenting just overnight and monitoring for bleeding and/or fevers. If the patient is stable in the morning, the stent comes out before discharge. If there are issues, then we simply leave the stent in longer. With mini-PCNL procedures, and occasionally 24F procedures, we will do them totally tubeless with no stent at times, usually when there is very little bleeding and no edema around the ureteropelvic junction.

Do you put the stent in in the prone split-leg position?

You certainly can, both antegrade or retrograde. We did this for many years. However, we have now moved to doing about 80% of our PCNLs in the supine position. Supine also facilitates both antegrade or retrograde stent placement. When we place them retrograde, we watch the coil in the kidney deploy with the nephroscope, thereby reducing the use of fluoroscopy.

"You need that critical volume of cases once you start"

As you know, a minority of urologists do percutaneous stone removal. Do you think you need a fellowship to do this?

You don’t need a fellowship, but there are a couple of important things that need to happen. One is you must get the training in your residency if you’re not going to do it in a fellowship. There are a lot of residencies where the residents come out quite competent to do their access. At Ohio State, our residents graduate being able to do access and this is certainly the case for other programs as well.

Age a predictor of filling opiate prescriptions post-URS

Then, you need that critical volume of cases once you start. That’s been a little bit of a barrier for some individuals where they didn’t have the volume when they started their practices. In this situation, you can lose your skills and/or confidence pretty quickly and then give up doing the procedure altogether. I suspect this happens a lot.

How many cases do you think you need to do to be trained, and then how many cases per year do you need to do to keep up?

There have been a few studies that have looked at learning curves, but I would say 20 to 30 cases in a 1-year period to be trained. You’re going to need probably about 20 cases a year to maintain skills in the future. That being said, learning is a lifelong endeavor; even today after more than a thousand procedures, I feel there is always something new to learn, to optimize, and to make the procedure better. This is why performing PCNLs is such a rewarding experience.

Do you believe that urologists should do all access?

There are different models that work. The key is, if you aren’t doing the access yourself, then working with someone who understands the surgery and the goals of the operation is very important. If you and your radiologist work together and plan the tract together, that’s a perfectly fine and very reasonable approach. Certainly, the model of having a radiologist that you work with closely can be very successful and may help you through that learning curve too.

The challenge is if somebody has a nephrostomy tube put in by a radiologist whose only concern is getting a tract in somewhere and is not focused on the best location for the stone, then it can lead to problems later. We will also often see patients who had nephrostomy tubes placed urgently, such as when they present with sepsis from an obstructing stone. After the initial infection is treated and the patient is stabilized, then we will take them to the operating room for the PCNL. Our experience is that the location of the tracts from the urgent nephrostomy tube placement are rarely adequate for the procedure. However, the tracts facilitates performing an antegrade nephrostogram and then permitting us to choose a location for a new tract in the OR.

You mentioned you’ve made the transition to supine. How do you keep current in the field?

You have to be open to new ideas. For any surgeon, it’s important to not get too comfortable with what you’re doing, even if it’s going well. You need to keep an open mind and think about how you can make things even better than what you’re doing. Meetings and training courses-those from the AUA are a great example-are great places to pick up new ideas and learn. Just getting together with your colleagues and discussing your approach is a very valuable way to understand why you might want to think about doing things differently. While I felt perfectly comfortable doing procedures prone, I decided to try supine based on feedback from others. I also had experience doing retrograde PCNLs as a resident, and the supine position was not that much different. As I embarked on supine, I felt it facilitated the mini-PCNL approach since the tract was more dependent and the stones washed out easier with the Venturia effect. Unsurprisingly, our use of mini-PCNL continues to grow. Having more tools in the tool chest is always valuable.

How would you recommend that someone learn PCNL access and PCNL if they’re already done with their training?

There are some good training courses now. The AUA sponsors a pretty robust training course on percutaneous access that’s run multiple times a year. There are centers that do a lot of PCNLs where you can gain that expertise from a visit. We are always open to having visitors at OSU to see procedures. For residents who are interested in endourology, there are many very good fellowship programs including our program at OSU. Once in practice, having a surgeon with you in the OR who is an expert in access look over your shoulder for a few cases may also be beneficial. You can also partner with somebody at your own institution if you have a colleague who has some expertise with this.

In this interview, Bodo Knudsen, MD, outlines his step-by-process for obtaining percutaneous access, discusses the ways he reduces radiation exposure during percutaneous nephrolithotomy, and gives his thoughts on how clinicians can gain proficiency with access.

Percutaneous access: Principles and best practices

The high-power holmium (HPH) laser with Moses technology (Lumenis Moses Pulse 120H) and the super-pulse thulium fiber laser (SPTF) have a similar ablative effect when operated at the same power, but when evaluated at maximal dusting settings, the SPTF laser seems to hold an advantage for greater efficiency, according to research reported at the AUA annual meeting in Chicago.

Researchers compared the ablative effects of the two laser systems in an in vitro study using calcium oxalate monohydrate-like artificial stones and a prototype of the SPTF laser.

“Innovations in lithotripsy technologies continue to emerge. The Moses technology was developed to enhance the HPH laser lithotripter, but more recently it is being challenged by the novel SPTF laser that features a more optimal wavelength with a higher water absorption, lower pulse energy, and higher pulse rate (frequency),” said first author Laurian B. Dragos, MD, consultant urologist at Victor Babes¸ University of Medicine and Pharmacy, Timis¸oara, Romania.

“Our study shows that the SPTF laser might increase the efficiency of laser lithotripsy, therefore decreasing operative time. Still, we need to consider that these are in vitro findings, and our study did not assess other aspects of laser lithotripsy such as retropulsion, visibility, and size of the resulting stone fragments (dust). Further clinical evaluations are required.”

The in vitro study analyzed ablation volumes created in calcium oxalate monohydrate-like artificial stones using the two laser systems. The HPH laser was equipped with a 230-micron core-diameter fiber, and the SPTF laser, which was a prototype device, had a 200-micron core-diameter fiber. The SPTF laser can use fibers as small as 50 microns.

Each laser was used in several different experimental setups that used a variety of settings for power, energy, and frequency and distances of 0, 1, and 2 mm between the laser fiber and the stone. For each combination of settings, the tests with the HPH laser were done in both close and distance modes. Time of laser activation was 10 seconds in all experiments.

Ablation volume was measured using a 3-D high-precision computer-controlled micro-scanner.

For both laser systems, ablation volume increased with increasing laser power and decreased as the distance between the fiber and the stone increased. Results achieved using the HPH Moses technology laser in distance and close modes showed that if power, energy, and frequency were kept constant, ablation volume was consistently greater when the laser was operated in distance mode. The differences between the two modes, however, were not statistically significant.

The ablation volumes achieved using the SPTF laser were similar to those achieved using the HPH Moses technology laser in distance mode when the two devices were operated with the same power and pulse energy settings. The two technologies also resulted in similar ablation volumes when they were operated with the same power and the HPH Moses technology was used in close mode with a very low pulse energy and very high frequency.

At each laser’s best capabilities for dusting settings that used the lowest pulse energy and highest frequency (HPH: 0.2 J and 80 Hz; SPTF: 0.05 J and 900 Hz), the ablation volume was almost threefold greater for the SPTF laser than for the HPH Moses technology laser. At stone distances of 0 mm and 1 mm, mean ablation volume was 1.28 mm

, respectively, for the SPTF laser; 0.42 mm

, respectively, for the HPH laser in close mode; and 0.48 mm

, respectively, for the HPH laser in distance mode.

The high-power holmium laser with Moses technology (Lumenis Moses Pulse 120H) and the super-pulse thulium fiber laser (SPTF) have a similar ablative effect when operated at the same power, but when evaluated at maximal dusting settings, the SPTF laser seems to hold an advantage for greater efficiency, according to research reported at the AUA annual meeting in Chicago.

Vol. 47 No. 7

Novel US ablation therapy shows significant PSA effect

Avoid these six mistakes that can hinder your financial goals

Percutaneous access: Principles and best practices

Holmium, thulium lasers show similar ablative effect on stones