Keith Loria is a contributing writer to Medical Economics.

Keith Loria

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The usual approach to cancer treatment is to act fast and use some combination of surgery (if it is a solid, operable tumor), radiation and chemotherapy to get rid of as much of the cancer as possible.

But for many men with localized, low-grade prostate cancer, the best course seems to be active surveillance: closely monitoring the disease and putting off treatment until the cancer progresses. Active surveillance for prostate cancer is firmly in the mainstream of cancer treatment. The National Comprehensive Cancer Network (NCCN) and other groups have guidelines that say it is the preferred option for many men with localized, low-grade prostate cancer. Research reported last year in 

 showed that the proportion of men with localized, low-grade prostate cancer who chose active surveillance or watchful waiting increased from 14.5% in 2010 to 42% in 2015. Watchful waiting is now commonly understood to mean monitoring the cancer but with no intention to treat it because of the patient’s age or poor health.

Active surveillance is commonly used to manage prostate cancer, because localized prostate cancer is often slow growing, is unlikely to metastasize and doesn’t cause symptoms. But physicians and patients take the same approach with some other similarly “indolent” cancers. The American Thyroid Association guidelines, for example, recommend active surveillance as an option for people with low-risk papillary thyroid cancer. Sometimes active surveillance is a strategy used after initial treatment — for example, it’s an option for men with early-stage testicular cancer who have had orchiectomy (surgery to remove one or both testicles).

As accepted as active surveillance has become, it still involves many gray areas and judgment calls. Is it an option for men whose prostate cancer is in the intermediate-risk category? The particulars of germline gene testing — which men should get it and which genes should be tested for — are still being hashed out. Research has shown that mutations in the BRCA1 and BRCA2 genes, plus a few others, are associated with aggressive, possibly lethal prostate cancer. The NCCN guidelines recommend germline testing for men with low- and intermediate-risk prostate cancer if they have a family history of inherited cancer or certain histologic findings. There is also the question of what exactly active surveillance should entail. Until fairly recently, men underwent invasive biopsies if rising PSA levels or abnormalities detected with a digital rectal exam suggested that their prostate cancer might be growing. Now it is an open question whether an MRI imaging, at least in some situations, might replace biopsies as a way of detecting the disease.

Regardless of the updates, active surveillance is fundamentally a wait-and-see approach to cancer. “It is a way of monitoring prostate cancer that isn’t causing any symptoms or problems,” says Ronald Tutrone Jr., M.D., FACS, of Chesapeake Urology in Baltimore.

Active surveillance of prostate cancer emerged as a strategy partly because widespread screening for the disease with PSA tests resulted in many more early cases being discovered. The U. S. Preventive Services Task Force and other groups have adjusted their screening recommendations, but there is still plenty of screening and early detection occurring.

“We find the cancer when it’s early and low risk,” notes Dan Sperling, M.D., DABR, medical director and founder of the Sperling Prostate Center in Florida and New York. The average age of diagnosis is dropping, and “younger men with low-risk prostate cancer do not want to risk the urinary and sexual side effects of whole-gland treatments like surgery and radiation,” adds Sperling. His center’s website says that Sperling specializes in MRI imaging and that he has developed a special technique called BlueLaser 3T mpMRI.

Sperling points to research results published in the July issue of the 

 as evidence for the wisdom of active surveillance. The study included 2,664 men who were managed with active surveillance at Memorial Sloan Kettering Cancer Center in New York City. The treatment-free probability at 5, 10 and 15 years was 76%, 64% and 58%, respectively, and the risk of distant metastasis was 0.6% at 10 years.

Men often improve their health habits after a prostate cancer diagnosis in hopes of lowering the risk of the cancer growing and metastasizing. There is no guarantee, of course, that the changes will affect the course of their cancer, but the men who make them wind up looking and feeling better, according to Sperling: “Some men on active surveillance say that getting a prostate cancer diagnosis was one of the best things that could have happened.”

Nitesh Paryani, M.D., founder and medical director of Tampa Oncology and Proton, says that over the last decade, oncologists have learned that perhaps not all prostate cancer patients require treatment and that active surveillance can spare some men from the risk of treatment side effects, which include erectile dysfunction and urinary problems. But as Paryani notes, active surveillance is not without its risks. Repeat biopsies can also lead to erectile dysfunction and other problems. “Many patients opt not to pursue active surveillance due to this,” says Paryani, adding that the “anxiety of having a cancer diagnosis often plays a role as well.”

Ardeshir Rastinehad, D.O., vice chair of urology at Lenox Hill Hospital in New York City and director of prostate cancer at the Northwell Health, a New York metro area health system, says that “watchful waiting” is more accepted today because of biomarkers, MRI scans and “fusion biopsies” that allow clinicians to use MRI scans to guide biopsies: “Imaging, biomarkers and genomics are helping us pick the right patients that need treatment and the others that we can follow and, hopefully, will never be affected by prostate cancer and can avoid the effects of treatment,” says Rastinehead.

Tutrone of Chesapeake Urology recently treated Baseball Hall of Famer Cal Ripken Jr., who received a diagnosis of prostate cancer earlier this year (Ripken was treated surgically and has told reporters the treatment was successful). Tutrone recommended a liquid biopsy test called the ExoDx Prostate Test. The developers of the urine-based test, which measures exosomal RNA associated with the presence of prostate cancer, say that it is a better indicator of prostate cancer risk than the conventional PSA test and therefore might help some men avoid unnecessary biopsies.

A study published in May 2020 showed that the ExoDx Prostate Test can influence clinician and patient behavior. Conducted in collaboration with CareFirst Blue Cross Blue Shield, a Blues plan in the Maryland; Washington, D.C.,; and Northern Virginia market, this study included more than 1,000 patients and about 70 urologists. When the results of the ExoDx Prostate Test were used and evaluated in a clinical setting, 92% of patients followed the physician’s recommendation to defer having a prostate biopsy. “Payers really like it when patients follow physician recommendations,” Tutrone says. “And early detection of prostate cancer is key to saving lives and reducing costs over time.” The test was also associated with the discovery of more high-grade prostate cancers.

Rastinehad at Lenox Hill Hospital says that a “middle way” between active surveillance and treatment, called focal therapy, is being studied. Focal therapy zeroes in on small tumors in the prostate but leaves the rest of the gland intact. “In patients that are not great candidates for active surveillance but have disease we can see on MRI, we may be able to treat just the abnormal spot and keep men from having those unwanted side effects of surgery and radiation while still trying to achieve cancer control,” he says.

®, is a freelance writer in the Washington, D.C., area.

Articles

Prostate cancer is often “indolent,” so it can be monitored and not treated right away. 

Active surveillance: Men, clinicians are taking a wait-and-see approach to prostate cancer

The American Society of Hematology (ASH) will present its annual meeting and exposition virtually Dec. 5-8. Even though the meeting is not happening in person, attendees will still have the opportunity to review thousands of scientific abstracts dealing with the buzziest news and most talked-about topics in hematology today.

Robert A. Brodsky, M.D., ASH secretary and director of hematology at Johns Hopkins University School of Medicine in Baltimore, says the topics will include advances in areas including gene therapy, genome editing, bone marrow transplantation and hematologic malignancies, and a lot of basic research involving stem cells, leukemia progression and immunology.

As for the latest in drug treatments in the pipeline, Brodsky believes two large phase 3 trials will likely garner the most interest.

“The first is the APOLLO trial, a phase 3 randomized study of subcutaneous daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone,” he says, referring to a closely watched trial of treatments for multiple myeloma. “There is also the REACH3, a phase 3 randomized study of ruxolitinib versus best-available-therapy,” says Brodsky, referring to a chronic graft-versus-host-disease (GvHD) trial.

David Feltquate, M.D., Ph.D., global head of Novartis’ hematology disease unit, notes that chronic graft-versus-host disease is a common and very serious complication of allogeneic (from one person to another ) stem cell transplantation, and patients frequently become resistant or dependent on steroids. GvHD occurs when the new T cells generated by the stem cell transplant recognize the recipient’s cells as “foreign” and mount an immunological attack. The skin, gut and liver are most commonly affected. Estimates of how common GvHD occurs vary greatly, and the risk of occurrence depends, in part, on the degree of tissue compatibility between the donor and the recipient. GvHD is conventionally divided into the acute form, which occurs within 100 days of the stem cell transplant, and the chronic one that occurs afterward. The condition can have major effect on people’s quality of life and serious cases can be deadly.

“This is why we are so excited about the results of REACH3, a phase 3 study that looked at Jakavi (ruxolitinib) in patients with steroid-refractory or steroid-dependent chronic GvHD,” he says. “What we know now is that Jakavi met the primary endpoint of the study, defined as superior overall response rate after 24 weeks, compared to best available therapy. We also know that Jakavi met two very important secondary endpoints, which were improvements in failure-free survival and also patient-reported symptoms.”

Jakavi is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases approved in Europe as a treatment for adult patients with polycythemia vera (PV) who are resistant to, or intolerant of, hydroxyurea, and for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (MF), post-polycythemia vera MF or post-essential thrombocythemia MF. Novartis licensed ruxolitinib from Incyte Corp. for development and commercialization outside the United States. The drug is marketed in the United States by Incyte as Jakafi.

The REACH3 trial has forerunner, REACH2, which was designed to study Jakavi in people with the acute form of GvHD. The REACH2 results were published in the May 7, 2020, issue of 

. The investigators randomized 309 acute GvHD patients for whom glucocorticoids were not effective (“glucocorticoid-refractory”), 154 to Jakavi and 155 to a control group that was treated with a therapy chosen by the investigator from list of nine options (the large number of choices is indicative of just how unsettled treatment of GvHD is). The primary endpoint was overall response 28 days after the treatment started. The results showed that 62% of the patients in the Jakavi group met that end point compared with 39% of those in control group. The patients on Jakavi also fared better on various other endpoints.

“This is a major improvement in outcomes for acute GvHD patients and taken together with the results seen in chronic GvHD, could mean a change to standard of care for a very difficult-to-treat disease,” Feltquate says. “Based on these data, we plan to file for marketing authorization in GvHD in Europe and other countries.”

The full data from the REACH3 study is expected to be presented at a medical meeting in early 2021.

“Jakavi is now the first treatment to demonstrate efficacy in a large-scale randomized clinical trial in steroid-refractory or steroid-dependent chronic GvHD,” Feltquate says. “This is potentially practice-changing news in a disease area where unmet need and patient impact are very high.”

In the phase 3 APOLLO randomized study comparing subcutaneous Darzalex (daratumumab) in combination with (Pomalyst) pomalidomide and dexamethasone compared with Pomalyst and dexamethasone alone in relapsed or refractory multiple myeloma, the daratumumab combination met the primary endpoint of improving progression-free survival.

“We are pleased with these positive results for daratumumab, administered as a subcutaneous formulation, in combination with pomalidomide and dexamethasone,” Jan van de Winkel, Ph.D., CEO of Genmab, said in a company press release issued in late July. Janssen bought the development and marketing rights to Darzalex in 2012.

As a phase 3 trial of treatment of a blood cancer with an increasing incidence in some populations, the APOLLO trial is noteworthy, but the results won’t break new ground. The FDA approved the Darzalex-Pomalyst-dexamethasone combination three years ago based on favorable results from a single-arm, phase 1 study. And in August of this year, the FDA approved another “triplet therapy” for relapsed or refractory multiple myeloma that includes Darzalex, Kyprolis (carfilzomib) and dexamethasone.

In addition to the APOLLO and REACH3 trial results, Brodsky says the ASH schedule includes presentation of results from a multicenter trial comparing reduced-intensity allogeneic hematopoietic cell transplantation to hypomethylating therapy or best supportive care.

“It shows an important survival advantage in older patients with advanced myelodysplastic syndrome,” he says. “This will be the new standard of care.”

Another notable area of research is bone marrow transplant, including markedly expanded access to this potentially curative therapy with haploidentical donors, says Brodsky, who also foresees discussion about new research into sickle cell disease during the ASH meeting.

“There are exciting data in curative intent therapies,” he says. “Haploidentical bone marrow transplant results continue to be outstanding. Cure rates are approaching 90%. There are gene therapy and editing approaches showing encouraging early data in small numbers of patients. And there is exciting data for fixed-dose hydroxyurea in Africa.”

®, is freelance writer in the Washington, D.C., area.

Results of APOLLO and REACH3 trials are scheduled for presentation at the American Society of Hematology meeting next month are expected to garner attention.

Positive results for Darzalex, Jakavi to be reported at ASH 

The COVID-19 pandemic has been a bumpy ride in the United States, featuring one controversy after another. One of the few areas of agreement is that the widespread adoption of telehealth amid the pandemic has been, by and large, a positive development.

Here are the remaining 5 takeaways about the telehealth boom.

6. Telehealth has a role in inpatient care

Doctors attending to patients who are at home has fueled the COVID-19 telehealth boom, but telehealth is also playing a role in inpatient care. “During [the pandemic], we also found ways to implement telehealth among our inpatients in the hospital,” Pageler says. “This allowed physicians to care for patients in isolation while minimizing the spread of infection and conserving personal protective equipment, such as masks and gowns.”

Antall says many overwhelmed hospitals have had to “beam in” specialists from parts of the country with fewer COVID-19 cases. “We also saw telehealth as an important way for the ‘worried well’ to see a doctor from the comfort of their home so they didn’t have to take up critical space in emergency rooms if not necessary,” he says.

Northwell Health uses two telehealth platforms that involve some inpatient care, according to Berman: eICU, which utilizes Philips eCareManager software and consists of hardwired beds in ICUs that contain high-definition cameras, speakers, a monitor and a button that if pressed calls directly into a remote critical care team located in a command center that can supplement the bedside direct care team 24/7; and DTC (direct to consumer), which is being used for home televisits, clinic-to-clinic and consultations to the ER, and floor care of the hospitals.

7. Telehealth could widen, deepen the digital divide

Could the current go-go attitude about telehealth be going too far? There are some skeptics who argue that some nuanced information and connection is lost for lack of in-person care.

Emphasizing telehealth may deepen a digital divide that those with access to Wi-Fi, broadband, and fast, smart devices don’t experience and therefore may underestimate. According to the Federal Trade Commission, 19 million Americans lack access to fixed broadband service at threshold speeds, a problem much more acute in rural areas. Pew Research found that 19% of Americans do not own a smartphone. And there’s the irony that many of those without access to broadband or a smartphone are the very people who might benefit the most from telehealth because of access, mobility, and transportation issues.

“One trend we must be cautious of as this evolves is that we do not leave other at-risk populations behind—those who do not have adequate broadband coverage or access to devices either because of cost or location,” Berman says. “If we solve for that, we are on our way to a very new world of health care.”

8. Fraudsters see a telehealth opening — and take it

Almost every boom presents an opportunity for fraud, and the telehealth boom is no exception, In late September, the Justice Department announced it had charged 86 people with submitting $4.5 billion in fraudulent claims related to telemedicine. According to a press release about the charges, the defendants are accused of paying doctors and nurses to order unnecessary durable medical equipment, genetic and other kinds of diagnostic testing, and pain medication. The Justice Department press release also said that apart from the criminal cases, the CMS Center for Program Integrity had revoked the Medicare billing privileges of 256 medical professionals because of their involvement in telemedicine schemes.

9. State licensing requirements could become an obstacle

As the COVID-19 pandemic escalated in the spring and the demand for telehealth became apparent, many states moved to relax licensing rules that allowed healthcare professionals from other states to provide telehealth services. Those changes were another key ingredient in the telehealth boom recipe. But in some cases, the licensing rules were relaxed on a temporary basis and they might be tightened up if and when the COVID-19 pandemic eases up.

“For pediatric care especially, where specialists are often few and far between, we need to advocate for those state licensing changes to remain,” Pageler says.

10. Telehealth, in-person: Tis not an either/or

The course of the COVID-19 pandemic over the next several months is difficult to predict with any certainty. There are too many variables, including but not limited to the availability of a vaccine, adherence to social distancing and mask wearing, treatment advances, and the consequences of the election. But there has been resumption of some in-person care and indications that the demand for telehealth has slackened relative to the zenith in April and May when remote care was essentially the only option short of an outright emergency or absolute necessity.

“There are always going to be people who prefer to get their care in person, and there are always going to be some scenarios for which in-person care is better,” Antall says. His company believes in a hybrid-care model that offers support whether patients receive virtual or in-person care. “We want this to be a seamless experience,” Antall says.

, is a healthcare writer in the Washington, D.C., area.

The second of a two-part story on 10 takeaways about the telehealth boom. The COVID-19 pandemic has been a bumpy ride in the U.S., featuring one controversy after another. One of the few areas of agreement is that the widespread adoption of telehealth amid the pandemic has been, by and large, a positive development. 


5 More Takeaways About the Telehealth Boom

Here are the first 5 takeaways about the telehealth boom.

1. It wouldn’t have happened without CMS loosening its rules and paying for it

Earlier this year, CMS enacted new rules to provide practices with the flexibility to use telehealth solutions in response to COVID-19. They included providing payment parity for telehealth visits, allowing payment for many codes that were previously considered nonpayable, and the willingness of the federal Office for Civil Rights to waive enforcement of the HIPAA privacy rules allowing the use of non-HIPAA compliant technologies like FaceTime and Zoom to conduct visits.

“The COVID-19 pandemic led to a quantum leap in moving telehealth forward, almost overnight,” says Ronald Hirsch, M.D., FACP, vice president of regulations and education for physician advisory solutions at R1 RCM, a revenue cycle management company in Chicago. “However, this would not have happened without the regulatory flexibilities provided by CMS and other payers.”

In October, CMS announced it will reimburse providers for 11 more telehealth services, bringing the total to more than 140. Its proposed 2021 Physician Fee Schedule also paves the way for greater use of telehealth and would make some changes permanent instead of being tied to the federal government’s January 31 declaration of a public health emergency.

Of course, there was telehealth before the pandemic. It was gaining a foothold in many areas of the healthcare system but it seemed stuck on the margins, particularly among large health systems on the East Coast.

“The slow adoption was largely due to the lack of reimbursement and payment parity when there was reimbursement all,” says Iris Berman, M.S.N., RN, vice president of telehealth services at Northwell Health, the 23-hospital health system in the New York metropolitan area. “Much of the reimbursement directed by CMS was to rural communities, which excluded many of our most vulnerable in urban population centers.”

2. There’s no going back partly because telehealth has become so

Peter Antall, M.D., chief medical officer of Amwell, a Google-backed telemedicine provider that went public in September, says the average monthly visit volume on his company’s platform increased by about 300% between April and June compared with the first three months of the year.

“Today telehealth is no longer a nice-to-have but rather seen as necessary part of the care journey, and we expect this momentum to largely continue post-pandemic,” Antall says. “Ultimately, you can’t put the toothpaste back in the tube. Now that both patients and providers have experienced the convenience of telehealth, we don’t anticipate healthcare to ever go back to how it was.”

Adoption and acceptance grew as both the public and the providers realized gains such as improved scheduling, reduced travel time, and easier access to specialists, which sometimes occurred in a matter of minutes or hours instead of days and weeks. “Time will tell what the future holds for telehealth but we won’t return to the baseline we were at before the pandemic,” says Natalie Pageler, M.D., M.Ed., chief medical information officer at Stanford Children’s Health and clinical professor of pediatric critical care at Stanford University. “Now that both patients and physicians have tried it and learned how to use it, they see the value and incentive to continue using virtual visits.”

Before the pandemic, Stanford Children’s Health was conducting about 20 telehealth visits per day in the ambulatory setting. Within a matter of weeks, that number grew to 700 to 800 per day. “In May, we began resuming care that had been delayed by COVID-19. But even now as our in-person visits are continuing to increase further, we’re still seeing almost the same number of telehealth visits,” Pageler says. “With the increase in awareness of the capabilities of telehealth and digital health, we are seeing many lessons learned from both the provider perspective as well as the patient/family perspective about the value of telehealth visits and the type of care that can be delivered via telehealth.”

George Valentine, a telehealth executive at Cox Communications, a regional telecommunications company headquartered in Atlanta, Georgia, shares the opinion that telehealth is winning the popularity contest. Valentine pointed to survey data collected by consulting company McKinsey & Co. that found that 74% of telehealth users reported high satisfaction, that 57% of providers view telehealth more favorably than they once did, and that 64% of providers are more comfortable using it now than ever.

Once COVID-19 arrived, the slow-and-steady-wins-the-race pace turned into a sprint. Healthcare providers started working around the clock to start telehealth programs and improve connectivity. Part of the motivation was making up for revenue lost by the lack of office visits.

Forrester Research issued a report in October that made bullish predictions for telehealth next year. The report noted the sharp drop-off in primary care visits because of the COVID-19 pandemic and the rise of telehealth (and the health clinics inside retailers) to take their place.

“Primary care as we know it today stands in the crosshairs, with new entrants vying for the hearts of consumers who legacy healthcare ignored for too long,” said a Forrester blog post about the report.

Millennials and their demographic successors in Generation Z have grown up in immersed in an online, digital environment. It has been a truism of telehealth that it would appeal most to younger people who are used to conducting so much of life remotely via their phones and other devices. But recent surveys have shown that age may be less of a factor in telehealth acceptance than many thought, and that those older than 65 have seen the value and convenience of using telehealth services.

“Used correctly, it is an adjunct to in-office visits that saves time in travel and can actually improve coordination of care,” Berman says. That could be especially important for older people because they are more likely to have multiple and complex health problems. In the past, people with complex medical problems would have to make separate trips to see, say, their pulmonologist, cardiologist and oncologist. Each of these visits required arranging transportation and carving out several hours out of the day. Telehealth will not replace the in-person visits if only because of the tests that must be done in person; the tele-MRI scan is not available yet. Still, with telehealth, it is conceivable that separate specialists could be convened for the same patient visit and the care coordination that is much talked about but realized much less often might actually occur.

About 80% of visits are about seeing and talking with patients, sometimes with significant others present, with no physical presence required, Berman notes. “Using telehealth for these types of visits affords more efficiency and less wait time in offices for the patient,” Berman says. “Provider quality of life can improve as well. All of this, of course, is with appropriate and well-planned use in conjunction with good workflows. We must think about telehealth as being a tool in the tool chest.”

5. But telehealth could be boon for pediatric care, too

Pediatrics requires some in-person care; a vaccine can’t be administered digitally. And typically children are not dealing with chronic conditions that require medication, tests and so on. Still, childhood is a period of relatively high use of healthcare services, some of which might improve with telehealth. Pageler says telehealth could be important for child health because it allows some services to be provided without disrupting school, sports, and other extracurricular schedules. Unless the condition warrants intensive hospital care or specific in-person procedures or exams, telehealth would allow physicians to see patients who require ongoing care for follow-up appointments, she says.

The first of a two-part story on 10 takeaways about the telehealth boom. The COVID-19 pandemic has been a bumpy ride in the U.S., featuring one controversy after another. One of the few areas of agreement is that the widespread adoption of telehealth amid the pandemic has been, by and large, a positive development. 


Keith Loria

Articles

Active surveillance: Men, clinicians are taking a wait-and-see approach to prostate cancer

Positive results for Darzalex, Jakavi to be reported at ASH

5 More Takeaways About the Telehealth Boom

5 Takeaways About the Telehealth Boom