Leah Lawrence

When Jason Midkiff, 46, was diagnosed with testicular cancer 20 years ago, he was not concerned about whether he could have children in the future.

“I was pretty focused on my career and didn’t have a significant other at the time,” Midkiff recalls. “I think of myself as having been young, dumb and foolish.”

To be fair, Midkiff was facing an aggressive form of testicular cancer called pure embryonal carcinoma. Testicular cancer is subdivided into seminoma and non-seminomas, with embryonal carcinoma falling in the non-seminoma category. Embryonal carcinoma, which occurs in about 3% to 4% of testicular cancers, according to the American Cancer Society, tends to grow rapidly and spread outside the testicle.

Jason Midkiff was not focused on having children when he received a diagnosis of testicular cancer.

Midkiff first noticed some swelling in one of his testicles at age 26. Swelling is a common symptom of testicular cancer but can be due to multiple causes. Midkiff’s primary care physician initially treated him for inflammation before ultimately recommending he undergo an ultrasound.

The ultrasound revealed a mass, and Midkiff was referred to a urologist for a biopsy.

“I had a surgery to remove the mass and was scheduled to undergo a second surgery to remove some of the lymph nodes in my groin,” Midkiff says.

His urologist initiated a conversation about possible infertility prior to his second surgery. Unfortunately, Midkiff says, he figured it would not be a big deal for him.

Today, a father to five adopted children, Midkiff says he is not sure he would do anything differently.

“Hindsight can be tough,” he says. “But I can’t imagine my life without the kids I adopted.”

A testicular tumor is a space-occupying lesion in the testicle that will destroy some of the sperm-producing tissue in that space and consequently decrease sperm production, explains Dr. Larry I. Lipshultz, a professor of urology and chief of the Scott Department of Urology’s Division of Male Reproductive Medicine and Surgery at Baylor College of Medicine in Houston.

In fact, studies have shown that 30% to 50% of men diagnosed with testicular cancer have low sperm counts or dysfunction of available sperm at diagnosis.

“Testicular cancers can also produce certain hormones, such as human chorionic gonadotropin (HCG), alpha-fetoprotein or lactate dehydrogenase, that can upset the endocrine system and disrupt normal sperm production,” Lipshultz says.

The standard of care for treating testicular cancer is radical orchiectomy — removal of the entire affected testicle.

“Almost right away, men with testicular cancer are down one sperm-producing unit,” says Dr. Sarah Vij, a male infertility and andrology specialist at Cleveland Clinic. “Additionally, many men who have testicular cancer will require additional therapy like chemotherapy or radiation to the remaining testicle.”

Men treated with orchiectomy alone have the lowest risk of long-term fertility concerns, Vij says.

Some men, like Midkiff, may require retroperitoneal lymph node dissection to remove the retroperitoneal lymph nodes, where testicular cancer often spreads first. In some cases, this surgery can affect the nerve bundles that control the way semen exits the body, causing retrograde ejaculation, explains Dr. Matthew T. Campbell, an assistant professor of genitourinary medical oncology at The University of Texas MD Anderson Cancer Center in Houston. During retrograde ejaculation, semen flows back into the man’s bladder instead of out through the penis, resulting in infertility.

In addition, chemotherapy and radiation can be toxic to spermatogenesis — the sperm-producing process. The chemotherapy drugs used to treat testicular cancer including cisplatin and ifosfamide tend to be the most toxic to the testicles, Campbell says.

“Chemotherapy agents are a standard of care for men with metastatic testicular cancer or used to prevent the recurrence of testicular cancer, and while they can contribute to infertility, not all men who receive (this treatment) will have lifelong infertility,” Campbell says.

“Another important piece of the puzzle is that treatment with orchiectomy, and later with chemotherapy, can cause low testosterone levels,” Campbell adds. “Low testosterone can impact fertility by affecting a man’s sex drive, causing erectile dysfunction, and reduce production of sperm.”

In addition to the cancer and its treatments, other traditional risk factors such as age, smoking, alcohol use and obesity are associated with infertility in men.

At the time of diagnosis, the main priority should be the cancer diagnosis and survival, Vij emphasizes.

“The discussion about infertility is hard to have, but it (needs) to be (talked about) upfront,” she says. “We recommend that all men with testicular cancer do sperm banking. Ideally, this is done prior to removal of the testicle.”

Sperm banking is the process of collecting semen and examining it under a microscope to count sperm cells to determine how healthy they are. The sperm cells are then frozen and stored. This process is sometimes called sperm cryopreservation.

Jay Erickson chose sperm banking after his testicular cancer diagnosis in 2013.

A small population of men may not be able to provide ejaculate or do not have sperm present in the ejaculate. In these men, surgeons can try to remove sperm from the testicle during the orchiotomy (a surgical procedure to remove one or both testicles), Vij says. This process is called testicular sperm extraction.

Jay Erickson, 46, chose to bank sperm after receiving a testicular cancer diagnosis in 2013. He says the disease was pretty advanced at diagnosis, with the initial ultrasound showing a large mass in his abdomen with tumors throughout his lymph node system and lungs. The physicians initially thought Erickson had sarcoma, but bloodwork eventually showed elevated levels of the hormone HCG.

Erickson’s physicians told him he had pure testicular choriocarcinoma, another rare form of testicular cancer occurring in about 0.19% of all testicular tumors.

Through fertility preservation before cancer treatment, Jay Erickson's daughter Juniper was born a few months after his last surgery, which he says was a big part of his healing.

Choriocarcinomas tend to be aggressive, and Erickson was told that this type of cancer was not always responsive to chemotherapy.

Prior to his diagnosis, he and his wife had been trying to get pregnant.

“During that initial conversation, we discussed prognosis, medical details and a treatment plan, but when infertility came up, it was really not on my radar,” Erickson says. Recalling the details of that day still elicits emotions for him. “I was going to start chemotherapy in two or three days, and the people at (Memorial) Sloan Kettering (Cancer Center) had a fertility specialist right there at the appointment with a messenger standing by — ready to bring a (sperm) specimen to a Manhattan cryopreservation bank that day.”

The details are hazy, Erickson says, but the specialists told him that there would be a good chance to have children using banked sperm and in vitro fertilization (IVF). To improve the couple’s chances of success, the specialists said, he should bank as many specimens as he could in the days leading up to start of his treatment.

Over the next year or so, Erickson endured the orchiotomy, several rounds of chemotherapy, a retroperitoneal lymph node dissection and several surgeries to remove masses from his lungs and a small bowel obstruction. During his treatment, he and his wife made the decision to initiate IVF.

“I had been able to bank three specimens. We were told one was not good quality, and we had one failed round of IVF,” Erickson says. “It was the last vial, our last hope.”

Their daughter Juniper, 6, was born only a few months after Erickson completed his last surgery. His daughter’s birth, he says, was a big part of his healing.

Jay Erickson, and his wife, Katie Rose, have another child, Iris, who was conceived naturally at a time when the couple thought they should consult adoption lawyers.

Men treated for testicular cancer may still be able to have children naturally after their diagnosis. Vij says men who are treated with only surgery may not need to wait at all to attempt to have children. Treatment with chemotherapy and radiation, however, warrants waiting.

In general, Lipshultz recommends that men wait at least two years to try to have children naturally.

“Sperm production takes three to four months, so if you want to have sperm that have not experienced the impact of the chemotherapy or the testicular cancer itself, men need to wait at least a year or four cycles of sperm production,” Lipshultz says.

If men want to try to have a childly naturally, Campbell recommends trying for at least a year before consulting a fertility specialist.

“There is always a major component of psychosocial change that occurs post-treatment for testicular cancer that can contribute to stress, body image concerns or other things that could potentially impact fertility as well,” Campbell says.

Midkiff says that after he completed his treatment, he and his first wife tried to get pregnant for a period of time.

“I knew, though, that something was different (afterward) based on the volume of semen,” Midkiff says.

Tests confirmed azoospermia, which means there is no sperm in a man’s semen. Midkiff admits that he briefly thought about not being able to pass along biological traits to his child and about his wife not having the opportunity to be pregnant and carry a baby.

“I worked in education, though, and kids are a pretty big part of my life,” Midkiff says. “The idea of fostering or adopting kids was something I had already wanted to do anyway, so we ended up going that route.”

Today, he has two kids, ages 18 and 16, with his first wife and three more children, ages 11, 10 and 6, with his second wife.

After using their last specimen to conceive their daughter Juniper, Erickson and his wife also considered adoption. Erickson had undergone sperm analysis after his treatment and received a diagnosis of teratospermia, a condition characterized by abnormally shaped sperm.

“We were researching and meeting with adoption attorneys when my wife got pregnant,” Erickson says. That pregnancy was their daughter Iris, now 4 years old.

Campbell says that every man diagnosed with testicular cancer should be counseled on sperm banking at the initial diagnosis and that these conversations should be part of standard of care.

“I see patients who are coming in with a diagnosis of testicular cancer, and I refer them for sperm banking,” Campbell says. “I go through the reasons why sperm banking should be considered, even if patients are not interested in conceiving in the near future.”

Campbell says that conversations about fertility should also occur with men who say they’re done having children.

“We discuss the fact that with testicular cancer treatment, there is no guarantee that they will be infertile,” Campbell says. “They have to still be careful of having children unintentionally.”

For those men who choose to bank sperm, Lipshultz says there are issues related to cost and access. A lot of the cryopreservation banks are in major urban areas, but some banks do offer mail-in sample kits.

The average cost of initial sperm banking and analysis is about $1,000, with a yearly fee of approximately $300 for storage, according to the Alliance for Fertility Preservation. These fees can vary based on location. The cost of testicular sperm extraction can be much higher, between $6,000 and $16,000. One must also consider the cost of using the sperm for artificial insemination, which costs about $1,000 per cycle, or IVF, which can be $15,000 or more.

Midkiff was diagnosed with testicular cancer in October 2001 and finished his treatment in March 2002. He has had no cancer scares since then. Although he did not undergo any type of fertility preservation, he says he has no regrets.

“The No. 1 thing I would tell someone is don’t wait,” Midkiff says. “My cancer was so aggressive that if I had waited, I wouldn’t have made it.”

Erickson is more than six years out from his last treatment and still undergoes annual follow-up screening. He is very grateful he was able to bank sperm and encourages others to do the same.

“Bank as much as possible so that you have options,” Erickson says. “You don’t have to make a decision that day. Bank it and then forget about it, and focus on yourself, healing and getting better. That is No. 1.”

Erickson likened sperm banking or other methods of fertility preservation to the proverb “Trust in God, but tie your camel.” Have faith but take action.

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Despite a testicular cancer diagnosis, men have options when it comes to starting or growing their family.

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When Jo Anne Schatz, 69, talks about the latest treatment she received for her endometrial cancer, she describes it as an “eraser.”

“It was amazing,” Schatz says. “It just wiped my cancer out.”

The drug, Keytruda (pembrolizumab), is a type of cancer treatment called immunotherapy, designed to harness a person’s immune system to identify and destroy the cancer. It is just one of the targeted treatments approved by the Food and Drug Administration (FDA) for or being developed for the treatment of endometrial cancer.

Unlike traditional chemotherapy, which acts against cancer cells and healthy cells alike, targeted treatments are aimed at specific aspects of the cancer cells.

Keytruda hitting its target is what Schatz credits with saving her life.

Schatz, a former addiction specialist from Philadelphia, received a diagnosis of endometrial cancer in May 2015 after experiencing unexpected vaginal bleeding. She had never heard of the disease.

“My primary care doctor told me to contact my gynecologist; within two weeks, I was seeing a specialist at Fox Chase Cancer Center and headed in for a complete hysterectomy,” Schatz says.

Endometrial cancer is a disease in which cancer cells form inside the lining of the endometrium, or uterus. Vaginal bleeding and pelvic pain are common symptoms.

“Endometrial cancer is the most common of all gynecological cancers in the United States,” says Dr. Christina S. Chu, professor in the Department of Surgical Oncology at Fox Chase Cancer Center in Philadelphia. “Fortunately, the vast majority of endometrial cancers can be treated surgically with the removal of the uterus, ovaries, fallopian tubes and cervix. Most are cured with this surgery plus or minus radiation.”

Some patients — 13% — who receive a diagnosis of endometrial cancer, however, will have their disease recur. After surgery, Schatz underwent several rounds of radiation and chemotherapy to destroy any remaining cancer cells. After a brief remission, her cancer recurred, metastasizing to the peritoneal lining, and her physicians began to look for more targeted treatment options.

“When we started to get down to the genomic levels of these tumors, we realized that just because some endometrial cancers may look (similar) under the microscope, they may still behave biologically different based on genomic signature,” says Dr. Emily M. Ko, assistant professor of obstetrics and gynecology at Pennsylvania Hospital of Penn Medicine in Philadelphia. “Based on that genomic signature, there may be biologic pathways that we can target.”

That is what happened to Schatz, who was told that her type of endometrial cancer had a genetic component called MSI-high.

MSI stands for “microsatellite instability.” When disease is MSI-high, the cancer cells have a high number of mutations within microsatellites, which are short, repeated sequences of the DNA. These signify abnormalities in DNA repair, which can be targeted with certain drugs.

In 2017, the FDA approved Keytruda for use as a treatment for any solid tumor that was MSI-high, had progressed after prior treatment and had no satisfactory alternative treatment options.

“This was important for patients with endometrial cancer because (approximately) 30% of patients with endometrial cancer will have tumors that are MSI-high,” explains Dr. Shannon N. Westin, associate professor in the Department of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center in Houston.

One study evaluating the use of Keytruda in patients with MSI-high tumors showed that among a small group of women with endometrial cancers, more than half saw their tumor respond to the treatment, and the majority had at least some clinical benefit.

“A larger proportion of patients with endometrial cancer will have microsatellite-stable disease,” Westin says. “For those patients, there is a newer FDA-approved targeted therapy combining Keytruda with Lenvima (lenvatinib).”

Indeed, in late 2019, the FDA approved the immuno- therapy Keytruda with Lenvima for patients with endo- metrial cancer that is not MSI-high and whose disease has come back after prior chemotherapy. Lenvima is a multiple-receptor tyrosine kinase inhibitor. The drug works by blocking the action of abnormally activated proteins that signals cancer cells to multiply. A study of this combination showed that approximately one-third of endometrial tumors responded.

Finally, some patients with endometrial cancer may qualify for treatment with a drug targeting NTRK gene fusions, which are estimated to occur in only a small percentage of endometrial cancers. Rozlytrek (entrectinib) and Vitrakvi (larotrectinib) are approved for adults who have solid tumors with this specific genetic alteration.

“Not every endometrial cancer that comes back or spreads will have one of the characteristics to qualify for the currently available targeted treatments. These women may want to ask their physicians about potential alternatives,” Ko says.

Kim Bryant, 61, a former special education teacher from Texas, did just that when she was told in May 2019 that her endometrial cancer had spread. After receiving her diagnosis in March 2016, Bryant initially underwent surgery and radiation for the cancer. After its first recurrence a year later, she had additional surgery followed by radiation and chemotherapy.

“At that point, my local oncologist said he had done all he could and referred me to MD Anderson,” Bryant says. “I was given a choice between two trials. I was enrolled in one for about a year and my cancer progressed. I have had more success with the second trial.”

The second clinical trial is testing a three-drug combination of the hormone therapy Femara (letrozole); Afinitor (everolimus), a drug designed to target a protein called mTOR that promotes cell growth; and Kisqali (ribociclib), a CDK 4/6 inhibitor that is designed to interrupt the cell cycle that drives growth of cancer cells.

“CDK 4/6 inhibitors have been studied in breast cancer and are thought to potentially be synergistic when used with other hormonal drugs,” Ko says.

For her first clinical trial, Bryant had been making a four- hour drive once a week from Dallas to Houston to receive treatment. On the current trial, all three drugs are oral and can be taken at home.

“All three oral treatments (are) so much easier because there are no infusions,” Bryant says. “I only have to go down once every three months for bloodwork and other testing.”

Bryant remains on treatment and says that, so far, the cancer is responding well.

In addition to mTOR and CDK 4/6 inhibitors, clinical trials are also testing a class of drugs that inhibit poly (ADP-ribose) polymerase — more commonly known as PARP inhibitors. This class of drugs is approved for certain breast and ovarian cancers that have an inherited mutation in the BRCA gene

or have a certain genomic instability called homologous recombination deficiency (HRD), a type of DNA repair defect.

“There are a number of trials exploring these drugs alone or in combination with other targeted agents to see if there is activity in endometrial cancer,” Westin says. “Probably about 20% of endometrial cancers have mutations in BRCA or other abnormalities in HRD pathway members, but there may be other abnormalities in endometrial cancer that predict benefit, so none of the trials (is) being selective.”

There are also trials exploring other immunotherapy drugs that target a protein called PD-1 or PD-L1, immunotherapy drugs in combination with chemotherapy or other targeted agents, and agents targeted against other disease pathways such as the PI3K or MEK pathways, Westin says.

Right now, these targeted therapies are considered second- line treatments — given after a first disease recurrence — because they are not as effective as primary chemotherapy for most patients, according to Chu.

“Trials are ongoing to test targeted therapies in combination with chemotherapy in the first-line setting, though,” Chu says.

There have not been any completed clinical trials yet comparing the standard chemotherapy with these new targeted treatments, but they are in progress, according to Ko.

“What we are learning is that perhaps side effect profiles may be better in targeted treatment, meaning it may be worthwhile to consider an alternative targeted therapy up front in treatment rather than saving it for down the road,” explains Ko.

For example, immunotherapy drugs such Keytruda do not have the traditional side effects seen with chemotherapy, such as hair loss, nausea or vomiting. Because the drug works by attempting to stimulate the immune system, many of the side effects seen with Keytruda are related to the immune system, Chu says. Similarly, side effects seen with Lenvima, which works by affecting blood vessels, can be related to a patient’s blood vessels, such as high blood pressure.

Schatz says that during her treatment with Keytruda, she experienced muscle aches, pains and fatigue. Other common side effects associated with Keytruda include headache, fever, skin rash, constipation, loss of appetite and diarrhea.

“On chemotherapy, I was often sick for a full week, then a little better before preparing to go back for another treatment,” Schatz says. “On the trial, I was able to cook and care for myself and establish a routine.”

Bryant says that side effects during her most recent clinical trial also have been tolerable.

“I have had some decrease in appetite and some fatigue, but not enough that it keeps me from doing what I want to do,” Bryant says. “It has only slowed me down some.”

Many of the side effects related to targeted therapies can be managed easily if caught early, Westin says.

“This takes good communications between a patient and their health care team — and preparation — so that a patient knows what to look for,” Westin says.

In addition to a patient’s tumor having the right “target,” the health care team will consider these possible side effects in their decision on whether a patient might qualify for treatment with a targeted therapy.

“We look at the best data we have available, the tumor characteristics and the overall health of each patient to decide if a targeted therapy is best,” Ko says.

Schatz credits much of her progress not only to targeted therapy but also to advocating for herself and her treatment. She had one doctor who encouraged her to continue treatment, whereas another told her to stop. Since stopping treatment with Keytruda, Schatz has follow-up scans every four months, as well as other regular monitoring. “I am also healthier,” she says. “I am on a ‘cancer-fighting’ plant-based diet. I take it one day at a time, but I am grateful to be alive and can feel my creativity coming back.”

Bryant, too, has been able to maintain an upbeat, “glass-half-full” attitude throughout her cancer journey, she says.

“I have surrounded myself with my faith, family and friends,” she says.

Westin applauds patients such as Schatz and Bryant for raising their voices and sharing their stories about endometrial cancer.

“Other tumor types get more attention, but endometrial cancer is one of the only cancer types where the incidence is growing,” Westin says. “A lot of women with endometrial cancer will be cured, but we have to be aware of their sisters in diagnosis who do not do as well and together raise our voices to shine more light on this problem. Hopefully that will allow us to get more funding and more companies interested in exploring new agents to treat endometrial cancer.”

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As more is learned about the biology of endometrial cancer, new treatment possibilities emerge.

Targeted Therapies Take Aim at Endometrial Cancer

Alisa Brenes, 63, is a 20-year survivor of lung cancer, and she spends a lot of time worrying about COVID-19. “I first became aware of COVID-19 through my lung cancer community, which was discussing this new disease and how it affects the lungs,” Brenes recalls. “At first, I didn’t feel any panic, (as) most of the local cases were in Westchester, (New York), but shortly after that my office told us we were going home and New York City was going on pause.”

Brenes, a legal assistant living in Manhattan, is just one of the many hundreds of thousands of people in the United States who have survived lung cancer or are facing a new diagnosis and are trying to understand their risks in what has become the COVID-19 era.

What's The Risk of Cancer Care During COVID-19? 

According to the Centers for Disease Control and Prevention (CDC), COVID-19 is a respiratory illness caused by a virus that can spread from person to person, and its symptoms can range from mild or none to severe illness. The virus cells first infect the respiratory and nasal lining, causing inflammation, explains Dr. David M. Jablons, chief of general thoracic surgery at the University of California, San Francisco and a professor of thoracic oncology at its Helen Diller Family Comprehensive Cancer Center.

“That is why some patients can get a cough or shortness of breath, and in severe cases, people can develop pneumonia or interstitial lung disease,” a group of disorders that can cause progressive lung scarring, Jablons says.

Everyone is at risk for getting COVID-19, but certain groups, including older adults and those of any age with serious underlying medical conditions, might be at a higher risk for severe illness if they contract the virus, according to the CDC.

Lung cancer itself likely does not put people at increased risk of contracting COVID-19, but some of the other illnesses or treatments associated with the malignancy may increase the severity of the virus, according to Dr. Joshua K. Sabari, a medical oncologist at NYU Langone Health’s Perlmutter Cancer Center and an assistant professor at its NYU Grossman School of Medicine in New York City. One of those conditions is simply age, as the average patient who receives a diagnosis of lung cancer is 70 years old.

“Other pulmonary comorbidities (coexisting illnesses) associated with lung cancer, such as chronic obstructive pulmonary disease and the use of certain cytotoxic chemotherapies to treat lung cancer, may also increase risk compared with targeted therapies or immunotherapy and chemotherapy combined,” Sabari says.

Although chemotherapy leaves patients with lung cancer immunocompromised, meaning that their bodies are more prone to infection, study results have been mixed about whether the treatment contributes to the risk of contracting COVID-19 or having a severe case.

Some of the best data available on the relationship between lung cancer and COVID-19 are from the TERAVOLT global registry study. Recently published data from TERAVOLT showed that patients with stage 4 non-small cell lung cancer face a higher risk of complications and death if they get COVID-19. When various factors were looked at independently, the study showed that older age, treatment with chemotherapy and the presence of comorbidities were associated with an increased risk of death among these patients. However, in an analysis of multiple factors looked at together — typically considered a more accurate measure — only smoking history was associated with an increased risk of death.

Another study, this one conducted by researchers at Memorial Sloan Kettering Cancer Center in New York City, analyzed the cases of 102 patients who had both lung cancer and confirmed COVID-19; they found that the virus was severe in 62% of the patients but accounted for only 11% of the deaths among the group studied. Chronic obstructive pulmonary disease and smoking status were associated with increased severity of COVID- 19, but recent chemotherapy was not.

Most patients with early-stage lung cancer found incidentally through screening or on a chest X-ray prior to another surgery are likely not at any increased risk from COVID-19 compared with the general population, Jablons says, adding that he is not aware of any patients with lung cancer at his cancer center who contracted COVID-19 since the pandemic started.

Although her evaluation is anecdotal rather than scientific, Brenes has seen a similar trend: None of her close friends from the lung cancer community have told her they had the virus, and Brenes has heard through the grapevine of only a handful of people within that community who have been sick with the illness.

One important thing to remember is that cancer will not “shelter in place” when people do, Jablons says.

“In the past few months, there have not been as many incidental early-stage cancers found through screening because people are avoiding going to the hospital or for routine health care,” he says. “That may be a bigger risk to someone’s long-term survival than COVID-19.”

Brenes admits that she delayed some of her regularly scheduled follow-up appointments.

“I was a few months late for my routine low-dose CT (scan),” she says, referring to a screening test for individuals with a history of smoking that checks the lungs for lesions. “I was afraid to go to my cancer center — Mount Sinai in New York — which was a COVID-19 hospital. I was afraid to take mass transportation or to take a cab.”

To lower her risk for exposure, Brenes eventually called to have her scans scheduled at a private radiology center within walking distance and asked to have the first appointment of the week after the CT scanner had been out of use for 48 hours over the weekend.

Sabari, who practices in New York City, says he knows of a lot of patients who are fearful of in-person health care visits.

“We definitely missed opportunities to diagnose patients early and cure their disease,” Sabari says. “We have also seen a lot of mortality in lung cancer patients from not accessing care or getting the correct care during the pandemic.”

Right now, in any area with lower COVID-19 rates, patients should not delay treatment, he says. Even during the peak of the pandemic, he continued to treat patients with stage 2 or 3 disease, for whom the goal of chemotherapy is to cure the cancer.

Even in those areas with higher rates of COVID-19, patients should actively communicate with their health care teams on the best way to approach treatment, according to Dr. Konstantinos Leventakos, a medical oncologist and an assistant professor of medicine and oncology at Mayo Clinic in Rochester, Minnesota.

For some patients with advanced disease, the recommended treatment approach may include enrolling in a clinical trial. Fortunately, most centers have these studies up and running again. “Some trials halted enrollment at the start of the pandemic, but we are now able to reopen them safely,” Leventakos says.

The requirements of each clinical trial are different, and some may mandate that patients undergo COVID-19 testing before they receive treatment. Other changes made to the design of some trials during the pandemic aim to make participation more accessible, for instance, by requiring fewer cancer center visits than would otherwise be expected or using televisits or local providers when possible. “We have to constantly balance the risk of potentially life-threatening infection in patients with lung cancer with the short- and long-term consequences of delaying cancer care,” Leventakos says. “That is why good communication with your oncology team is the only way to make the best decision.”

According to Jablons, if required to come onsite, patients are safe at most treatment centers, especially at high-volume centers of excellence where thorough precautions have been put into place to prevent transmission of the virus. If concerns exist, patients should inquire about the safety precautions that are being taken for both employees and patients at the facility.

Tiffany Fagnani, 39, said she has experienced some cancellations or rescheduling of treatment and follow-up appointments at Fox Chase Cancer Center in Philadelphia since the pandemic began, but that she feels safe going in when necessary because the center has been able to maintain a COVID-19-free status.

Fagnani, a nurse case manager living in Pennsylvania, received a diagnosis of stage 4 lung cancer with brain metastases in July 2017. Today, even though the disease is stable, she understands the importance of not delaying care.

“I know that I still have to go in for certain appointments, and for others I am able to talk with my team using telehealth,” Fagnani says. She sees this compromise as the best way to prioritize her care while still being cautious.

When Fagnani goes out, she wears a mask and checks to make sure everyone around her is doing the same. If they are not, she avoids going near them. She also avoids crowded spaces where social distancing is not possible.

One challenge for Fagnani was that she was in the process of having a new home built when the pandemic hit.

“When we did walkthroughs, I asked that it only be me, my realtor and the builder,” she says. “We were all masked, and we were all socially distanced.”

In the more crowded setting of New York City, Brenes also takes precautions. “I always wear a mask if I have to leave my apartment or even for the laundry room, to get mail from the lobby or to get a home delivery,” Brenes says.

“I wear a disposable mask with a reusable lung cancer awareness mask over it.”

As many public service announcements have emphasized throughout the pandemic, frequent hand washing and keeping fingers away from the face are also important. Another way to protect health is to keep the lungs and body as healthy as possible, Leventakos says.

“At home, a healthy lifestyle can help overall health: Make healthy choices in order to keep your body strong,” Leventakos recommends. “Get enough sleep so that you wake feeling rested. Choose a healthy, balanced diet. Aim to get exercise most days of the week.”

Importantly, he says, find healthy ways to reduce stress.

“I do have high anxiety, and it has affected my mental health,” Brenes notes. To help manage her anxiety, Brenes has signed up for meditation and chanting classes on Zoom, which help her relax. When she feels anxious, she tries to focus on her breathing. Brenes also turns to the lung cancer community and its Zoom chats to talk about her fears and concerns.

Patients in need of support can turn to online communities like LUNGevity, which offers weekly virtual meetups for patients, survivors and caregivers across the country. Similarly, the GO2 Foundation for Lung Cancer has moved its Lung Cancer Living Room, a monthly patient education and support series, to a virtual plat- form. Fagnani says that she still sees some friends in person, at least the ones she knows are following all appropriate COVID-19-related precautions. She has also found a renewed joy in cooking.

“I have been doing grocery delivery, and sometimes there are certain things that you
can’t get,” Fagnani says. “I have learned to open the cupboard and see what I have to create a new meal or new recipes. I have really enjoyed that.”

As winter months approach, Sabari says that patients with lung cancer should be cautious but not fearful.

“I recommend that all patients get a flu shot, and if you are 65 or older, get the high-dose flu shot,” Sabari says. “We can’t become complacent. We have to continue to wear masks, wash hands routinely (and) socially isolate and distance when possible.”

He also emphasizes that, with all that health care experts have learned about COVID-19 since earlier this year, the benefits of treating lung cancer far outweigh the risks of the virus.

“Take every possible precaution that you can, but until we have a vaccine or until a greater proportion of the population has antibodies, COVID-19 is something that is going to remain with us, and dealing with it has to become a new normal,” Sabari says.

Leventakos agrees. He recommends that all patients and their families or caregivers get familiar with the COVID-19 precautions at their clinic or hospital and closely monitor the levels of the virus in their local area.

Finally, he says, it is important to remember that each patient’s experience is unique.

“Even though, statistically, COVID-19 might cause more complications in patients with cancer, and lung cancer, specifically, every patient has a different course,” Leventakos says. “This is why it is important for patients to communicate any change in their health with their oncology team.”

Patients with lung cancer should take all recommended precautions against COVID-19, but they must also keep up with their cancer care, doctors advise.

Patients With Lung Cancer Should Be Cautious, But Not Fearful of COVID-19

Darryl Elzy, 60, an Air Force retiree from North Carolina, has been living with prostate cancer for about 12 years and has been a participant in clinical trials almost as long.

“Every time they offered me a trial, I said, ‘Sign me up!’” Elzy says.

Earlier this year, Elzy completed a clinical trial — his third — testing PARP inhibitors, a class of drugs that is new to the treatment of prostate cancer. PARP is an enzyme in cells that helps repair DNA when it becomes damaged. The inhibitors can block PARP in cancer cells, keeping them from repairing their damaged DNA and causing them to die.

PARP inhibitors were first approved by the United States Food and Drug Administration (FDA) in 2014 to treat certain ovarian cancers and, more recently, to treat breast cancers. In May, two PARP inhibitors became the first in their class approved as therapies for certain metastatic prostate cancers, ushering in a new era of treatment with targeted drugs. 

While drugs that suppress the hormones that fuel metastatic prostate cancer are the mainstay of treatment, PARP inhibitors can help certain patients whose disease has become resistant to those medications.

In particular, the patients most likely to benefit from PARP inhibitors are those who have tumors with DNA repair defects. It is for those patients that Lynparza (olaparib) and Rubraca (rucaparib) are intended.

“Our bodies have mechanisms in place to repair damage that happens to our DNA,” explains Dr. Veda N. Giri, director of cancer risk assessment and clinical cancer genetics at the Sidney Kimmel Cancer Center at Thomas Jefferson University in Philadelphia. DNA damage happens on a daily basis and can be caused by things such as exposure to ultraviolet light, radiation, cell turnover or substances in the environment.

“DNA houses genes that act as the control center for our cells and tell the cells what to do,” Giri says. “If DNA is damaged in the region that houses those genes — called DNA repair deficiency — it can lead to improper signals and result in disease conditions such as cancer.”

Mutations in DNA repair genes can be acquired, meaning that the mutation develops in the tumor as it grows, or they can be inherited, meaning that the glitches are present throughout the body in all of a patient’s cells.

“Reports state that about 25% to 30% of men with metastatic prostate cancer have acquired, tumor-only DNA repair deficiency mutations, and about 12% to 17% of men have inherited mutations,” Giri says. “For men with earlier-stage prostate cancer, about 5% to 7% have inherited mutations.”

Among the most common DNA repair deficiency mutations are BRCA1 and BRCA2 gene mutations and a mutation in ATM, a “BRCA-like” gene also involved in DNA repair, Giri says.

DNA repair deficiencies affect signaling pathways, strings of chemical reactions that pass messages to a cell from its environment about how to behave. Pathways are associated with proteins encoded by specific genes.

When cancer cells have a DNA repair deficiency in the BRCA pathway, for example, the cells adapt and use an alternative pathway to repair themselves. PARP is one of those pathways. Using PARP inhibitors in patients who have an existing DNA repair deficiency delivers a one-two punch (known in scientific terms as “synthetic lethality”) to the cancer cells, which leads to cell death.

The exact percentage of men with DNA repair mutations who will benefit from these drugs is still being established, according to Dr. Joshua M. Lang, associate professor of hematology, medical oncology and palliative care at the University of Wisconsin School of Medicine and Public Health in Madison. That is because, for many years, it was thought that genetics were not as important in prostate cancer as in other cancers.

“Fundamentally, this is all a new area in prostate cancer,” Lang says. “In the last five years, we have become aware of genetic changes associated with prostate cancer not just in the tumor cells, but also in genes that can be inherited.”

Previously, the majority of genomic testing was done in samples taken during prostatectomy, meaning the surgical removal of the prostate, Lang explains. While inherited mutations can be found through tests of blood, saliva or tissue samples, experts are learning that acquired mutations — the ones that occur in the cancer as it grows — are not always present in the prostatectomy sample and may only appear later in biopsies taken from metastatic sites.

Elzy received a diagnosis of prostate cancer when he was 48. Although the average age at diagnosis is about 66, men found to have an inherited BRCA2 mutation are more than four times as likely than those without the mutation to receive a diagnosis before that age. Compared with men who don’t have the mutation, the risk of prostate cancer is more than eightfold higher for men who have the BRCA2 mutation and are 65 or older.

Elzy was initially treated with radiation and a prostatectomy to remove the tumor.

“My doctor realized that a portion of my cancer was outside of the margin of being able to remove it, so I knew that there was still the possibility of lingering tumor that we couldn’t reach,” Elzy says.

To address the lingering cancer cells, Elzy underwent chemotherapy, but his blood level of the protein prostate-specific antigen (PSA) — which often rises in response to the growth of prostate cancer — continued to increase. That is when his physician began to look for clinical trials.

“My first two trials both had good results to start, but all of a sudden the PSA would start rising again,” Elzy says.

Eventually, his doctor decided that Elzy should be sent for genetic testing. The National Comprehensive Cancer Center now recommends that all men with metastatic prostate cancer undergo blood tests to determine if they have inherited DNA repair deficiency. Testing can also be done on tumor samples to look for acquired mutations.

Elzy’s results revealed a BRCA2 mutation that his doctors suspect he inherited from his mother, who died of breast cancer in 1992. If genetic testing had been more advanced back then, Elzy, who has no siblings or children, likely would have been advised to undergo genetic testing to find out if he had inherited the mutation.

Dr. Maha Hussain, deputy director of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University’s Feinberg School of Medicine in Chicago, noted that, at the moment, having information about inherited mutations does not change the initial approach to treating newly diagnosed prostate cancer. Similarly, knowing a patient is BRCA-negative when newly diagnosed does not eliminate the possibility that the tumor will acquire a mutation as it grows.

“This could all change as our knowledge improves,” Hussain says. However, in her practice, Hussain says she has begun to send tissue for testing in men with high-risk, 

hormone-sensitive disease or prostate cancer that has recently stopped responding to hormone-suppressing drugs. “Getting prepared and ahead of the game is the best approach,” she says. “Clearly, testing for germline has implications for blood relatives, and I offer patients the opportunity.”

In Elzy’s case, once he learned that he had an inherited mutation, he was quickly recruited into a clinical trial of a PARP inhibitor.

Lynparza and Rubraca are the only PARP inhibitors approved by the FDA so far for men with metastatic castration-resistant prostate cancer (mCRPC), meaning disease that has spread beyond the prostate and has progressed on hormone-suppressing treatments. Lynparza is approved to treat men with cancer that progressed after treatment with one of two hormone-based prostate cancer therapies, Xtandi (enzalutamide) or Zytiga (abiraterone). 

To be eligible, patients must have a mutation in one of the homologous recombination repair (HRR) genes, specifically BRCA1, BRCA2 or ATM, which constitutes a DNA repair deficiency. Patients can be selected as good candidates to receive the therapy based on the results of an FDA-approved companion diagnostic for Lynparza.

Rubraca is approved for men with mCRPC and a BRCA1 or BRCA2 mutation who have received treatment with androgen receptor-directed therapy and a taxane-based chemotherapy.

Lynparza was approved based on the results of a clinical trial comparing the drug against Xtandi or Zytiga. Men with BRCA1, BRCA2 or ATM mutations were assigned to treatment with Lynparza, while men with any of 12 other mutations associated with HRR were given Xtandi or Zytiga. Men treated with the PARP inhibitor went twice as long before experiencing disease progression (7.4 months versus 3.6 months), and early data showed that their overall survival was nearly five months longer than those in the group that received hormonal treatment (19.1 months versus 14.7 months). 

In patients who had tumors that could be measured, about one-third of those who received Lynparza saw their tumor respond to the drug compared with only 2% of men treated with the other drugs. When looking at all the men in the study, including those with mutations other than BRCA or ATM, a meaningful delay in disease progression was observed among those who took Lynparza compared with investigator’s choice of treatment (5.8 months versus
3.5 months).

Response to Lynparza also may vary depending on the type of mutation, with the phase 2 TOPARP-B study showing that 80% of patients with a BRCA1 or BRCA2 mutation responded to the treatment while 37% of patients with ATM mutations responded.

Rubraca was approved based on the results of a trial in which all patients received the PARP inhibitor and a hormone-suppressing drug. In this study, 42% of the men who participated saw their tumor respond to the drug. “There are many ways to assess response, including the rate of PSA decline, the shrinkage of tumors and delaying cancer progression,” Hussain said. 

“Based on the PROfound trial, the odds of response to Lynparza as measured by PSA decline of 50% or greater was seen in 43% who had BRCA1, 2 or ATM mutations compared with 8% (six of 77) in the patients who received Zytiga/prednisone or Xtandi. In the overall study population, a PSA response was confirmed in 30% in the Lynparza group compared with 10% in the control group. The data also show benefit in terms of significantly delaying pain progression, which is a critical point from a quality-of-life perspective.”

Patrick McGuire, 73, a retired scientist from Wisconsin, has benefited from PARP inhibitors. McGuire received a diagnosis of prostate cancer in October 2015. After under-going prostatectomy, he learned he had metastatic disease and began to participate in clinical trials. Like Elzy, he found that each trial led to only a temporary improvement in his disease.

Primed to knock out cells vulnerable due to DNA-repair problems, PARP inhibitors are ushering in a targeted-drug era in prostate cancer treatment.

Leah Lawrence

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