Don Vaughan

The biopsy had clear margins and (my team) would be following me for the rest of my life. Today I’m cancer free.

Anna Bass, 62, of Victoria, Virginia, had been a longtime smoker, so she was not surprised in October 2016 when she was diagnosed with adenocarcinoma in her right lung. Her doctor had noticed a small spot on a CT scan two years earlier after she quit smoking. She had opted to hold off treatment, hoping that the lesion would not grow larger.

Bass, a secretary at Victoria Baptist Church, underwent a lobectomy to remove the top right lobe of her lung. She was happy to learn that she required no further treatment. 

“My brother-in-law is an oncologist, and he said if they didn’t tell me to get chemotherapy or radiation therapy, it was because they weren’t necessary,” Bass recalls.

Throughout her cancer journey, Bass received an array of supportive care from her medical team, friends and family. Nurses addressed her pain, helped her learn to breathe properly again and demonstrated how to use an oxygen concentrator. She was encouraged to exercise, so she started walking.

But the most significant support Bass says she received from her care team was reassurance that her cancer had a good chance of being eliminated and likely would not reoccur. 

“They told me that the cancer had been slow growing, the biopsy had clear margins and they would be following me for the rest of my life,” Bass says. “Today I’m cancer free.”

Bass’s story illustrates the many benefits of supportive care for patients with lung cancer, a population that tends to skew older and have more comorbid conditions than those with other forms of cancer. Bass, for example, has chronic obstructive pulmonary disease and is a recovering alcoholic, which restricts her use of opioids to alleviate pain. 

When started early in the treatment continuum, guidelines show, supportive care can help patients live longer, improve their quality of life and cope better with the side effects of their disease and treatment, as well as comorbid conditions.

The terms supportive care and palliative care are sometimes used interchangeably, but there can be differences. The Multinational Association of Supportive Care in Cancer defines supportive care as “the prevention and management of the adverse effects of cancer and its treatment. This includes management of physical and psychological symptoms and side effects across the continuum of the cancer experience from diagnosis through treatment to posttreatment care.”

Palliative care, according to the Center to Advance Palliative Care, is “specialized medical care for people living with serious illnesses. It is focused on providing patients with relief from the symptoms and stress of a serious illness — whatever the diagnosis. The goal is to improve quality of life for both the patient and the family.”

Lung cancer is a prevalent disease with a high incidence rate, so it has received a lot of attention from researchers over the years. This has led to advances in treatment and supportive care. 

“This patient population still has a lot of needs, but the good news is that their prognosis and their experience have gotten better,” says

Dr. Jennifer Temel, co-director of Massachusetts General Hospital’s Cancer Outcomes Research and Education Program and professor of medicine at Harvard Medical School in Boston. 

“Targeted therapies and immunotherapy have (become) more effective, so patients are living longer. And for the most part, the physical symptoms associated with these treatments are less. This doesn’t obviate the need for supportive and palliative care for lung cancer patients, but I think their needs have changed over time and they are becoming more like other advanced cancer populations.”

Supportive and palliative care for patients with lung cancer commonly involve the entire care team, observes Betty Ferrell, director of nursing research and education and a professor at City of Hope in Duarte, California. A care team includes physicians, nurses, social workers, physical therapists, occupational therapists, nutritionists, chaplains, psychologists and psychiatrists. Other aspects may include such novel approaches as music therapy, art therapy, acupuncture and massage.

“There are four key disciplines in (patient) care: medicine, nursing, social work and chaplaincy,” Ferrell says. “Physicians evaluate the patient’s medical condition, while nurses do a lot of symptom management and handle other responsibilities. The social worker assists the patient and family with issues such as finances, transportation, and in-home services — you can’t provide good palliative care without a social worker. And chaplaincy addresses the patient’s spiritual needs. Chaplaincy is critical.”

Dr. Arif Kamal, chief patient officer with the American Cancer Society and an associate professor of medicine and population health sciences at Duke University School of Medicine in Durham, North Carolina, agrees that spiritual support is vital. 

“Chaplaincy can help when patients have existential questions, such as ‘Why did the cancer happen to me? I’ve always been a good person,’” he says. “That question usually does not have a scientific answer, but a chaplain can be very helpful in helping the patient work through it.”

On the medical side, supportive and palliative care can address symptoms unique to patients with lung cancer, Kamal adds. These include shortness of breath, cough, difficulty swallowing, loss of voice, coughing up blood, confusion and issues around brain metastases.

Almost all accepted treatment guidelines recommend that supportive and palliative care be started at the time of diagnosis in order to address the symptoms and side effects of treatment before they become debilitating. However, this often is not the case, Ferrell says. 

“When people come to us with lung cancer, everyone is focused on treating the cancer — no one wants to talk about palliative care,” she explains. “Everyone’s response is, ‘It’s not time yet, let’s just start chemotherapy, then maybe later we’ll start palliative care.’ As a result, patients may not receive the supportive care they need until months after they should have. By the time they receive it, their quality of life has been severely impacted.”

Temel says, “We as a research and clinical community still have to find that sweet spot of figuring out how and when to integrate palliative care at the best time. But based on the data, early integration of palliative care for patients with challenging physical or psychological symptoms is still the best strategy.”

According to Temel, Massachusetts General Hospital was among the first institutions to demonstrate the benefits of initiating supportive and palliative care at the time of diagnosis. 

“More than a decade ago, we published a paper that showed that when you involve palliative care early in the course of illness for patients with incurable lung cancer, they have a better experience with their cancer and have better outcomes,” she notes. “They have better quality of life, fewer symptoms of depression, spend less time receiving chemotherapy and have better outcomes at the end of life.” 

Whereas a patient’s care team addresses the physical and emotional impacts of treatment, friends and family also play a critical role in supportive care. But there is always the risk of burnout. 

“If you’re caring for someone with lung cancer, you’re a 24-hour caregiver,” Ferrell says. “That can be a huge burden on some family members.”

Lisa, who asked that her last name not be used, is a writer and publisher in Raleigh, North Carolina. She was a caregiver for her older sister during her lung cancer journey starting in 2014. She assisted her sister with everything from housing and meals to transportation to and from treatment. 

Although she was happy to help, Lisa admits that the two years of caregiving were extremely stressful.

“There were times when my sister could be so critical that it was hurtful,” Lisa recalls. “Things were so hard at times that my goddaughter and I would go away so I could regain my composure. We would have a vent session and try to reboot my compassion meter.”

The family caregiving experience was far less dramatic for Christy Dawkins, 51, of Batesburg-Leesville, South Carolina. When she received a diagnosis of stage 3 non-small cell lung cancer in December 2019, her husband enthusiastically jumped into the role of caregiver. He took a monthlong sabbatical from work to care for her, doing all he could to keep her spirits up. 

Christy Dawkins learned how critical a support system is during cancer treatment and beyond. 

“He was there for me through all of the trips to receive radiation treatment and everything,” Dawkins says. “He really helped me through it.” Meanwhile, family friends created a meal train on Facebook so that the family wouldn’t have to worry about cooking during such a stressful time. 

We had people dropping off meals every night,” Dawkins recalls. “That was a huge help.”

Because lung cancer is more commonly diagnosed in older people, many family caregivers are older themselves and may be dealing with their own health issues, such as diabetes, heart failure and arthritis, Ferrell says. But their involvement can be extremely important to the patient. They are an additional pair of eyes and ears, and they often are directly involved in making sure the patient receives the care they need. 

But the heaviest burden they may bear is managing the patient’s emotional symptoms.

“We often don’t realize the role that caregivers play in helping patients
to keep going despite depression or anxiety,” Ferrell notes. “There’s a lot of fear, anxiety and emotions associated with living with lung cancer.”

Though supportive care for patients with lung cancer has been an integral part of treatment for many years, misconceptions still persist. 

“Most common is the belief that palliative care and hospice are synonymous, so that when we talk about palliative care, sometimes patients and their  families have worries that that means they’re at the end of life,” Temel explains. “It’s up to doctors, nurses and social workers to explain the distinction between palliative care and hospice care and the role of both services to allay those fears so patients are more accepting of the involvement of palliative care.”

“There must be educational campaigns that teach people how the emphasis during these conversations is not on end-of-life planning,” he says. “In my clinical practice, most patients are not dying. I have a large number of patients who have been seeing me for years because what we’re talking about is long-term distress, as opposed to an acute end-of-life type plan.”


Ideally, supportive and palliative care discussions are initiated by the patient’s medical team at the time of diagnosis. If that doesn’t happen, the patient and family caregivers should inquire about needed services, Ferrell says. “If my spouse or a parent is diagnosed with lung cancer, what do I want as a spouse or daughter? I want them to receive the best care possible,” she says. “So that’s the question every patient and caregiver should ask: ‘What about palliative care?’”

Concludes Temel: “I often remind my patients and their families, especially if I think they would benefit from something like palliative care but are resistant, that having cancer is hard for everyone and they should at least be open to accepting any support we can give them. Patients and their families talk about how it takes a village on their side to get through a cancer diagnosis. But it also takes a village on the clinician side. As an oncologist, I’m always going to do whatever I can to support my patients and their families. But the struggle is significant, so I rely on my colleagues who are social workers, nutritionists and psychologists to help out. Patients should take advantage of all of the services we have to help them navigate this very challenging time in their life.”

For more news on cancer updates, research and education, don’t forget to 

Articles

More awareness is needed to understand the benefits of both supportive care and palliative care in lung cancer.

Early Supportive Care Extends Life, Eases Cancer Symptoms

The speed at which cancer cells grow can be an important factor in determining cancer treatment. Among the best-known biomarkers for the rate of cancer growth is a protein known as Ki-67, which is expressed when tumor cells divide.

A high Ki-67 index indicates aggressive tumor growth. 

For example, Kate Laseter of Thornton, Colorado, was diagnosed with stage 2 invasive ductal carcinoma in September 2021 and informed that her Ki-67 score was 65%. Of note, the median Ki-67 score is 15%. 

Kate Laseter received a diagnosis of stage 2 invasive ductal carcinoma with a Ki-67 score of 65%.

As a histological technician with Theralink Technologies, Laseter immediately knew what that meant.

“It was very aggressive and growing rapidly and had invaded everything,” she recalls. “I looked at my (results) ... and I had less than 10% normal tissue in my biopsy.”

Because Laseter was just 29 when she noticed a lump in her breast, she was told that it was probably just a fibrous mass and to wait and see. She refused and demanded a biopsy. 

Based on her high Ki-67 score, she was placed on treatment immediately and received a chemotherapy regimen that included carboplatin and docetaxel in combination with the targeted therapies Herceptin (trastuzumab) and Perjeta (pertuzumab). She also underwent a bilateral mastectomy. 

In March 2022, she was declared in remission and cancer-free.

“My Ki-67 score clearly changed how quickly my care team wanted to start treatment on me,” Laseter observes. “If they hadn’t performed that test, my tumor could have just kept growing and possibly metastasized. It’s important for patients to educate and advocate for themselves.”

Ki-67 is used to determine tumor growth in several types of cancer including breast cancer, says Dr. Ruth O’Regan, chair of the department of medicine at the University of Rochester in New York. 

“We use it to determine the type of breast cancer a patient has, which helps us make treatment decisions,” O’Regan notes. “It’s commonly used in cancers that express estrogen receptors, which makes up about two-thirds of the breast cancers that we treat.”

Ki-67 has been used to determine the rate of tumor growth for many years, but there have been issues around the consistency and reproducibility of clinical scoring of Ki-67 levels. However, using more automated technology to read scores and consensus meetings of the experts in the area have led to more widespread acceptance.

The protein was given a boost in October 2021 when the Food and Drug Administration (FDA) approved Verzenio (abemaciclib), a CDK4/6 inhibitor, with endocrine therapy for adjuvant treatment (additional therapy given after primary treatment to lower the risk of the cancer returning) of adults with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)- negative, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score of 20% or greater.

“This was a game changer because it was the first FDA approval of a CDK4/6 inhibitor in the curative setting, notably after this class of drugs had dramatically improved outcomes when added to hormone therapy for metastatic breast cancer,” observes Dr. Heather McArthur, an associate professor in the Department of Internal Medicine at UT Southwestern Medical Center in Dallas. 

“It’s hugely impactful to have the addition of a CDK4/6 inhibitor in our arsenal of drugs for early-stage breast cancer.”

The efficacy of Verzenio with endocrine therapy was evaluated in monarchE, a multicenter clinical trial that included women and men with the above-described form of early breast cancer with a high risk of recurrence. 

Patients received either two years of Verzenio plus their physician’s choice of standard endocrine therapy or standard endocrine therapy alone. 

In patients with high risk of recurrence and a Ki-67 score of 20% or greater, the trial showed a statistically significant improvement in invasive-disease-free survival (the time after treaatment that a patient survives without signs of cancer) among the cohort receiving Verzenio.

Ki-67 levels are usually scored at the time of diagnosis. When a tumor is biopsied, a small sample is stained through a process known as immunohistochemistry, which reveals the cells expressing Ki-67. 

In some labs, pathologists examine the slide and estimate the number of cells rather than actually count them, notes Dr. David Rimm, a professor in the department of pathology at Yale University School of Medicine in New Haven, Connecticut. 

“Some would only count a few cells, and some would count more because the more cells you count, the more accurate you are, though it takes more time,” he explains. “So there was a sort of tension between accuracy and efficiency for reading this test.”

For breast cancer, a Ki-67 score of 5% or less is considered low, and greater than 30% is considered high. 

“Those are the cutoff points at which we can have great concordance among pathologists, and the International Ki67 in Breast Cancer Working Group also recommends those cut points,” says Rimm.

The FDA’s approved cutoff point for the use of Verzenio is 20%, which could result in different interpretations among pathologists. 

“The maker of (Verzenio) didn’t take that into account when they designed their cut point,” Rimm says. “There are laboratories that still use a cut point of 12%, 13% or 14%, which is what led to the problems of nonreproducibility in the first place. It’s tough for pathologists to be really reproducible in that range, even counting every cell.”

In response, the American Society of Clinical Oncology and the National Comprehensive Cancer Network issued their own recommendations for consideration of Verzenio in high-risk patients, says McArthur, although their recommendations were agnostic of Ki-67 and did not include a cutoff.

“Those decisions were made based on a variety of reasons, namely the fact that not every cancer center performs Ki-67 testing, that Ki-67 has been a notoriously unreliable biomarker with a lot of interobserver and interlab variability, and uncertainty as to the optimal cutoff for determining high-versus-low scores,” McArthur notes. 

“It’s a test that’s been fraught with challenges over the years, and it was interesting that the FDA decided to include the 20% cutoff in their approval.”

Concern over the accuracy of Ki-67 scoring may also result from the inherent heterogeneity of tumors, adds Rimm. 

“Even though we can measure the amount of Ki-67 relatively accurately, we’re only sampling a tiny piece of the tumor,” he explains. “When we make a diagnosis of cancer, we sample less than 1% of the tumor, so if proliferation is heterogeneous (varies by location), it might be inaccurate or only represent part of the tumor.”

As medicine moves into the era of digital pathology, automated approaches to scoring Ki-67 are becoming more commonly accepted, Rimm notes. 

“I led the work by the (International Ki67 in Breast Cancer Working Group), which showed that an automated assessment was as good or even better than the assessment by counting pathologists,” he says. “However, we didn’t want to require automated assessment because there are still sites that don’t have the machinery to do it.” 

UT Southwestern is among the institutions that do not use automated assessment to score Ki-67 in breast tumors, although it does see it more consistently in outside reports, says McArthur. 

“We typically repeat all biomarkers in-house to ensure that our breast cancer-dedicated pathologists agree with outside interpretations, especially when they are automated,” she adds. “We are pretty rigorous in confirming those results within our breast cancer-dedicated pathology service.”

A tumor’s Ki-67 score helps establish the rate of tumor growth, but its influence in developing treatment options often depends on the oncologist in charge, says Dr. Joseph Geradts, a clinical professor in the department of pathology and laboratory medicine at the East Carolina University Brody School of Medicine in Greenville, North Carolina.

“The oncologists at (East Carolina University) usually make treatment decisions in the absence of a Ki-67 index, and that’s true for many oncologists around the country,” he explains. 

“This is because they already have a lot of information that allows them to make treatment decisions, such as the routine pathology report, which includes the tumor grade and mitotic index, both of which are correlated with the Ki-67 index, and other assays such as Oncotype DX. It’s a relatively small group of patients for whom Ki-67 adds a lot to what is already known, though there are oncologists who rely on it more heavily.”

In addition to helping determine the rate of tumor growth at diagnosis, Ki-67 expression can be a useful monitor of tumor response to preoperative endocrine therapy. 

“In many cases, preoperative endocrine or chemotherapy is very effective, but sometimes it is not,” Geradts says. “That’s where Ki-67 comes in because it has been shown that in those tumors where the Ki-67 index goes down after treatment, the patient benefits from that therapy. That’s another area where Ki-67 has proved useful, but admittedly, it’s a relatively small percentage of patients.”

Although Ki-67 may play a minimal role in deciding treatment for some patients, an extremely high Ki-67 score can be quite determining for others.

Megan-Claire Chase of Dunwoody, Georgia, had her treatment influenced by a high Ki-67 score. After months of unusual symptoms followed by the discovery of a hard lump in her left breast, Chase was diagnosed in September 2015 with stage 2 invasive lobular breast cancer. 

Through her own research, Megan-Claire Chase navigated conflicting opinions about her Ki-67 score and knew she made the right decision about her breast cancer treatment.

Her treatment regimen included 16 rounds of chemotherapy (Adriamycin PFS [doxorubicin hydro- chloride], Cytoxan [cyclophosphamide] and Taxol [paclitaxel]), 33 rounds of radiation, and a lumpectomy, reduction and reconstruction.

“The biopsy of my tumor showed that I was ER (estrogen receptor) positive (95%), PR (progesterone receptor) positive (99%), HER2 negative, and my Ki-67 score was 60%,” says Chase, who is the breast cancer program director at SHARE Cancer Support. 

“With that plus genetic counseling, my family history and the fact that I had an unknown variant, my oncologist felt it was important to give me the motherload of chemotherapy to kill everything.”

As she entered the survivorship phase, Chase chose another oncologist, who shocked her by telling her that he wouldn’t have recommended chemotherapy even with her high Ki-67 score. 

However, Chase did her own research and realized that her Ki-67 score and other factors made her an ideal candidate for the treatment she received. 

"The chemo was supposed to, first, contain my tumor from spreading, and then shrink it as much as possible, and that’s what it has done,” she states.

Unlike Laseter, Chase was unfamiliar with Ki-67 at the time of her diagnosis. 

Intent on understanding as much as possible about her cancer, she questioned the reasoning behind her recommended treatment regimen. 

“I asked, ‘Why are you giving me this? Is this a cookie-cutter treat- ment?’ And I was told no. It was based on several factors, including my Ki-67 score of 60%,” Chase says.

Although the FDA approval of Verzenio with endocrine therapy 

for early breast cancer put a new spotlight on the role and value of Ki-67, most pathologists believe the approval was a one-off that won’t lead to significantly greater use within cancer pathology. 

Of greater interest are technologies that make Ki-67 scoring more reliable and less subjective.

“I believe an automated way of measuring Ki-67 will be important because it takes the subjectivity out of the measurements,” says O’Regan. “But honestly, more and more, we’re moving toward looking at genes rather than proteins in terms of what drives cancer. So it may be that how proliferation is measured will be completely different than what we do now.”

Geradts also believes that digital image analysis is the way of the future, noting, “Ki-67 is very much observer dependent, and that can be eliminated by using computer algorithms. As these algorithms become more commonplace and affordable, we’ll likely see an increased number of laboratories that will choose to quantitate Ki-67 because it will be much more reproducible.”

It all makes for a very exciting time to be treating breast cancer, says McArthur.

“We have had in recent years an unprecedented number of FDA approvals that have had a huge clinical impact in terms of decreasing risk of developing metastatic disease for patients with early-stage breast cancer and improving overall survival for patients who do have metastatic breast cancer,” she says. 

“We want to learn more about cell proliferation and other factors so that we can offer more effective treatments to patients who need it and optimize treatment recommendations for those who can achieve those same great outcomes — but with less toxicity in the form of fewer drugs.”

To learn more about Kate Laseter's journey with stage 2 invasive ductal carcinoma and using her experience as an employee at a breast cancer research facility to push back against doctors who minimized her ultrasound findings,

 listen to this "Cancer Horizons" podcast episode

An FDA approval put Ki-67 scoring — which may predict tumor growth — in the spotlight, but what that means long term to patients depends on who you ask. 

Will There Be a Resurgence of Ki-67 Scoring in Breast Cancer?

What do you do when your professional training tells you that something might be off with your body, but your doctors disagree?

Kate Laseter used her experience as a histology technician — someone who is trained to turn tissue samples into microscopic slides for a pathologist to read for research or diagnostic purposes — to advocate for herself during her journey with HER-2 positive stage 2 invasive ductal carcinoma, a type of breast cancer. 

That’s the position Kate Laseter found herself in last August. As a histology technician — someone who is trained to turn tissue samples into microscopic slides for a pathologist to read for research or diagnostic purposes — Laseter was very diligent with her health. And since she worked for a lab in Golden, Colorado, that specialized in breast cancer research, she noted she was diligent with self-breast exams. She was also well informed about Ki-67, a protein that is expressed when tumor cells divide. A high Ki-67 index indicates aggressive tumor growth. The median Ki-67 score is 15%.

After finding a lump, she tried to get a mammogram but was denied due to her age (she was 29 at the time). When doctors dismissed the findings of her ultrasound and said to wait three to six months to get a biopsy, Laseter had to fight to get it done right away. Eight weeks after finding the lump, Laseter was diagnosed with HER-2 positive stage 2 invasive ductal carcinoma with a grade 3 histological score and a Ki-67 score of 65%.

Of note, grade 3 histological score indicates abnormal cancer cells that may spread more aggressively. After receiving chemotherapy and a double mastectomy, she was declared cancer-free in March 2022.

In today’s episode of the “Cancer Horizons” podcast, the 30-year-old Thornton, Colorado, resident shares her cancer journey, how her job as a histology technician helped guide her through her diagnosis and treatment, the important role Ki-67 scores can play in breast cancer treatment, the significance of self-advocacy as a patient with cancer and more.

For more news on cancer updates, research and education, don’t forget to 

To learn more about Ki-67 scoring and how it can affect patients with breast cancer, check out this 

article featuring interviews with patients and experts

Podcasts

A woman with stage 2 invasive ductal carcinoma — a type of breast cancer that begins in the milk ducts of the breast — shares how her experience as an employee at a breast cancer research facility helped her push against doctors who minimized her ultrasound findings and how her Ki-67 score informed her treatment choices. 

A Patient With Breast Cancer Explains How Her Job Saved Her Life

As a retired urologist, Mark Samberg, 72, of Sacramento, California, was familiar with what would happen after receiving a prostate cancer diagnosis in 2020.

The advantage he had was better understanding his diagnosis, treatment and what came with it.

The disadvantage was knowing what might happen to him.

Because of his career as a urologist, Mark Samberg was quite familiar with the concept of oligometastatic prostate cancer.

“Being a physician, you know the right questions to ask,” he says. “The bad part, of course, is that you’ve already seen the end of the book a few times, how the story could possibly end. That’s the scary part.”

One portion of his diagnosis he was familiar with was that his disease was in an oligometastatic setting — a sort of intermediate state that is more advanced than locally-confined disease but is not yet full-blown metastatic disease — a state that many patients may not know even exists.

There is renewed interest in and growing clinical evidence of an “oligometastatic” state. Patients with oligometastases have a low volume of metastatic disease and limited sites of involvement and can experience prolonged disease-free intervals and possibly even improved overall survival through a combination of systemic and local therapies such as chemotherapy and radiation. An important aspect of this definition is that local therapies could feasibly be used to remove or eradicate areas of disease that are visible by scanning techniques and that medical therapy could address microscopic cancer that is not easily discernable.

The concept of an oligometastatic state was proposed in 1995 by oncologists Samuel Hellman and Ralph Weichselbaum, and prostate cancer, because of its long natural history and high prevalence, has become an important focus of research investigating the potential value of more precise treatment for oligometastatic disease.

“The oligometastatic hypothesis suggests that there may be patients who have disease spread to other parts of the body, but if we are very focused about treating them, we may be able to get all of the cancer or at least help the patient do better for longer and keep some of the medical approaches available for later,” explains Dr. Ryan Phillips, a radiation oncologist at Mayo Clinic in Rochester, Minnesota.

“The reason to appreciate that it exists is we can better tailor the treatment to the individual.”

According to Dr. Neha Vapiwala, professor and vice chair of education, radiation oncology, at the University of Pennsylvania in Philadelphia, oligometastatic prostate cancer has traditionally been defined by the detection of one to five metastatic sites on conventional imaging, such as CAT scans, PET scans, MRI and technetium bone scans.

“In years past, using the conventional imaging technologies that were available, if we saw up to five lesions, the thinking was that this patient’s disease might have a different natural history than someone who presents with many more lesions,” Vapiwala notes. “We might be able to intervene with treatment that’s more aggressive, targeting the handful of lesions that are seen, usually in addition to the normal systemic therapy we would give, with the idea of reducing tumor burden and, ideally, prolonging progression-free survival. But the ‘quality’ — meaning location and type — of metastatic disease also matters, not just the quantity. And this upper limit of five may not remain relevant as we learn more through molecular imaging.”

Vapiwala says there are essentially two medical camps regarding the aggressive treatment of the prostate gland, if not yet treated, and/or sites of metastatic disease, and its role in enhancing survival. One side believes that while new imaging technologies detect small lesions earlier and more accurately, allowing for safer treatment, ultimately nothing changes regarding overall survival.

“Then you have individuals who say no, it’s not just simply iatrogenic (relating to illness caused by medical examination or treatment) stage migration; we’re not just diagnosing them earlier, but because we’re intervening, we’re making an impact,” Vapiwala says. “And some of these aggressively treated patients do have a robust treatment response or at least remain on a protracted course, and do not inevitably develop explosive disease later. This supports the idea that this is a different phenotype, a different biology altogether.”

The most common metastatic sites for prostate cancer are lymph nodes and bones, and this was true for Samberg, who was found to have lesions on his lumbar spine and scapula, as well as some lymph nodes, following a diagnosis of prostate cancer.

Samberg’s cancer journey started in 2019 when he began experiencing more frequent urination and other symptoms indicative of benign prostatic hypertrophy despite an active, healthy lifestyle. In early January 2020, he visited a colleague who told him his rectal exam was abnormal and referred him to a specialist at the University of California, San Francisco. By then, his prostate-specific antigen (PSA) level had progressed from 1.7 to 3.8 (the normal range is between 1.0 and 2.5).

Samberg underwent an MRI in February 2020, which he found concerning. A biopsy was scheduled, then everything shut down because of COVID-19. Months later, Samberg finally received his diagnosis and a Gleason score of 4+4, which is considered high-risk disease. Imaging during his pretreatment work-up revealed the metastases. Samberg’s treatment included androgen deprivation therapy with leuprolide, stereotactic body radiation, radiation to the metastatic sites and several cycles of Keytruda (pembrolizumab) as part of a clinical trial.

Because of his work as a urologist himself, Samberg was familiar with the concept of an oligometastatic state.

However, this was not the case for Chuck Pappas, 72, of Plymouth, Minnesota, whose prostate cancer journey involved three separate incidences over a course of several years. A rise in his PSA heralded each new bout, suggesting metastases that were later confirmed via imaging. Pappas underwent prostate surgery, stereotactic body radiation and combined treatment with radiation and leuprolide. He was declared cancer free in May.

His care team at Mayo Clinic in Rochester, Minnesota, never used the phrase “oligometastatic disease,” Pappas says, likely because he was a layman.

“But I believe that’s what I had because when they first started my radiation treatment, they found a few lesions, which later progressed to my lymph nodes,” he observes. “Looking back, it certainly fits.” 

Oligometastatic disease is most effectively diagnosed through imaging, which is more sensitive today than ever before. One of the most effective new technologies is prostate-specific membrane antigen (PSMA) PET imaging, which has been available in Europe and Australia for several years and received U.S. Food and Drug Administration approval in 2021. This is the imaging technology that revealed Samberg’s metastases.

Chuck Pappas says he believes he had oligometastatic prostate cancer because when he first started radiation treatment, oncologists found a few lessions that later progressed to his lymph nodes. 

“PSMA PET imaging has been a big game changer for us because it allows us to diagnose metastatic disease much earlier,” says Dr. Peter Carroll, professor of urology at the University of California, San Francisco in the department of urology. “It has shown that when we do that, we change treatment recommendations substantially. In the past, we might have given radiation or hormonal therapy alone. Now, with earlier detection, we’re offering treatments like stereotactic body radiation with or without hormonal therapy or surgery for metastatic disease. What we don’t know yet is how that translates to long-term disease-free survival.”

Samberg said he was grateful to receive PSMA PET imaging.

“My metastases likely would not have been detected under our standard work-up regimen,” he said. “In fact, they did the standard imaging and didn’t see the lesions that the PSMA PET scan showed.”

Equally exciting is the choline C-11 PET scan, which uses a radioactive form of the vitamin choline as a tracer to help detect sites of recurrent prostate cancer. This is the technology that revealed Pappas’ nodal metastases. A low-dose CT scan is commonly done at the same time to help further show internal anatomy, the Mayo Clinic reports.

Older imaging technologies, while not as sensitive, still have value, Vapiwala observes.

“MRI can still be very useful, in particular, MRI of the pelvis,” she notes. “There are also centers around the world that are very focused on whole body, or multiparametric MRI. In many places technetium scans remain standard for evaluation of the bony skeleton. But increasingly we’re seeing PET imaging supplementing if not replacing these scans for staging and clinical decision-making.”

The American Society of Clinical Oncology, in a report titled “Approach to Oligometastatic Prostate Cancer,” advises a multimodal treatment approach to patients with oligometastatic disease “with evidence for surgery, radiotherapy, and systemic therapy, alone or in combination, improving patient outcomes.”

Androgen deprivation therapy (ADT), in which the patient’s testosterone level is lowered in an attempt to hold the cancer in check for as long as possible, has proved especially effective, notes Phillips.

“There are other complementary medications, including more advanced androgen-directed therapies, that can make this approach last longer and be more effective,” he adds. “What we’re learning more and more is that for patients who have a limited number of detectable areas of spread, being more aggressive in treating those areas can add a lot of value and help patients live longer. The way we do that, most commonly, is with targeted radiation. There are also times where we use surgery or other ablation techniques such as radio frequency ablation or cryotherapy.”

Prostate cancer in the oligometastatic setting has been a topic of study for several years as researchers seek to better understand the disease and develop more effective diagnostic imaging technologies and treatment.

“There are some big questions around oligometastatic prostate cancer, and I believe we have the answers to many,” says Carroll. “The first is, can we diagnose this disease state better than we had in the past? And the answer is yes. We’re clearly seeing that when we diagnose it earlier, we’re changing treatment recommendations based on historical paradigms in imaging. So we’re diagnosing it more commonly and treating it differently. The big question is. Are the outcomes any better? How many quality-adjusted life years will it add? That remains to be determined. My feeling, based on the evidence to date, is that it will be beneficial. What I don’t know is the magnitude of that benefit or the financial cost.”

Vapiwala hopes to add to that discussion through the ongoing national phase 3 randomized INDICATE trial. Patients with rising PSA after prostatectomy and no evidence of metastases on conventional imaging all receive standard of care pelvic RT and short-term androgen deprivation but are randomly assigned based on their baseline PET scan finding to local therapy intensification with metastasis-directed RT if they have PET-positive disease outside the pelvis or system therapy intensification with apalutamide if they are PET-negative outside the pelvis.

“We’re asking, if we find disease on PET only and make treatment decisions based on that, are we making a meaningful difference in clinical outcomes?” Vapiwala asks. “If we see a few lesions and chase after them, it might make us feel better, but are we actually helping the patient?”

Other areas of research opening doors include the following:

Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer,” published in 2020 in the 

Journal of the American Medical Association

, found stereotactic ablative radiotherapy promising for men with recurrent hormone-sensitive oligometastatic prostate cancer who wish to delay the start of ADT.

Researchers at the University of Florida are evaluating the outcomes of patients treated with an investigational radiation regimen using stereotactic radiotherapy for oligometastatic prostate cancer, and to establish efficacy and safety.

Mayo Clinic is collaborating with Johns Hopkins University on research looking at oligometastatic prostate cancer treated with targeted radiation with or without the addition of a bone-specific radiopharmaceutical. “It’s an infusion of radium, which goes to areas of bone disease and may treat microscopic spread in the bones that we can’t yet detect,” reports Phillips.

Thanks to recent advances in diagnosis and treatment, the risk that oligometastatic prostate cancer will eventually become terminal is far less than in years past, oncologists say. 

“All men who have metastatic disease are at risk of dying from it,” notes Carroll. “I believe the key for many is to turn prostate cancer from a lethal disease to a chronic disease. That’s what we’re trying to do.”

“I believe the key for many is to turn prostate cancer from a lethal disease to a chronic disease. That’s what we’re trying to do,” says an expert at the University of California, San Francisco.

Don Vaughan

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