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Hope Through Science

Have hope. Don’t despair. There are so many more options out there. We’re going to do everything we can.

Those are the words that kept Pat McGuire going through more than a few bouts with bad news. But he wasn’t always so hopeful. Pat has faced some dark days.

Pat should have been diagnosed much earlier than he was. He’d told his primary care doctor about a family history of prostate cancer. He’d had his prostate specific antigen (PSA) checked. It was 7.4 ng/ml, which is above a threshold of about 4 ng/ml that usually triggers action. But his doctor hadn’t mentioned that to Pat. More than a year and a half later, a new doctor told him that his PSA was elevated and that he should consult a urologist—which came as a surprise. A few weeks later, a biopsy revealed Gleason grade 7 prostate cancer.

Pat decided to have surgery. The lab results after his surgery showed Gleason 9 cancer that was extensive throughout the prostate and seminal vesicles. His next PSA was 17. Scans revealed metastatic disease, and he started taking Lupron as a first line of attack.

Initially, he struggled with this terrible diagnosis. “I was pretty low…..Nobody wants to find out they have metastatic prostate cancer—or any kind of cancer—and I felt I could have possibly [avoided] all of this if that one doctor had told me early on what my [PSA] number was and that I should see a urologist.” He wasn’t sure if he wanted to face the future if things got to a point where nothing could be done for him. Fortunately, his family—his wife Patti and two adult children—made sure he got the help he needed and kept him safe.

Here’s where Pat is very clear: “It’s important for people to know that during the darkest times, you can come out of it. There is hope. You can find good doctors, like I did at UW [University of Wisconsin] Hospital.”

Pat had tremendous trust in his treatment team. He started on a clinical trial—his first of three—of a DNA vaccine targeting the androgen receptor. This trial, led by Prostate Cancer Foundation (PCF) Young Investigator Dr. Christos Kyriakopoulos, aimed to (in Pat’s words) “kick start” his white blood cells into recognizing and attacking the cancer. Why a clinical trial instead of a more established treatment plan? Because Pat is also a scientist: he has a PhD in soil physics and is a retired environmental consultant. He recalls, “I knew I had an aggressive cancer that was spreading. It did not seem like traditional treatments were helping…..my best bet was get into clinical studies. The second reason was, I felt like I was contributing to science, if nothing else. I was committed to getting into any clinical study I could.”

About a year later, the cancer progressed and Pat switched from the clinical trial to enzalutamide. His pain was so bad that he also required radiation. Six months later, his PSA rose again. This time, he joined a new trial, funded in part by a PCF Challenge Award, led by Dr. Josh Lang at UW-Madison.

Dr. Lang is also Pat’s oncologist. Ever the scientist, Pat had been providing blood samples since the beginning of his cancer journey. Dr. Lang notes that in part because of his blood samples, and those of other patients, the team was able to discover a target called TROP-2 on the surface of prostate cancer cells anywhere in the body. The trial tested an antibody (IMMU-132) linked to a chemotherapy drug. When IMMU-132 attached to the TROP-2 on the cancer cells, the drug would be delivered to kill the cancer. This is an excellent example of translational research, Dr. Lang explains. “The type of research, where we study samples donated by patients, gives us a chance to find new vulnerabilities in each person’s cancer.” And, in Pat’s case, “It’s serendipitous that we were able to find something [in his blood sample], and we were able to bring that back to help him. It’s the reason I do this kind of research.”

Pat says the science was pretty complicated. What he remembers is his pain improved but there were side effects like losing his hair and feeling pretty wiped out. Dr. Lang recalls that Pat had a good response and “it allowed us to keep chemotherapy in the toolbox” rather than using it right away. But the cancer progressed again. At a family gathering on Memorial Day in 2019, Pat found that balance was compromised and walking was difficult. He called the clinical research nurse, who told him to go to the ER right away. It was a tumor pressing on his spine. He had surgery and radiation to his back to get rid of the metastases.

After progression on 2 trials and painfully aggressive disease, how did Pat gather the strength to motor on? He attributes it to his genuine connection to Dr. Lang. “I can’t say enough about Dr. Lang. About 2 years ago, I requested that I see him all the time. He’s a real ‘people person’ kind of doctor. He’s very positive, but also very honest. He tells me, ‘There’s new stuff coming up all the time; we‘re going to throw it all at you.’ That’s what I need. It gives me hope.”

Hope, combined with more science, finally yielded results for Pat. Once again, Pat had been donating samples, and as part of early work in another study, Dr. Lang had tested his genetics and found that he had a mutation in the BRCA2 gene. This was actually good news, because it meant Pat was eligible for a precision medicine clinical trial. This means that clinician-scientists were able to give him a drug combination that specifically targeted his specific type of cancer. He started on abiraterone and a PARP inhibitor, a new class of medications that interfere with cancer cells’ ability to repair themselves. Early work funded by PCF led to PARP inhibitors being tested in prostate cancer; two other similar drugs, olaparib and rucaparib, were approved in May 2020.

Pat knew it was working almost immediately. He had been on “a lot” of oxycodone for pain, and was able to quickly get off the pills. Initially, he hadn’t wanted to hear about his PSA—there had been so much bad news, and he didn’t want to follow it anymore. But after several months on the trial, Pat’s PSA decreased significantly. The research nurse called his son because she was so excited. Could she talk to Pat about it this time? “My PSA was dropping like a rock – it had been around 100, and now it’s slightly above 2.0 ng/ml.” He has had one significant side effect, severe shortness of breath, but that has largely resolved after decreasing the dose of the PARP inhibitor.

He also credits his family, including Patti, a retired nurse, and his two children (Colin and Devin), for helping him stay focused on what’s important. Patti has always tried to keep him in the present, rather than looking too far out at the “what ifs.” She noted, “When family members asked me what his prognosis was, I’d say, ‘Right now, he’s doing good.’ We don’t know what’s down the road….we’re not going into the rabbit hole; we’re staying in the moment.” In addition to his family, and Dr. Lang, Pat is grateful for the support of the entire UW Hospital Oncology nursing staff.

Pat is in a place where he can provide perspective to other men facing prostate cancer. Recently, he spoke with a friend of a friend who had just been diagnosed. “I told the guy, ‘Don’t lose hope, there is so much going on in this field. I was given 5 years to live—and I’m at 5 years now, and I’m still pretty healthy. I can still do things. I’m not dying. Stay calm until you know what the situation is. Even if it’s metastatic, there’s so much coming down the pike.’”