Managing Patients With Multiple Primary Cancers

Part 1

Jue Wang, MD, UT Southwestern Medical Center, Houston, Texas, shares the case of a patient with 2 concurrent primary cancers: metastatic prostate cancer and metastatic colorectal cancer. Dr Wang highlights the importance of a multidisciplinary approach and biomarker testing when managing these patients.

Watch part 2 of this interview.

Transcript:

My name is Dr Jue Wang. I'm a professor of medicine at UT Southwestern Medical Center, a genitourinary oncologist taking care of prostate cancer patients. 

With our population aging, oncologists are increasingly encountering patients with multiple primary cancers, and this also contributes to our therapeutic response to the cancer. In cancer treatment, advanced patients live longer, they have a chance to develop more cancers. Another challenge is, in oncology, is increasingly sub-specialization. So the oncologist increasingly just focus exclusively on a narrow spectrum of cancer. Which leaves patients having to shift from one specialty clinic to another specialty clinic.

Basically, this is a challenge because our current cancer therapy is guided by the guidelines or clinical trial protocol study on those single cancers, which leave the community oncologist without guidance on managing those patients who present with 2 or more cancers. Now in 2025, this is not a rare phenomenon, it’s increasingly encountered. Our group had been studying this unmet clinical need. This article provides some insight into how we managed this challenging situation.

This is a gentleman within 2 or 3 months had 2 hospitalization and the diagnosed with 2 cancers: 1 colon cancer, 1 prostate cancer. Quite symptomatic, with a large tumor burden. The imaging showed lung and liver metastases at the beginning. Within 2 months when the doctors tried to figure out the biopsy, the cancer progressed, the lung lesions significantly increased, with numbers up to more than 100 cannonball-sized lesions, very, very atypical. Also, during the second hospitalization, the liver lesion also progressed. The patient become more anemic which led to the colonoscopy, and the findings of intraluminal colon mass biopsy showed colon cancer. The hospital’s doctor also did a liver lesion biopsy. They initially reported poorly differentiated carcinoma. The pathologist reached the conclusion this is a metastatic colon cancer. The patient was discharged to GI oncology to start on standard treatment for metastatic colon cancer. Of course, at a similar time, the patient also had overlapping symptoms, rectal pain, urinary tract symptoms, so Urology saw the patient at the emergency room. Because the PSA was moderately changed, just 6, mildly higher than the standard level, the urologist said we are going to do a biopsy in 1 month. When the patient entered into about 1 month of chemotherapy, the urologist got hold of the patient and did a biopsy which showed the prostate cancer. So, within 2 months, the patient got 2 cancer diagnoses, obviously staged metastatic setting. Obviously both quite symptomatic, large tumor burden. Patient is elderly, has multiple comorbidities including hypertension, diabetes, long-term diabetes, non-iscemia cardiomyopathy, low ejection fraction, has a pacemaker. And in second hospitalization patient actually had a stroke. So all those situations made the biopsy of a lung lesion become impractical. The interventional radiologist considered the patient’s cardiac reserve not able to handle the lung lesion biopsy at that time.

In summary, brief summary, we have this gentleman, we receive a consultation from our colleagues, the GI oncologists. We are GU oncologists. This gentleman already has a diagnosis of metastatic colon cancer. Now he has a newly diagnosed prostate cancer. In this situation we have an overlapping symptomology, a lot of symptoms. We have overlapping from the elderly patient with multiple comorbidities with the 2 cancer with 2 sites of large burdens of metastases, involving the lung and liver. The liver biopsy was initially reported as metastatic colon cancer. But 1 month later, the pathologist revised the pathology diagnosis because they have their own specialty conference. The GU oncologists looked at the prostate biopsy, they find 95% is regular, Gleason score 9, aggressive prostate cancer. But 5% showed a very poorly differentiated morphology. They compared this is a poorly differentiated group, they did all the immunohistochemistry sophisticated markers. They find a potential match with that liver poorly differentiated carcinoma. Therefore, they revise the diagnosis to metastatic- maybe this involves the liver, the prostate involved liver. In addition, pathologist showed ki67 proliferative markers are quite high, 90% consistent of very aggressive cancer.

So you have 2 cancers, both aggressive, both very symptomatic with large burdens. We now are facing a diagnostic dilemma, a challenge. Because the lung lesion we cannot biopsy and we don't know where it came from. The liver biopsy is complex. The colon mass biopsy is clear, colon cancer. The prostate cancer is mixed. It just shows with the standard pathology, advanced pathology morphology, immunohistochemistry, with advanced imaging, they cannot tell you 100% where those cancer come from. Sometimes, of course, cancer does not grow like a textbook. They do what they want. This is a unique, complex situation in the background of an elderly patient with multiple comorbidities. He just had a stroke during the second hospitalization. His wheelchair bound performance status is very borderline. That's the challenge we face every day, in community oncology.

How important was the multidisciplinary approach in this case?

Clinical trials do not- in general, they enroll patients with 1 single cancer, they exclude patients with multiple primary [cancers]. They simplify, looking for commonalities of patients. So there's no clinical guideline to guide the management of this treatment, but with our patients, there's this unmet need. As oncologists, we must work together to meet the challenge of this patient. Our result is a provide insight to that, with the facing this challenge with patients. We will use multidisciplinary approach. We involved multidisciplinary team early and we perform sophisticated pathological morphology, immunohistochemistry, molecular profiling. And we identify the patient’s prostate cancer actually harbored a mutation, BRCA2 mutation. We identified a vulnerability with that cancer.

In this situation, we are in an era where we're super-specialized. The GI oncology team recommended FOLFOX and based on the sophisticated finding, complex finding of that morphology that Ki67 of 90%, that poorly differentiated carcinoma involved the liver, GU pathology considered this a very, very rare subtype, although it's not a neuroendocrine, not small cell carcinoma prostate, but it is quite unique. The GU tumor board actually recommended another combination regimen: carboplatin plus cabazitaxel. In this patient we face 3 challenges: number 1, complex symptoms, overlapping symptomology; advanced cancer, large tumor burden, bottom-line performance status; the diagnostic challenges, very complex liver pathology, inability to biopsy the lung lesion int this situation, with the imperfect data and a lot of uncertainty. But this patient has large tumor burden, we have a very narrow window of opportunity to actually make a difference. Plus, in terms of therapeutic challenges, the patient has multiple comorbidities, meaning they have a less ability to handle the complex combination chemotherapy, let alone, in this case, if a super-specialty will recommend 2, doubled the combination regimen. There's no chance the patient will be able to handle this treatment.

What we did is we break down the wall of a super subspecialty. We are 1 team. We all serve 1 patient. Our goal is to help this patient. Our goal is not to follow rigidly the clinical trial guideline, because there's no clinical trial including 2 active stage 4 malignancies. There's no guideline to provide, but it is also not practical to try to fit the GI guidelines for metastatic colon cancer and the GU guideline onto 1 patient. What we did actually is utilize the multidisciplinary clinic, the wisdom.

The turning point of this case is really the pathologist relooking at the pathology. They identified the subpopulation of prostate cancer was similar with the liver pathology, that is really a testimony to our strengths as a multidisciplinary team. In this case the GU tumor board actually discussed this case 3 times. You can imagine how much time the team spent on this one unique case. We treated this as an “n of 1.” We utilized the precision medicine principle; we identified the vulnerability of the cancer. So, we decided, since patient cannot tolerate the 2 combination regimens together, we cannot afford to treat these 2 active cancers sequentially. We want to treat concurrently. We designed the regimen based on the oncology principle, based on the patient tolerability, patient on the patient's geriatric assessment.

We decided for first line treatment we are going to utilize FOLFOX combined with the androgen deprivation therapy. We used this regimen based on the findings that the prostate cancer has a vulnerability of DNA damage repair gene defect. DNA damage repair defects, such as BRCA2 mutation, will imply sensitivity to platinum-based treatment. We used 1 chemotherapy regimen, actually targeted to the tumor. We used a regimen conventionally used to treat metastatic prostate cancer, combined with the androgen deprivation therapy as a first line, we used this to act as “1 stone, 2 birds” strategy.

Within 3 months the patient achieved a concrete radiographic remission of the more than 100 lung lesions, totally disappeared. The liver lesions totally disappeared, at that time. We also explored whether we can use the dual PET scan strategy to differentiate these 2 tumors. We thought about utilizing the PET scan with FDG, to use different tracers, FDG, to detect metastatic colon cancer. We use PSMA tracer, to try to detect metastatic colon cancer. Based on the inability of interventional radiology not able to biopsy the lung, we tried to use a dual imaging strategy to clarify where the cancer came from. But when we did that, the cancer had already totally disappeared to our surprise. That was further confirmed by multiple CT scans. The patient remains in complete remission to today.

This publication, we want to show the multidisciplinary team involvement with the precision medicine principle, we are able to change the patient prognosis in an otherwise very difficult situation. The patient now, it appears we also improved his heart function. His heart function also improved to a normal ejection fraction. Now he's going to have a significant quality of life improvement without significant side effects. To go from wheelchair-bound for several months, now he's totally free and goes to the gym multiple times a day. That’s the short version of the summary of the story.

Watch part 2 of this interview.

Source:

Gray Z, Levonyak N, Liwei J, Ahn R, Balani J, and Wang J. Managing elderly patients with dual metastatic cancers — navigating diagnostic and treatment challengers. Oncologist. Published online: March 10, 2025. doi:10.1093/oncolo/oyaf026