Managing Patients With Multiple Primary Cancers

Part 2

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.

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.

Can you discuss the use of biomarker testing for these cases?

Biomarkers really provide a significant role in the optimal management of these cases. Because regular clinical trials enroll patients with single cancer and quite a homogeneous population. For patients who present  with multiple cancers, 2 cancers, particularly in this situation 2 stage 4 cancers and both with a large tumor burden and quite symptomatic, we have a narrow time window to make a difference. Otherwise, if a patient deteriorates, nothing we do is going to help. So, we cannot use the “1 size fits all” approach to treat this patient, just like we treat a single cancer based on the clinical trial data. We need to look beyond what is obvious.

In this case, so the pathologists play a tremendous role. Number one, from morphology standpoint, the under microscope they can see, they can differentiate that 95% of prostate cancer is different from that 5% that poly different differentiated. You can see their expertise, the strength of the UT Southwestern Genitourinary Oncology Pathologist team. We oncologists always say pathologists are doctors’ doctors. They give this wake-up call. Then we look deeper into that.

In addition, the pathologists perform multiple markers. This is cancer from different sites. When they find the biopsy, the colonoscopy mass, the multiple markers that are consistent with the colon primary cancer. Then the prostate primary biopsy showed those common biomarkers, such as PSA, prostate acid, all those markers identify prostate primary. But they find how they identify that 5% different with that 95% of prostate population. They identify some other unique. Of course, they also identify the population that have a different ki67 proliferation index. And hey have different immune history chemistry markers, they have different morphology. Then the liver biopsy. Liver biopsy is the liver lesions. These needle biopsies are limited samples. Despite that limited sample, we did perform a comprehensive immunohistochemistry stain. It’s very difficult because like I alluded earlier, cancer does not grow according to pathology textbook. They're poorly differentiated. They have a different spectrum marker with the conventional prostate cancer.

Eventually we did a molecular marker. There’s a unique TMPRSS2-ERG translocation exists in the prostate cancer, not in other cancers. We can identify this is a prostate etiology. In addition, we also go deep into the molecular fingerprint. In every sample, so from the colon mass biopsy, prostate biopsy, liver biopsy —we tried, but the sample is too limited— later when the patient has a brain biopsy, we did a molecular fingerprint. The molecular fingerprint of the colon cancer showed typical mutation exists in the colon cancer. In contrast, the prostate cancer fingerprint and the brain metastases tumor fingerprint are different, consistent with prostate cancer markers. All those markers, in addition, we also identified the vulnerability of those cancers. Among all those molecular alterations, there's alteration called BRCA genes. We have a drug called BRCA PARP inhibitor. Actually this patient later was started on PARP inhibitor that with multiple layers of, with the guidance of biomarker, therefore we have multiple layers. We initially give him the chemotherapy which can target convert the effective in the DNA damage repair gene population. And later, guided by a molecular marker, that's the therapeutic subsequent regimen also guided by biomarkers. That’s the key of the success for management of this patient with sustained remission and long-term cancer control.

I think in the patient with multiple primary things, they are not fit into 1 particular guideline. You cannot use 1 protocol or 1 regimen to treat those patients. The solution likely we need to find some actionable biomarkers. Some vulnerabilities, where we have a drug we can attack exclusively, without needing to use those “one side fit for all” approach. This uses a smart approach, so we can maximize the clinical benefit and minimize the side effects.

What are the key take-aways from this case?

I will give a three takeaway of this study. So number one, is with the population aging, with the advanced cancer therapy, the challenge the oncologist face every day is of the multiple primary cancers,  is increasing. It is real and without a guideline. We need to leverage the multidisciplinary team expertise and really look at the cancer beyond the surface morphology, beyond the immunohistochemistry. Go down to the molecular fingerprint, looking for the vulnerabilities.

And the second takeaway is, because elderly patient have decreased tolerability to cancer treatment, they also have a lower physical reserve to diagnostic test. Hopefully we can develop some more of those non-invasive testing to help us identify those etiology sources of the multiple cancer, such as theranostic imaging, such as PSMA imaging, molecular imaging. We can differentiate different sources. We can identify tumors, different sources by molecular fingerprint, such as non-invasive liquid biopsy, circulating tumor cells. Identify those rare, atypical, unique mutations. This can help us meet the diagnostic challenge.

Number three, regarding the therapeutic challenges. It is not feasible, if the patient has 2 cancers, you cannot fit 2 individual single cancer guidelines onto 1 patient. Those guidelines are not supposed to apply to those patients. Actually, we need a call for oncology community to actually do more research on this population. This is a true unmet need. Randomized clinical trials are impossible, but “n of 1” clinical trials, such as this one, and the Rare Cancer Multiple Caner Registry, that's another way. Interdisciplinary collaboration is another way. I think our oncology community just needs to stand up, and meet the challenge of this situation. Because patients deserve patient-centered care, designing treatment based on their unique clinical situation, host situation, tumor situation, tumor vulnerability, is our duty. I think that's the takeaway.

In addition, I think one of the learning point from this case is, we know super-specialization provides more expertise, one oncologist exclusively becomes expert in one single cancer. But it also provides some obstacles. I had a patient this, a 92-year-old gentleman, had a pancreas mass initially. He worked with the pancreas cancer doctor for several weeks. Then the patient was sent to bladder cancer doctors, because now the biopsy showed bladder cancer. We leave patients with some frustrated experience, because super-specialization also leads to fragmentation of the care. At UT Southwestern Medical Center, we are advocates for patient-centered care in genitourinary oncology. We want to think what the patient needs.

The bottom line is we need to serve the patient. One of the first things we did is break down the super-subspecialty barriers. We integrated everybody into 1 team, to serve 1 team, serve 1 patient. The success is truly contributed to by multidisciplinary care integrating precision medicine, with patient-centered care in mind . And that's the way we meet the challenge of multiple primary [cancers] in the community.

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