Dr Yuh on the Role of Genetic Factors in Risk Stratification for Prostate Cancer

Bertram Yuh, MD, MISM, MSHCPM, professor, Division of Urology and Urologic Oncology, Department of Surgery, director, the Urologic Oncology and Robotic Surgery Fellowship, associate chief medical information officer, clinical documentation and analytics lead, City of Hope, discusses the role that genetic factors, such as 

 mutations, play in the risk stratification of patients with prostate cancer.

The field of genetic assessment in prostate cancer is developing and holds significant potential, Yuh begins. Prostate cancer is highly heritable, making genetic testing an important tool for gathering crucial information, he says. Prostate cancer tends to cluster in families, so assessing family history of cancer is key when evaluating a patient, Yuh explains, adding that DNA damage repair mutations, especially in 

, increase the risk of developing prostate cancer, particularly in the context of these mutations. Therefore, people with a family history of breast, ovarian, or pancreatic cancers should consider genetic testing and counseling, he expands. 

 mutation carriers face a higher risk of developing prostate cancer andtend to present with more aggressive disease characteristics, such as higher grades and advanced stages of disease, which are associated with poorer survival outcomes, Yuh reports. Additionally, prostate cancer, as well as colorectal cancer, are linked to Lynch syndrome, he notes.

When patients with prostate cancer are found to have genetic mutations, this information can guide family members toward genetic counseling or testing, offering broader insights for the family, Yuh continues. He adds that the research into the influence of genetic factors on treatment decisions is ongoing. At present, the greatest effects of genetic testing in prostate cancer appear to be in later-stage disease, he emphasizes. However, genetic testing shows considerable promise in improving disease prognosis and informing treatment decisions, Yuh reports. At City of Hope, Yuh and colleagues recommend routine genetic testing for all patients diagnosed with prostate cancer to identify relevant mutations.

Videos

Bertram Yuh, MD, MISM, MSHCPM, discusses the role of genetic factors, such as BRCA mutations, in the risk stratification of patients with prostate cancer.

Bertram Yuh, MD, an assistant clinical professor of Urologic Oncology and a urologic oncology surgeon at City of Hope, compares the outcomes with surgery and radiation treatment in patients with localized prostate cancer. Yuh shared this insight in an interview during the 2016 

 State of the Science Summit on GU Cancer.

It is very difficult to compare radiation therapy and surgery in a clinical trial, Yuh explains. This is because, he adds, it is challenging to tell a patient they are going to undergo surgery instead of radiation therapy, or vice versa.

Because of this, Yuh observed that patients who undergo surgery have different characteristics than patients who undergo radiation treatments. Although it is difficult to compare them both side by side, he adds that both treatments are effective and play a major role in the management of patients.

There may be certain patients who would be better served by 1 treatment or another, depending on their individual biases. Additionally, there are some patients who may be against surgery or radiation therapy, for example. Therefore, it is important for oncologists to be aware of patient preferences.

Bertram Yuh, MD, an assistant clinical professor of Urologic Oncology and a urologic oncology surgeon at City of Hope, compares the outcomes with surgery and radiation treatment in patients with localized prostate cancer. Yuh shared this insight in an interview during the 2016 OncLive State of the Science Summit on GU Cancer.   

Dr. Yuh on Outcomes Between RT and Surgery in Prostate Cancer

When prostate cancer metastasizes, the propensity is for the disease to follow the drainage of the prostate through pelvic lymphatic channels. Unfortunately, the pelvic lymphatics on an individual basis are variable, and radiographic imaging and functional tests have yet to show significant sensitivity for detecting lymph node disease. As such, current surgical practice is to perform lymph node dissection (LND) in patients who are at higher risk of harboring disease in the lymph nodes.

The past decade has demonstrated a movement toward more extensive LND in order to sample and remove more lymph nodes. Studies have shown that a limited LND overlooks a large number of nodes, and the 

 and National Comprehensive Cancer Network guidelines suggest performing an extended LND if an LND is to be done at all. The enthusiasm for a more aggressive extended LND needs to be balanced against possible risks, in order to avoid harm to the patient. The number of lymph nodes removed has been used as a surrogate for LND quality, though the actual template followed is likely of more significance. Experienced surgeons are more likely to perform extended LND, as this involves delicate dissection around major pelvic blood vessels.

Recent regulatory recommendations have advocated against PSA screening to reduce overdiagnosis and overtreatment, and has been a topic of major debate. However, a product of reduction in the use of PSA screening may be a stage migration toward more patients presenting with locally advanced and/or metastatic disease. The main advantage of extended LND is in staging these patients. As lymph nodes can be positive in >30% of high-risk individuals, the earlier detection of patients with N+ disease can allow for administration of adjuvant therapies, better assessment of prognosis, and enhanced ability for patient counseling. The ability to accurately assess the lymph node status at the time of surgery is an advantage of surgery compared to radiation treatment.

Another benefit of extended LND is the removal of micrometastatic disease that may in turn impact survival. In other malignancies, LND has been shown to confer a survival advantage. Using another urologic pelvic malignancy as an example, in bladder cancer the evidence for a survival advantage with extended LND is stronger. The oncologic benefit of extended LND in prostate cancer is unproven; however, several retrospective studies have shown an advantage to biochemical recurrence-free survival and cancer- specific survival.

At City of Hope, the urologic oncology team has 5 years of experience in robot-assisted extended pelvic LND at the time of prostatectomy, having performed the procedure in over 1,000 patients. The technique has continued to progress and is proven to be safe. We’ve demonstrated in several publications that the lymph node yield is increased compared to limited LND (from 7 to 22), nodal disease detection is improved (from 4% to 12%), and patients do not experience more complications. We have cared for patients with early lymphatic spread of cancer that remain cancer- free for a prolonged period of time after extended LND and no further therapy. Current and future enhancements will focus on refining dissection mapping using novel fluorescent and antibody- labeled techniques. In this way, we aim to discover which patients would benefit most, which patients may be spared LND, and which patients need a deliberately more thorough LND.

Extended LND removes more cancerous lymph nodes and optimizes the staging ability of prostatectomy. Patients may have one treatment opportunity to have these lymph nodes removed, and surgical treatment at a center with expertise in this procedure can offer that chance.

Articles

The past decade has demonstrated a movement toward more extensive LND in order to sample and remove more lymph nodes.

Bertram Yuh, MD

Articles

Dr Yuh on the Role of Genetic Factors in Risk Stratification for Prostate Cancer

Dr. Yuh on Outcomes Between RT and Surgery in Prostate Cancer

Tracing the Path of Prostate Cancer Spread