A new castration-resistant prostate cancer entity?

Feb 01, 2016

Urology Times SUO internship program member Brandon Manley, MD, reports on an SUO presentation highlighting several interesting findings on advanced prostate cancer with variant histology.

UT SUO 2015 Internship Member Profile

 

Dr. Manley is a urologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York. During the Society of Urologic Oncology 2015 winter meeting, he was one of several urologic oncology fellows to contribute articles to Urology Times through a collaborative “UT SUO Internship.” Urology Times extends its thanks to all of the fellows and the Society of Urologic Oncology for participating in this unique partnership. For other articles in this series, click here.

Washington-A presentation at the 2015 Society of Urologic Oncology annual meeting in Washington highlighted several interesting findings about advanced prostate cancer with variant histology.    

The presentation, titled “Intermediate Atypical Carcinoma: A New Castration Resistant Prostate Cancer (CRPC) Entity,” was presented by Eric Small, MD, of the University of California, San Francisco. Dr. Small leads a team of physicians and researchers called the “Dream Team” that is funded by the Prostate Cancer Foundation and Stand Up To Cancer. One of the team’s goals is to find new ways to improve the management of patients with metastatic and treatment-resistant prostate cancer.

Dr. Small described an emerging pathologic finding in many of the patients that he and his team study. About one-third of patients with CRPC in their study who have biopsies of metastatic lesions, have pathology that is different than typical adenocarcinoma, he reported. This entity has pathologic and genetic characteristics different than small cell or neuroendocrine carcinoma, which is one of the more common prostate cancer variants. They have given this pathology the name Intermediate Atypical Carcinoma (IAC).

Next: A “clinically very important subtype”

 

Dr. Small’s first point is that this group of cancers can behave and respond much differently than the more common metastatic adenocarcinoma, and he believes this is a “clinically very important subtype.” He presented data that showed that even when controlling for several other variables, patients with IAC have more “aggressive disease and shorter survival” compared to typical CRPC patients.

"More physicians are biopsying these patients [those with treatment-resistant CRPC] than in years past,” Dr. Small said, explaining one reason why this has become a somewhat new field of study. He added that the typical patient with variant histology behaves differently than other CRPC patients and commonly fails to have a rising PSA even in the face of clinical or radiologic progression.

Session chair Vivek Arora, MD, PhD, of Washington University in St. Louis, commented, “In circumstances where a classical neuroendocrine [NEPC] or small cell variant is suspected due to a lack of PSA production and the presence of visceral metastasis, it is often worth obtaining a biopsy if the patient is a reasonable candidate for platinum-based chemotherapy. If NEPC or small cell is confirmed, I think many would opt to treat those patients with combination therapy that includes a platinum [drug].”

Dr. Small postulated about the possible origin of IAC and said that while this disease may be histopathologically and genomically distinct from typical adenocarcinoma, it may represent a transition point from which some patients go on to develop small cell carcinoma or NEPC.

“We need to be careful not to suggest that AR [androgen receptor] targeting therapies are detrimental, as the clinical evidence unequivocally supports that the use of second-generation AR targeting agents clearly benefits patients with CRPC,” Dr. Arora said. “At the same time, there is no doubt that the use of highly effective AR targeting therapies affects tumor evolution and may be playing a role in the relatively frequent emergence of ‘intermediate carcinoma’ observed by Dr. Small and his colleagues.”

Dr. Small and his team, along with other groups, are continuing to study this new type of pathology along with other variant cancers in CPRC patients. They hope that, armed with more study patients and an expanding array of data, they will be able to better define and possibly treat these patients in the not-so-distant future.

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