Active Surveillance Takes Center Stage at GU Cancers Symposium

Active Surveillance Takes Center Stage at GU Cancers Symposium

Dr. Laurence Klotz
The 2017 Genitourinary Cancers Symposium began with a session highlighting current research into active surveillance (AS) for prostate cancer. Experts discussed differences in active surveillance guidelines in Canada, the United Kingdom, and the United States and how genomic tests and imaging play a role in this disease management strategy. ProtecT study data were also discussed, and a new study was presented that identified dozens of new prostate cancer susceptibility loci.

Though AS has become a mainstream treatment option in much of the world, guidelines on its use do still vary somewhat from country to country. Laurence Klotz, MD, CM, of Sunnybrook Health Sciences Centre at the University of Toronto, spoke about some of the differences in those guidelines, and noted that in 2016 ASCO endorsed the Cancer Care Ontario guidelines, although with some qualifying statements.

Dr. Klotz noted that among the key differences between those and the U.K.’s National Institute for Health and Care Excellence (NICE) guidelines involve the use of ancillary tests beyond digital rectal exams, prostate-specific antigen tests, and biopsy; a clear role for 5-alpha-reductase inhibition, which Dr. Klotz said is not a particularly key element to therapy today; and the recommendations regarding MRI imaging. “Guidelines may lag behind in a rapidly evolving field, so these are not the final word on this story,” Dr. Klotz said.

Imaging and biomarkers

Two remaining questions involve the use of imaging and of molecular biomarkers. The NICE guideline is the only one that specifically emphasizes the use of multiparametric MRI. Shonit Punwani, BSc, PhD, MBBS, of University College London, spoke about the use of MRI in AS, and said its primary benefit is found when used before a biopsy to help localize the disease, “so that we can find where the tumor is, and we can put a needle in it.”

Dr. Lorelei A. Mucci
Multiparametric MRI can be used before enrollment into AS and can help guide which patients to enroll. “You need to know where you’re starting if you’re going to [use] AS,” Dr. Punwani said. A key outstanding question, though, involves definitions of disease progression on this imaging test, and quantitative metrics are still needed to help answer that question.

Regarding molecular biomarkers, Lorelei A. Mucci, MPH, ScD, of the Harvard T.H. Chan School of Public Health in Boston, said that three tumor genomic tests are currently available. She said that clinical factors used to guide men into AS have good sensitivity in predicting bad outcomes, but perhaps lower specificity. A biomarker test should perform better than Gleason scoring and other clinical information in terms of predicting long-term disease-free survival. In AS, it would be ideal to have biomarkers that could classify men who have virtually no risk of developing metastatic disease or prostate cancer–specific mortality.

A new study presented during the session will help move the biomarker field ahead. Rosalind Eeles, PhD, of the Institute of Cancer Research in the United Kingdom, presented results of a meta-analysis aimed at identifying novel prostate cancer susceptibility loci (Abstract 1). She pointed out that more than 100 genetic variants have been linked to prostate cancer risk, but there are currently no known common “aggressive” disease markers. Previous work has suggested that 5% to 6% of familial relative risk (FRR) is linked to rare variants, 26% to common variants, and 68% remain unexplained.

Dr. Eeles and colleagues conducted a genome-wide association study, and combined it with several previous such studies in a meta-analysis. In total, they included 82,308 cases and 61,074 control patients; 15,773 cases were considered aggressive. Dr. Eeles and her colleagues identified 65 novel susceptibility loci; the new variants account for about 6% of the FRR, leaving 62% still unexplained.

Among these loci were two single-nucleotide polymorphisms that act as markers for early-onset prostate cancer (55 years or younger at diagnosis). Four SNPs were associated with aggressive and indolent disease, although none specifically with aggressive disease alone.

Dr. Eeles said that if these results were used to type everyone in the room, the top 1% would have a 5.72-fold increased risk of prostate cancer. The bottom 1%, meanwhile, has “a very low risk indeed,” with a 0.17 relative risk compared to the middle 50% of the population.

ProtecT Study

Obviously, understanding the outcomes with AS as compared to other treatment options is a crucial piece to determining which patients should follow this route. Freddie C. Hamdy, MD, FRCS, FMedSci, of the University of Oxford in the United Kingdom, spoke about the ProtecT study, results of which were published in October 2016 in the New England Journal of Medicine.

[Read: Surgery, Radiation, or Active Surveillance? Findings From the ProtecT Trial for Prostate Cancer]

ProtecT included 1,643 men with prostate cancer randomly assigned to receive active monitoring, surgery, or radiotherapy. Neither prostate cancer–specific nor overall survival were significantly different at 10 years between these groups, although rates of disease progression and metastasis were higher in the active monitoring group than in the other two treatment groups.

Patient advocate Howard Wolinsky (left) after his presentation at the 2017 GU Cancers Symposium.
Dr. Hamdy noted that there were also no differences with regard to quality-of-life measures between the groups, which he said came as some surprise. “I have a hypothesis about this: It isn’t so much what we give to the patients as a treatment, it has more to do with the diagnosis of cancer,” he said. “We give these patients a new passport for life, they become ‘cancer patients,’ and that is what affects their quality of life more than anything else.”

For the first time at a GU Symposium, the panel also included a patient representative in order to provide some of that human perspective. Howard Wolinsky, MS, a long-time reporter for the Chicago Sun-Times and a lecturer at Medill School of Journalism at Northwestern University, volunteered his case history, which was discussed throughout the panel session. After an initial diagnosis in 2010 he went on AS, and has since had several negative biopsies and seen his PSA rise and then decline again to near-baseline levels.

[Read: Navigating the Waters of Active Surveillance: A Patient’s Story]

Mr. Wolinsky said that though he opted for AS, “it was a choice that I nearly didn’t have.” Although this may have improved in the years since, he said he had to switch doctors before AS even became a possibility. He also suggested that clinicians should think more about the human aspects to treatment, and that some clinicians he interacted with were dismissive of questions about genetic testing, among other issues.

“I think there still needs to be a lot of education, and maybe some hand-holding, with some patients,” Mr. Wolinsky said, noting that as a reporter who covered health care he likely had done much more homework than an average patient. “Patients are people, they’re not as sophisticated as you are, about how it works,” he said. “You need to do a better job of explaining it.”

– David Levitan