New technology in imaging and genomic investigations have shed insights on disease diagnosis and progression, while at the same challenging standard medical strategies and prompting cancer specialists to re-think treatment approaches.
At the concluding session of the 8th European Multidisciplinary Meeting on Urological Cancers (EMUC16), experts took up active surveillance for early prostate cancer (PCa) within the context of new technology such as multi-parametric Magnetic Resonance Imaging (mpMRI), recent outcomes from genomic research and the impact of targeted treatment.
Chaired by Chris Bangma (ML) and Francesco Montorsi (IT), issues in active surveillance (AS) were presented by urologists Peter Carroll (USA), Laurence Klotz and Caroline Moore (GB), and pathologist Sara Falzarano (USA).
“The negative public pressure on PSA early detection may be tempered, but it will not go away,” said Carroll as he prefaced his lecture which surveyed the prospects and challenges in adapting AS as management option.
In clinical and translational research, Carroll said there is an increasing sense that prostate cancer is “a spectrum of disease influenced by host and tumour environment.”
“Active surveillance although increasingly recognized as a relatively safe option will be challenged by focal forms of therapy,” noted Carroll. And with the entry of sophisticated imaging and advanced molecular techniques, he said that treatment of high-risk disease will be better personalised.
“AS appears safe in well-selected patients, and race alone should not be a contraindication to AS,” Carroll said in his concluding remarks. He also noted that younger men have lower progression rates and that selected patients with GS 3-4 disease are candidates for AS.
Moore, meanwhile, discussed the current use of MRI and the factors that affect the efficiency of MRI in active surveillance. She said among the benefits of MRI is its ability to detect higher-grade disease at first MRI-targeted biopsy, capacity to assess the whole prostate, its non-invasiveness and without infection risk, and it can be combined with other tools such as PSA and risk calculators.
“Three to 9% of higher grade diseases are not detected and artefact can distort some sequence,” said Moore. She also took note of the financial costs of MRI procedures and that MRI does not rule out repeat of standard biopsies particularly in younger patients and those with Gleason scores 3 and 4 at baseline.
Impact of genomics
Falzarano presented an overview on the role of pathology in prostate cancer and AS, and the expected potentials of genomic tests in PCA. She discussed the changes in the Gleason grading scheme and took note of relevant PCA patterns such as the Intraductal Carcinoma of the Prostate (IDC).
“Biomarkers are offering independent prognostic information beyond traditional risk stratification tools to deliver the right care to the right patient at the right time,” said Falzarano as she stressed that the cost-benefits of genomics-driven care must be weigh against that of traditional approaches.
“Changes in pathology practice affect patient risk stratification and active surveillance eligibility,” she said.
Klotz gave a succinct presentation on the issue whether AS is justified in 3+4 cancers (prognostic group grade 2). He said that among the changes in the AS landscape include the nature of occult high-grade disease, flaws of PSA kinetics as trigger and the emergence of mpMRI use, among others.
Giving a summary of what is known regarding staging, Klotz said the molecular genetics of Gleason pattern 3 resemble normal cells and that pattern 4 has many molecular hallmarks of cancer
“The metastatic potential of Gleason 3 is zero. But pathologic miss of co- existent higher grade cancer is the major limitation of current diagnostic strategy,” noted Klotz as he added that although true biological grade progression occurs, it is uncommon.
He also gave a concise view of what he called as the “new grey zone” in active surveillance, saying that compared to previous years this grey zone has somewhat “shrunk.”
“The new grey zone includes extensive Gleason 6, Gleason 6 in men younger than 50 years, Gleason 7 with less than 10%, Gleason 4 or favorable genetic score,” said Klotz as he mentioned that the “black zone” in AS would be Gleason 6 which is non-extensive disease, non-suspicious MRI and a low PSA density.
Klotz gave the following concluding remarks:
- Gleason 3 lacks most hallmarks of cancer;
- Presence of Gleason 4 confers significant increased metastasis risk at 15 years;
- Today’s grey zone includes high-volume Gleason 6 in young patient; and
- Most Gleason 7 should be treated.