Indolent cancers: The fine art of sophisticated pathology

Identifying patients with indolent cancers from those with aggressive disease are one of the many challenges faced by many doctors. Thus, the least visible specialist such as a pathologist could actually be holding the crucial key in diagnostic and treatment processes.

The upcoming 8th European Multidisciplinary Meeting on Urological Cancers (EMUC16) to be held in Milan (IT) from 24 to 27 November reflects the central role of pathologists with the three-day event preceded by the 2016 EMUC Symposium on Genitourinary Pathology which aims to provide the latest updates in genitourinary pathology.

Prof. Jonathan Epstein, the Reinhard Professor of Urologic Pathology at Johns Hopkins Medical Institutions and Director of Surgical Pathology Department of Pathology, Johns Hopkins Hospital, is an opinion leader in his field and is known for his body of work on precursors of prostate cancer, grading prostate cancer, the diagnosis of limited adenocarcinoma on needle biopsy and predicting progression following radical prostatectomy. Epstein would open the half-day symposium with his lecture “Latest novelties on the WHO morphological classifications of genitourinary cancers.”

“The last edition of the WHO Classification of Tumours of the Urinary System and Make Genital Organ was in 2004. Since that publication, there have been numerous changes in the field of urological pathology which have been updated in the new 2016 WHO morphological classification of genitourinary cancers,” said Epstein.

New knowledge and classifications have been developed in the pathology and genetics of these tumours. One of these is intraductal carcinoma of the prostate, a newly recognized entity which is included in the 2016 WHO classification. In many cases this carcinoma involves intraductal spread of aggressive prostatic carcinoma and should be separated from high-grade prostatic intraepithelial neoplasia (PIN). Epstein is known for his extensive work in high-grade PIN and intraductal carcinoma. At the EMUC he will also elaborate on the impact or significance of a new grading system for prostate cancer that is more patient-centric which is easier to understand and more in line with prognosis.

“Urological tumors are becoming more precisely classified based on a combination of morphology, immunohistochemistry, and molecular findings. Treatment protocols can therefore be tailored more precisely to the specific subtype of the tumor,” said Epstein as he noted that the goal is not only for the doctor to determine proper treatment, but also – and equally important- to avoid unnecessary intervention.

“At the other end of the spectrum, there is growing recognition that some urological cancers do not need aggressive therapy and can be followed carefully with active surveillance,” according to Epstein. “The terminology of some of these tumors in different GU organ systems has been changed to better reflect their more indolent behavior to, hopefully, help in preventing overtreatment.”

New molecular tests

Unfortunately, diagnosing prostate cancer and the pathology work involved in examining diseased cells is complex and even two pathologists looking at the same biopsy tissue may come up with conflicting opinions. Aside from expertise and experience, new technologies, however, can make a difference and can help both the pathologist and clinician.

“Newer molecular tests will be combined with morphology and immunohistochemistry to further our classification and improve prognostication of various GU malignancies. It has already been shown the combination of both molecular and more standard tests are better than either of them by themselves,” said Epstein.

He also said that with modern approaches and technology-centered diagnostics, it is essential that hospitals maximise the role of multidisciplinary teams.

“Every institution should have a routine multi-disciplinary GU Oncology conference attended by urologists, medical oncologists, radiation oncologists, radiologists, and pathologists to go over unusual and problematic cases to insure the best possible treatment for these patients. Follow-up on the same cases should also be presented so that everyone can learn on the success of the conference recommendations,” he added.

Not only a medical scientist, Epstein as an educator highlights the importance of knowledge and skills-sharing.

“Meetings like the EMUS are one of the best ways to disseminate the latest information about GU malignancies to a multi-disciplinary audience. In contrast to publications, these meetings allow back and forth dialogue between the disciplines,” he said. “For example, as it relates to my discipline, it allows GU oncologists to ask questions to a urological pathology expert and for me to hear about how our diagnoses affect therapy and what additional pathological issues need clarification.”

Future developments

Asked what he expects to be major developments in the coming years, Epstein said he sees a more expanded role of so-called ‘personalised treatment.’

Epstein: “Therapies in 10 years from now will be more “personalised” to specific genetic abnormalities within the patient’s own specific tumor. However, these molecular findings will still need to be taken in the context of routine morphology and special testing done by pathologists which will also evolve over the next decade. In 10 years, there will also be additional tests to better identify those indolent tumors that may be more safely followed.”

He mentioned that by far the most numerous changes in the classification of GU malignancies have been in renal cell carcinoma. “In the not too distant past, tumors were classified descriptively as ‘clear cell, ‘papillary’ and ‘eosinophilic.’ Currently, these general non-specific terms have been replaced by a more precise classification based on a combination of clinical, cytogenetics, immunohistochemistry, and molecular findings.

Nonetheless, there is still a greater percentage of renal cell carcinomas that currently remain unclassified compared to any other GU organ.”

In the next decade, according to Epstein, it is likely that this unclassified category in renal cancer will shrink as new entities are discovered.

“The correct diagnosis of these new subtypes of renal cell carcinoma, some of which can only be done in select centers, is not that critical since for most of them the treatment does not differ. Hopefully, this will change in the future with more targeted therapies,” said Epstein.

The EMUC symposium programme will also feature a lecture on the 8th edition of the TNM staging (AJCC and UICC) of the genitourinary tumors with M. B. Amin (USA) focusing on the implications from January 2017 and beyond. The lecture will be followed by a round table forum on the topic “From morphology to personalised medicine in genitourinary cancers.”

For other details on EMUC 16 and the 2016 EMUC Symposium on Genitourinary Pathology, click on this link: http://emuc16.org/