Zachary Klaassen: Hello, and thank you for joining us for this NCCN Clinical Practice Guideline in Oncology Prostate Cancer discussion. Today, we'll be discussing the epidemiology, initial diagnosis, and life expectancy with prostate cancer. My name is Zachary Klaassen. I'm an Assistant Professor at the Division of Urology at the Medical College of Georgia. And with me today is Christopher Wallis, an Assistant Professor in the Division of Urology at the University of Toronto.

In this session, in this talk today, we'll be discussing an overview of prostate cancer epidemiology, as well as the initial prostate cancer diagnosis, and the importance of estimating life expectancy in these patients when we see them in our clinic.

Starting with epidemiology, most viewers will know that there's an estimated 191,000 new cases of prostate cancer that will be diagnosed each year in the United States, which accounts for roughly 21% of new cancer diagnoses in men.

The age adjusted death rate from prostate cancer has declined by 52% from 1993 to 2017. Over of some concern is that the death rate has been stable over recent years, which we'll discuss further. It Is estimated that prostate cancer will account for 10.4% of male cancer deaths per year in the United States, which is roughly 33,330 deaths.

Moving on to the US Preventative Task Force and their role over the last decade in diagnosis. Certainly early detection can lead to overtreatment of prostate cancer that do not threaten life expectancy and this results in unnecessary side effects that impair quality of life, as well as increasing healthcare expenditures. So at this point in 2012, the US Preventative Services Task Force recommended against PSA testing, which was a landmark blow to the field of urology. And by reviewing the evidence, the USPSTF looked at the benefit and harm of PSA-based screening for prostate cancer.

They also reviewed the benefits and harms of treatment of localized prostate cancer and returned a Grade D recommendation, recommending against a PSA-based screening, which applied to all men in the population regardless of age. Because of this, the incidence of metastatic disease has increased over the last several years. Cancer mortality, which I mentioned previously had decreased in the previous decades, but is subsequently stabilized. And there's recent evidence that prostate cancer deaths have also increased from 26,730 in 2017 to 31,620 in 2019. This increase in the incidence of metastasis of presentation of prostate cancer death may be influenced by declines in the rates of prostate cancer, early detection, biopsy, and treatment with radical prostatectomy.

So from 2012 to 2018, the USPSTF did upgrade their screening recommendations, as I've listed here with this screenshot. And this particularly implies men age 55 to 69 now have a Grade C recommendation, which is suggested that these men undergo PSA screening and a shared decision-making with their physician, essentially weighing the risks and benefits of PSA screening and subsequent potential treatment. As you see here, this still is a Grade D recommendation for men over the age of 70 years, with regards to PSA and prostate cancer screening.

I'll now turn it over to Chris who will discuss initial prostate cancer diagnosis, as well as life expectancy in the field of prostate cancer.

Christopher Wallis: Thanks Zach. So as we move forward in the NCCN guidelines, we're going to discuss first prostate cancer diagnosis, and most will know that the initial suspicion of prostate cancer is typically based on evidence of abnormality and digital rectal examination or an elevated PSA test performed either for screening or other purposes. However, definitive diagnosis requires a tissue sampling, which is performed most often via needle biopsy under transrectal ultrasound guidance. However, more recently the use to a transperineal biopsy is increasing.

Gleason scores are assigned based on primary and secondary grades at the pathologic evaluation of the biopsy specimen. Further clinical staging in prostate cancers based on the TNM classification. And the recommendations from the NCCN are similarly based on the TNM staging rather than AGCC prognostic groups.

Here, we highlight the TNM staging of prostate cancer. Most people already know this, but dividing first, the primary tumor staging. We have T1 disease, which is clinically inapparent and may be further subdivided on the basis of diagnosis. T2 disease, where the tumor is palpable, but confined within the prostate. And again, subdivided based on the extent of disease. T3 with extra prostatic tumor that does not invade adjacent structures and again sub divided based on the extent of extra prostatic involvement. And T4 disease, where the tumor is fixed or invades adjacent structures, including the external sphincter, rectum, bladder, or pelvic wall.

In terms of pathologic staging of the primary tumor, we have T2 disease organ confined, T3 extraprostatic extension, and T4 similarly invading adjacent structures. Examining lymph nodes, the TNM staging simply divides into N0 for no evidence of nodal involvement and N1 with the regional lymph node involvement. Metastasis is divided into M0 with no evidence of metastatic disease, M1 showing evidence of distant metastases, which is then subdivided into M1a for nonregional lymph nodes, M1b for bony disease, and M1c for other sites of disease, typically visceral.

The NCCN guideline panel emphasizes that synoptic pathology reports are useful, and these may provide clinically useful and relevant information to clinicians and help to standardize reporting. And the College of American pathologists provides a format for providing such synoptic pathology reports.

When we consider treatment approaches and also the question of whether to screen for prostate cancer, estimates of patient life expectancy greatly influence our decision making. And so these may be particularly relevant when we consider the questions of active surveillance or observation versus primarily curative treatments. And so while life expectancy can be relatively easily estimated for large groups, it is somewhat difficult oftentimes to extrapolate these estimates to the individual patient. There are a variety of options for calculating life expectancy, which the NCCN panel highlights and we've listed here. I want to highlight, for example, the Social Security Administration example. And so we can see with increasing age and subdivided by race and gender, the proportion of individuals expected to live to any given age.

The World Health Organization has similar tables. These are helpful because they provide a conditional probability, both the life expectancy at birth, and then conditional on surviving to age 60. And so studying a case example as the NCCN guideline panel has done, we can apply the Social Security Administration life expectancy and examine the effect of co-morbidity among the average 65 year old, the life expectancy is 17.7 years. However, for those who are in the upper quartile of health, life expectancy is 26 and a half years at the same age and for individual in the lower quartile of health, life expectancy may be less than nine years. Thus treatment recommendations could dramatically change in the context of the NCCN guidelines on the basis of judged health, even for a patient of the same age.

And so when we summarize this section of the NCCN guidelines, it's important to remember that prostate cancer accounts for more than one-fifth of all cancer diagnoses among men and 10% of all deaths among men. Initial prostate cancer diagnosis relies on clinical suspicion based on abnormal, but direct examination or elevated PSA and confirmation with a prostate biopsy. When we discuss and consider treatment recommendations, it's important to take into account the patient's life expectancy and encompassing both age and overall health status with a number of tools available to guide us in this risk assessment.

At this point, I'd like to thank you for your time and attention and hope this synopsis of the NCCN clinical practice guidelines has been useful to you. Thanks again.