The Return of Metastatic Prostate Cancer

Henry Rosevear, MD


October 07, 2021

Like all great villains, left to its own devices, prostate cancer will do exactly what prostate cancer does: take over. Given the generation of doctors for whom a patient presenting with metastatic prostate cancer used to be a true medical zebra, it's time to educate everyone on the condition's evolving incidence.

Let's go back 40 years to the early 1980s — the days of the Walkman, big hair, and Pac-Man. According to SEER data at that time, the incidence of prostate cancer was about 100 per 100,000 men, as it had been since 1975 when data collection began. In the mid-1980s, the incidence started to rise and eventually peaked in 1992 at 237 per 100,000 before leveling off in the high 100s for the next 20 years.

In 2012, the incidence precipitously dropped back to the low 100s. Why the variation?

The rise and fall of prostate cancer rates largely parallel the use of population screening with prostate-specific antigen (PSA) testing. As PSA testing became more common in the mid-1990s and 2000s, the incidence of prostate cancer rose. Then in 2012, when the US Preventive Services Task Force recommended against the use of population-based PSA screening, the incidence went down. If you don't look for a disease that is asymptomatic for a long period of time, you won't find it.

And no, this is not an article about the pros and cons of population-based PSA screening. Two large randomized studies, which explored the utility of PSA screening combined with aggressive intervention of all newly diagnosed cases, have been reviewed at length, showing at best marginal survival benefit using such a screening and treatment algorithm.

Alternatively, we could look at the variation in the prevalence of metastatic prostate cancer but that is complicated by the evolution in treatment options. Just over the past 10 years, the treatment of metastatic prostate cancer has been revolutionized by the introduction of numerous second-generation hormone therapies, immune therapies, and most recently the introduction of PARP inhibitors. These treatments are keeping patients alive longer and hence increasing the prevalence, though not the incidence, of the disease.

Rather, this article explores one of the consequences of fluctuations in prostate cancer screening with PSA — namely, the change in incidence of metastatic prostate cancer.

We have already discussed how the incidence of prostate cancer changed over the past few decades, but how has the incidence of metastatic prostate cancer changed? According to a 2020 study, the incidence of metastatic disease at diagnosis went from 4% to 8% between 2003 and 2017. These data were supported by another study presented at this year's Genitourinary Cancers Symposium that showed a similar rise.

And that shouldn't be surprising. When you look back at the SEER data from the 1980s, the incidence of metastatic prostate cancer was 12%. That number decreased between 1990 and 1994 to 10% and then to 5.5% between 1995 and 1999, before leveling off at 4% by 2000. That trend follows the rise in incidence of prostate cancer in general as PSA screening was introduced.

It is clear that PSA screening identifies patients with prostate cancer and led to a stage migration for the disease. Once the use of PSA screening decreased, the incidence of prostate cancer, in general, went down. But that decrease in PSA screening, in turn, led to an increase in the incidence of metastatic disease at diagnosis. If we assume that the underlying disease has not changed over the past 40 years, we may see the incidence of metastatic prostate cancer return to where it was before PSA screening: 12%.

Given the significant increase in incidence, metastatic prostate cancer needs to be considered part of the differential diagnosis for any patient who presents with relevant signs or symptoms, including bone pain, pathologic fractures, urinary retention, unexplained weight loss, and renal failure.


While PSA is an appropriately controversial test for population-based screening, as a diagnostic tool for the evaluation of potential metastatic prostate cancer, it has been very good. Further, the numerous advances in the treatment of metastatic prostate cancer have dramatically improved the life expectancy of these patients once they have been properly diagnosed, only highlighting the need for early diagnosis.

The challenge going forward will be identifying patients with earlier-stage prostate cancer who need intervention and then treating them in a manner that maximizes both quality and quantity of life. Until we solve that problem, everyone will need to become more comfortable with diagnosing and treating more men with metastatic prostate cancer.

Henry Rosevear, MD, is a private-practice urologist based in Colorado Springs, Colorado. He comes from a long line of doctors, but before entering medicine he served in the US Navy as an officer onboard the USS Pittsburgh, a fast-attack submarine based out of New London, Connecticut. During his time in the Navy, he served in two deployments to the Persian Gulf, including combat experience as part of Operation Iraqi Freedom.

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