Non-metastatic castration-sensitive prostate cancer, or nmCSPC, is a type of prostate cancer…

…That includes newly diagnosed localized or regional disease, as well as biochemical recurrence, or BCR. It is important for us to 

understand the possible prognosis of nmCSPC patients with high-risk biochemically recurrent disease. 

PSA doubling time, or PSADT, is correlated with outcomes such as progression to metastases and death. 

A rapid PSA doubling time…

…Specifically less than or equal to 9 to 12 months, in patients with localized disease who have received definitive therapy has been shown 

to indicate high-risk BCR likely to progress to metastatic disease and poor survival.

In a retrospective cohort study, data from 1997 men undergoing radical prostatectomy were analyzed. 

Of these, 304 men developed biochemical PSA elevation….

…Of which 34% progressed to metastatic disease.

The Kaplan-Meier curve here shows that patients with a PSA doubling time of less than 10 months were more likely to experience metastasis than those with a slower PSA doubling time. At 10 years following PSA recurrence, the majority of patients with a PSA doubling time of less than 10 months had progressed to metastatic disease. 

Because this was a retrospective study, the data is subject to limitations, as noted here. In addition, the size of the group analyzed for PSADT was relatively small. So, results should be considered preliminary

Taking this into consideration, and coupling it with the results shown here, monitoring our patients’ PSA levels closely is very important in understanding the risk of progression. 

More information on this study can be found at psadoubling.com. 

Another retrospective study explored risk factors for prostate cancer-specific mortality. 

Data from 379 men with nmCSPC post radical prostatectomy… 

…stratified by PSA doubling time, were analyzed.

When looking at the prostate cancer-specific survival curves, shown here, we can see a drop in survival for patients with high-risk BCR.

Within 10 years, more than half of all patients with a PSA doubling time of 3 to 9 months…

...and the majority of patients with a PSA doubling time of less than 3 months, had died. 

The limitations of this retrospective cohort study include data quality factors and loss of patients to follow-up. Because this study was nonrandomized, results are subjected to potential confounding by unmeasured variables and sampling biases. 

Other key limitations include small subgroup size and large confidence intervals; a predominantly white population; and calculation of PSA doubling time based on the assumption that PSA levels increase. 

External validation from other, similar studies, or from prospective clinical trials is necessary.

More information on this study can be found at psadoubling.com. 

In summary, we’ve seen evidence that nmCSPC patients with a rapid PSA doubling time of less than or equal to 9 to 12 months represent an 

important subset of patients who are at increased risk of poor outcomes. 

It’s important that we understand PSA doubling time as that can be a sign of a heightened risk for the development of symptomatic metastatic disease.

Approximately one-third of men with prostate cancer may experience biochemical recurrence within 10 years after receiving definitive therapy.

Even further, following initial PSA elevation after prostatectomy, the median time to progress to metastasis is 8 years.

Monitoring PSA levels and PSA doubling time is an important factor in the risk of disease progression. 

Some patients with biochemically recurrent non-metastatic castrate sensitive prostate cancer… 

…May exhibit such a rapid PSA doubling time that indicates a high risk of future progression to metastatic disease and poor survival.

Let’s take a look at two hypothetical patients.

Gregory is a 58-year-old architect who was diagnosed with prostate cancer 2 years ago, with a Gleason score of 8. 

He's previously been treated with prostatectomy and salvage radiotherapy but began to see an increase in PSA less than a year later.

His PSA level is currently 2.5, with a PSA doubling time of 2.8 months. 

Nicolas, a 61-year-old pharmacist, had a similar history. 

Diagnosed with prostate cancer in November 2020, Gleason score of 6, he also received prostatectomy and salvage radiotherapy.

However, within 8 months following treatment, his PSA began to rise. His current PSA level is at 9, with a PSA doubling time of 5 months.

If we compare Gregory and Nicolas's stories, we see some interesting trends. Looking at their PSA levels, we see that Gregory's current PSA level is lower than Nicolas's. 

But regardless of the extent of PSA level elevation, if a patient with biochemical recurrence has a PSA doubling time of 9 to 12 

months or less, he is considered at high risk of disease progression. 

So, despite Gregory's PSA level being lower than Nicolas's, based on their PSA doubling times, both of these patients are at high risk of 

developing metastatic disease.

Let's take a look at one last hypothetical patient.

Hector is a 68-year-old man who was diagnosed with prostate cancer 4 years ago. At diagnosis, he had a Gleason score of 7. Hector received radiation therapy as his definitive treatment, but 2 years later his PSA began slowly rising. 

His current PSA is 2.8, with a doubling time of about 11 months.

Though his PSA is not rising as quickly as other patients, his PSA doubling time still falls within 9 to 12 months or less, indicating that he is also at high risk of poor outcomes. 

In summary, as we've seen with Gregory, Nicolas, and Hector, monitoring a patient's PSA doubling time is important. 

regardless of the extent of PSA level elevation, PSA doubling time can help to determine if a patient with biochemically recurrent non-metastatic castrate sensitive prostate cancer may be at high risk of disease progression. 

PSA doubling time of 9 to 12 months or less could indicate a risk of poor clinical outcomes including metastatic disease and mortality

For patients who have received definitive therapy, detectable or rising prostate-specific antigen, or PSA levels, can often be associated with the first sign of recurrent disease. 

Because biochemical recurrence is often asymptomatic, PSA surveillance is important.

Trends within treatment guidelines and clinical data indicate that high-risk biochemical recurrence, or high-risk BCR, can be understood 

as rapid PSA doubling time, otherwise known as PSADT. 

Both the American Urological Association (or AUA) and the National Comprehensive Cancer Network (or NCCN) provide guidance on monitoring PSA levels after definitive therapy. While the guidelines discuss evidence that rapid PSA doubling time, or PSADT, is correlated with a risk of progression… 

… they do not have a definition of “high-risk BCR”

Several studies have shown the impact of short doubling times and their association with poor clinical outcomes, such as the risk of metastasis and mortality—in this patient population.

Because of this, we refer to high-risk BCR as a range—having a PSA doubling time of less than or equal to 9 to 12 months

Let’s take a closer look at the various treatment guidelines. 

The AUA recommends that PSA levels should be monitored every 3-6 months for the first two years after a patient receives local treatment. 

Subsequent monitoring between years 2 and 5 should occur every 6 months, with monitoring annually thereafter. 

NCCN recommendations are a little bit different. Here, patients should be monitored every 6 to 12 months for 5 years after initial definitive therapy, and then annually. For high-risk patients, PSA should be measured every 3 months. 

In summary, discrepancies in defining high-risk BCR and the frequency in monitoring indicate the need for further education around PSA doubling time. It is critical to understand high-risk BCR and the correlation of PSA doubling time with risk of potential disease progression.