When you think of turning points in history, what comes to mind? The fall of the Berlin Wall? Einstein’s theory of relativity? The women suffragettes? Toppled regimes, scientific discoveries, and allowing women to vote dramatically alter the course of human events. Sometimes, however, the wheel of change is not obvious. You might be in the midst of a revolution and not even know it.

This is the case when it comes to managing prostate cancer (PCa). For 25 years we’ve been transitioning away from the all-or-nothing PCa strategies. While we don’t know how this transition will finally end up, at the moment there are two middle ground strategies for men diagnosed with low risk PCa:

• Active Surveillance (AS) leaves the cancer untreated while monitoring for disease progression. Typically, monitoring involves a combination of PSA, MRI and biopsy at mandated intervals. This allows a patient to hold off on having a whole-gland intervention (surgery, radiation, or ablation). Patients are also recommended to actively embrace dietary and exercise habits shown to reduce PCa risk (anti-inflammatory diet, aerobic exercise, stress management, etc.). Monitoring results may trigger a move to definitive treatment.
• Focal therapy applies a minimally invasive intervention (ablation using intense heat or cold) to destroy the index lesion plus a pre-emptive margin of safety, while sparing healthy prostate tissue. Treatment success is monitored by scheduled PSA testing and MRI. Test results may trigger biopsy for suspected recurrence.

A study of thorough AS monitoring finds it safe

A 2024 published paper reports long-term outcomes of patients on AS who adhered to their clinical study monitoring protocol.^[i] The study was called The Canary Prostate Active Surveillance Study (PASS) and it began in 2008. Ultimately, 2155 men enrolled, all of whom had favorable-risk PCa and no prior treatment. They were tracked until Aug. 2022 (average follow-up 7.2 years). The authors note that “… 10 years after diagnosis, 49% of men remained free of progression or treatment, less than 2% developed metastatic disease, and less than 1% died of their disease. Later progression and treatment during surveillance were not associated with worse outcomes.” It found that AS is an effective strategy as an alternative to immediate whole gland intervention—in other words, a safe middle ground.

Achieving these results was a product of a more thorough monitoring protocol than usual. It was designed to adequately biopsy the prostate to reduce the chance of missing any high-risk tumor cells, and to capture disease progression at the earliest possible time. From the patients’ viewpoint, prompt diagnosis of any uptick in PCa activity meant prompt treatment for best success odds. Here is the protocol:

• From time of entry, PSA tests were done every 3 months before 2020, then every 6 months from 2020 onward.
• Physical exams (including digital rectal exams followed by urinalysis) were done at time of entry and then every 6 months throughout the study.
• Patients diagnosed within a year of enrollment have a repeat biopsy at their baseline study visit (if previous biopsy did not have at least 10 cores). Then a repeat biopsy at 6-12 months from baseline visit; then at 2 years, followed by biopsy every 2 years throughout the study.
• Patients diagnosed more than a year prior to entry would have a baseline biopsy at time of entry if only 1 prior biopsy was done, or if the most recent biopsy was over 2 years prior to entry, then every 2 years from the most recent biopsy.

If this protocol seems like a burdensome demand on participants, it’s no surprise. Showing up for appointments at least every 6 months requires true commitment, but the thorough requirements greatly benefit science. A noteworthy feature of this study is the collection and storing of biomarkers (tissue, blood, urine). In fact, it contributed a repository “… to discover and/or confirm biomarkers that are predictive of progressive and/or aggressive prostate cancer, with an emphasis on confirmation.”^[ii] This amounts to a treasure trove of information not only for PASS but also for future research.

Now, not all protocols in the world of PCa Active Surveillance are as stringent as the PASS study, and therefore not as safe. A news write-up tells us, “The high level of biopsy adherence may contribute to lower rates of metastasis than reported in other studies, the investigators noted. Canary-PASS mandated a prostate biopsy even with stable serum PSA and normal multiparametric MRI results.”^[iii] This is another way of saying, less rigorous AS monitoring protocols risk missing PCa progression and therefore missing a potentially curative treatment window. In addition, many men on AS through their doctors (that is, not on a clinical trial) often skip repeat biopsies. They may or may not realize they are putting themselves in danger, but fear and anxiety are powerful drivers. Or, they decide to go off AS and get surgery or radiation because they find it too nerve-racking to think of PCa growing in their body.

Something to consider

Here’s something to think about: Focal therapy is another middle ground besides AS. It offers the benefits of both intervention AND monitoring in order to hold off on a whole gland treatment.

• ✓ The index tumor is ablated by a method such as Focal Laser Ablation, TULSA, or Exablate. This eliminates worry about cancer progression.
• ✓ Following treatment, a reasonable monitoring protocol is put into place. It combines PSA and MRI in order to confirm effectiveness within the zone of ablation, and to check for any new PCa in the untreated portion of the gland.
• ✓ Unlike whole-gland treatments, focal therapy has a very high rate of successfully preserving sexual and urinary function.

We can’t yet foresee a history-making PCa breakthrough, but for now, focal therapy offers peace of mind and high quality of life without the heavy work of a highly safe AS protocol like PASS.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Newcomb LF, Schenk JM, Zheng Y, Liu M et al. Long-Term Outcomes in Patients Using Protocol-Directed Active Surveillance for Prostate Cancer. JAMA. 2024 May 30:e246695. doi: 10.1001/jama.2024.6695.
[ii] Newcomb LF, Brooks JD, Carroll PR, Feng Z et al. Canary Prostate Active Surveillance Study: design of a multi-institutional active surveillance cohort and biorepository. Urology. 2010 Feb;75(2):407-13.
[iii] Persaud, Natasha. “Safety of Protocol-Directed Active Surveillance Confirmed.” Renal&Urology News, June 11, 2024. https://www.renalandurologynews.com/news/safety-of-protocol-directed-prostate-cancer-active-surveillance-confirmed/.