Imagine it’s 1995. The PSA blood test has recently been deployed for widespread screening. You’re 73 with a mild heart problem. Your doctor suggests you have a PSA test as part of your annual physical. It comes back at 13.5 ng/mL. After a 6 needle TRUS biopsy (yes, a standard sextant biopsy back then meant 6 needles) your Gleason score comes back: 4+4 = 8. Uh oh. You have prostate cancer PCa. Since you’re 73 and have a heart condition, your doc says you’re not a candidate for surgery. Therefore, you join the roughly 32% of men having 6 weeks of beam radiation.^[i] By late 1996, your PSA has fallen to 1.2 ng/mL—yay!—and it stays there for about 20 months. Then it begins to rise, which continues for the next 8 months. Your doctor says this is called biochemical recurrence, and it means your PCa is back. Again, uh oh. It’s almost 1999 and you’re pushing 78. What do you do now?

Prior to 2000, the American Urological Association (AUA) recognized only one way to perform a potentially curative salvage treatment: surgical removal of the whole gland, or salvage prostatectomy (salvage RP). But there’s a big problem. The aftereffects of radiation have deformed the prostate and the tissue around it with tough scar tissue. This makes salvage RP quite difficult, and side effects are very common. Almost all patients were left with erectile dysfunction, 80% had some degree of urinary incontinence, and rectal injury affected 5-10%.^[ii]

Also, as a rule beam radiation cannot be done as a salvage treatment without risks of complicated side effects and secondary cancers. NOTE: some practitioners will offer salvage brachytherapy (implanting radioactive seeds), but it should not be confused with ablation since cancer death is not immediate.

Introduction of ablation

In the mid-to-late 1990s, image-guided, minimally invasive ablation (tissue destruction) methods were introduced as a primary (first) treatment for PCa. The notion of whole-gland salvage ablation as an alternative to prostatectomy or radiation slowly gained traction. In 2000, the AUA issued a position statement on cryosurgery (freezing, also called cryotherapy, cryoablation, or simply cryo) as a whole gland salvage treatment for localized recurrence. Many urologic surgeons initially scoffed, but the FDA eventually approved whole gland cryo as salvage therapy—the key being that cancer was still contained. Salvage whole-gland cryo had fewer side effects than salvage RP, but it still was hard on peeing and sex.

How about focal salvage ablation?

This led to new logic: if salvage ablation can destroy the whole gland, why not target just the cancerous area as a way to reduce side effects even more, yet still control the recurrent PCa? This idea was met with caution; as a 2012 paper pointed out, radiation recurrence was often on both sides of the gland, and in more than one zone. “It is often high grade, bulky and close to the urethra. These findings suggest that planning salvage focal therapy after radiation failure will be difficult.”^[iii] On the other hand, that same year a team from University College London published 2-year results for 39 radiation recurrent patients who had been treated with focal HIFU. Their treatment strategy had been planned after MRI evaluation and transperineal biopsy to confirm that PCa was still contained, and to pinpoint its exact location. The HIFU results were promising. At 2 years after treatment the PCa progression-free survival was 58%. Though post-HIFU sexual function worsened, at 17 months’ follow-up the pad-free continence rate was 87.2%. Thus, “focal salvage therapy is a potential strategy for localized recurrence after radiotherapy that may reduce the harms resulting from whole-gland salvage therapies.”^[iv]

Coming up to the present, salvage focal ablation for radiation recurrence is now more widely recognized. For instance, a 2016 review of 12 published papers concluded, “Provisional data suggest that [biochemical disease free survival] rates of focal salvage are in line with those of whole-gland approaches.”^[v] In 2018, gains in focal salvage treatments were noted:

To achieve such tumor-targeted treatment, imaging developments have made it possible to better exclude metastatic disease and accurately discriminate the tumor. Currently, focal salvage treatment is being performed with different modalities, including brachytherapy, cryotherapy, high-intensity focused ultrasound (HIFU), and stereotactic body radiation therapy (SBRT). Oncologic outcomes seem comparable to whole-gland salvage series… There is evidence that focal salvage could decrease severe toxicity and preserve erectile function.^[vi]

A 2020 analysis of 15 studies covering either focal cryo, brachytherapy, or HIFU as salvage therapies found that severe side effects were rare, and concluded, “Rates of metastasis were low after all salvage modalities, as were conversion to second-line therapies” and “salvage focal ablation of radiorecurrent prostate cancer provides acceptable oncological outcomes and is well tolerated.”^[vii]

Is salvage focal ablation right for you?

Salvage focal ablation is not right for every case of radiation recurrence. High-risk patients have higher rates of biochemical failure (rising PSA). It’s of utmost importance to consider all risk factors in diagnosing radiation recurrence: PSA and its derivatives, multiparametric MRI with PI-RADS score, Gleason score based on biopsy, and the location plus extent of disease (based on mpMRI and biopsy).

The Sperling Prostate Center offers MRI-guided focal ultrasound ablation as a salvage treatment for radiation recurrent PCa that is contained in the prostate. In addition to the risk factors of PSA and Gleason score, our expert team utilizes the benefits of our 3T multiparametric MRI prostate scan to obtain a high resolution, 3-D portrait of the prostate and any suspicious lesions it contains, while the PI RADS score assesses the risk level, helping us determine if a focal treatment is appropriate for each patient. Research confirms the value of MRI for diagnosis, treatment choice, and treatment planning for cases of radiation recurrence.^[viii]

For more information, contact the Sperling Prostate Center.

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] https://seer.cancer.gov/archive/publications/prostate/prostate_monograph.pdf
[ii] Light A, Peters M, Reddy D, Kanthabalan A et al. External validation of a risk model predicting failure of salvage
focal ablation for prostate cancer. BJU Int. 2023 Nov;132(5):520-530.
[iii] Leibovici D, Chiong E, Pisters LL, Guo CC et al. Pathological characteristics of prostate cancer recurrence after
radiation therapy: implications for focal salvage therapy. J Urol. 2012 Jul;188(1):98-102.
[iv] Ahmed HU, Cathcart P, McCartan N, Kirkham A et al. Focal salvage therapy for localized prostate cancer
recurrence after external beam radiotherapy: a pilot study. Cancer. 2012 Sep 1;118(17):4148-55.
[v] Duijzentkunst DA, Peters M, van der Voort van Zyp JR et al. Focal salvage therapy for local prostate cancer
recurrences after primary radiotherapy: a comprehensive review. World J Urol. 2016 Nov;34(11):1521-1531.
[vi] van Son M, Peters M, Moerland M et al. Focal Salvage Treatment of Radiorecurrent Prostate Cancer: A
Narrative Review of Current Strategies and Future Perspectives. Cancers (Basel). 2018 Dec 3;10(12):480.
[vii] Khoo CC, Miah S, Connor MJ, Tam J, Winkler M, Ahmed HU, Shah TT. A systematic review of salvage focal
therapies for localised non-metastatic radiorecurrent prostate cancer. Transl Androl Urol. 2020 Jun;9(3):1535-
1545.
[viii] van der Poel H, Grivas N, van Leeuwen P, Heijmink S, Schoots I. The role of MRI for detection and staging of
radio- and focal therapy-recurrent prostate cancer. World J Urol. 2019 Aug;37(8):1485-1490.