<p>Improvements in imaging technology allow for the detection of locally recurrent prostate cancer, even in patients with low prostate-specific antigen (PSA) levels. There are numerous options for salvage therapy, including cryotherapy, radiation therapy, surgery, and high-intensity–focused ultrasound, but when and in whom to use these therapies are still being debated.</p>

Focal therapy, as it might be applied to salvage therapy, is controversial because there are very little data to support its benefit in that setting. At my center at Duke, salvage cryotherapy is very popular, but it is primarily a whole-gland treatment. If a patient develops a biopsy-proven recurrence after external beam radiation therapy or brachytherapy, they will freeze his entire prostate but will not commonly do focal therapy in that setting.

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For patients with a high-risk recurrence and a PSA level above the recurrence threshold, the addition of 4 to 6 months of hormone therapy to salvage radiation therapy is beneficial. On a practical level, I also recommend hormone therapy, along with salvage radiation therapy, in patients who may have been lost to follow-up or were not being followed closely but then present with a PSA of greater than 1.5 ng/mL in a recurrent setting. At that point, these individuals are past the ideal point for salvage radiation therapy. That is where the studies seem to really show the biggest benefit of hormone therapy due to the likely presence of micrometastatic disease.

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I am not a big fan of salvage radical prostatectomy because of the high associated morbidity, so I have done relatively few. For example, after salvage surgery, patients tend to have incontinence that lasts a long time, and almost all patients have impotence. There is also a risk of sustaining rectal injury and, in rare cases, needing a temporary colostomy. In my experience, when you counsel patients about salvage radical prostatectomy, a lot of them run for the door. However, for the carefully selected younger men with a high probability of localized disease, robotic experts are touting success.

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One area of concern that I really want readers to be aware of is the PSA cutoff that the American Urological Association/American Society for Radiation Oncology/Society of Urologic Oncology (AUA/ASTRO/SUO) guidelines use in their recommendations for salvage therapy after radical prostatectomy. Currently, these guidelines recommend that, for patients with a PSA level of 0.2 ng/mL or greater after radical prostatectomy, you should consider salvage radiation therapy, as salvage radiation is more effective when given to patients with lower levels of PSA. That is all well and good, except benign residual prostate tissue can also produce PSA. A very large study using a radical prostatectomy registry found that some patients with detectable PSA did not develop a cancer recurrence, and the authors were strongly in favor of using a PSA cutoff of 0.4 ng/mL or greater.

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The AUA/ASTRO/SUO guidelines also say that early salvage radiation therapy, especially when PSA levels are at or even below 0.2 ng/mL, can significantly improve biochemical disease-free survival in patients who are at high risk of disease progression. These series of early salvage radiation are impacted by a certain percentage of men who just have a benign PSA rise. If a patient has a negative prostate-specific membrane antigen positron emission tomography, does not have very high-risk surgical pathology risk factors, and has a PSA level of less than 0.5 ng/mL, I hold off on doing salvage radiation therapy right away. That is different from the expert opinion provided in the guidelines, which is that salvage radiation therapy should not be withheld if there is a negative positron emission tomography. I personally do not agree with this because the guidelines do not take into account data from the Mayo Clinic Registry and others stating that PSA levels of up to 0.4 ng/mL are not always cancer related.