As I have highlighted in other posts, prostate cancer is heterogeneous and often lethal with more than 30,000 deaths per year. Whether surgery, radiation, cryosurgery, chemo or hormonal ablation therapy, treatment for cancer is challenging, and it takes patience and support, from healthcare providers and family, for patients to get through treatment. Fortunately, patients and their families can be confident that they will be cured once treatment is complete. However, this isn’t always the case, and it can be a great shock to learn that cancer has returned. For the purpose of this blog, I will highlight options that patients may have after getting treated with radiation. I will give a synopsis of real cases where these treatments have been used.
Recurrence after prostate cancer treatment revolves around PSA blood testing. As a tumor marker, there is no better indication for cancer recurrence that PSA testing (this is in contradiction to the use of PSA as a screening test, which as we have pointed out in earlier blogs, has clear limitations. But when cancer has been established the use of PSA testing is critical).
With regards to radiation treatment or any other treatment in which the prostate remains in situ (within the patient), it is more difficult to interpret this test. First, we know that it can take months to years for the PSA to reach a nadir (its lowest point) after radiation. In fact, the longer it takes for the PSA to reduce after radiotherapy, the better the prognosis, and conversely the quicker the PSA falls after radiation the worse the prognosis. This is counter-intuitive, but in general a slow death after radiation results in better cure rates, with best results if PSA levels reach their lowest point after 2 years of treatment).
The most common definition used for a PSA recurrence is the PSA nadir + 2 consecutive rises in the PSA to follow. This should prompt clinicians to actively pursue imaging with CT, Bone Scan and possibly an MRI of the Prostate to evaluate for recurrent cancers. The likelihood of widespread metastatic disease with low PSA number (less than 10) is low. Also, many times the MRI will not pick up localized cancer recurrences. As a result, it is mandatory to proceed with a repeat prostate biopsy to asses for cancer recurrence, especially if no obvious cancer is seen on imaging. In addition, it is critical to biopsy the adjacent seminal vesicles as part of my diagnostic workup (as illustrated by a case below). There are other specialized PET scans (Auxumin, Choline) that are not widely available that can be considered, but there are drawbacks (high rate of false positives) to these tests as well.
Once it’s is confirmed that there is a recurrence of cancer, there are a few options for patients:

1. Radical prostatectomy
The decision to proceed to radical prostatectomy or surgical removal after radiation therapy can be a difficult one. In my experience, most of these patient’s really don’t want surgery and the risks associated with it, particularly urinary incontinence. These man didn’t want surgery upon their initial diagnosis, and usually don’t want to proceed with a riskier surgery with a much higher complication rate later either . Further, these patients tend to be older and have accrued more medical problems as compared to the time of their initial diagnoses.
However, despite drawbacks, it still remains a curative option for many patients, and in experienced surgical hands, can have acceptable outcomes for urinary control (impotence is universal however).

Case example:

65 year old gentlemen who I saw for prostate cancer 7 years ago for low risk cancer. His Gleason score was 6 and his PSA less than 10. He underwent radiation at that time, but had progressive rise of his PSA to over 4 again. Biopsy confirmed recurrent GL 10 prostate cancer in every specimen, and locally advanced cancer without overt metastatic spread to other sites. He underwent surgery to remove his prostate and adjacent lymph nodes. He has incontinence, wearing 3 pads per day. He is 1 year post surgery and has a PSA that is less than 0.2, but is still considered at risk for a future recurrence.

2. Cryosurgery
I have found cryosurgery to be a very attractive option and have cured many patients over the years after radiation failure. It does require general anesthesia, but is a 2 hour outpatient procedure with much fewer side effects than surgical removal. Incontinence is mostly preserved (some patients do have persistent stress incontinence, but generally much less than would have been the case with radical surgery). Essentially, I use small probes placed percutaneously symmetrically throughout the prostate. We use Argon gas to freeze the prostate to -40 degress celcius, and then use Helium gas to thaw out the tissue. Two freeze-thaw cycles are employed to maximize cell/tissue death. We are careful to monitor areas that could create greater complications such as tissues planes near the rectum and the urethral rhabdo-sphincter (muscles recruited during Kegel exercises, to preserve continence). We place a warming device into the urethra which protects it from freezing and injury. Most of these patient’s already have impotence, but if not, cryosurgery results in erectile dysfunction.

Case example:

71 year old patient who underwent combined radiation seeds and external radiation for GL 8 and 9 prostate cancer. His PSA declined rapidly but within 18 months had climbed to over 2. He did not have any recurrence outside of the prostate, but cancer only within the prostate gland. He underwent cryosurgery with me shortly thereafter, and his PSA returned to zero 2 months after surgery. He has nocturia and mild stress incontinence requiring 1 pad per day, but his PSA has remained 0 nearly 12 years after his cryosurgery.

3. Hormonal Ablation therapy
For well over 70 years, it has been established that prostate cells/tissue are sensitive to androgens produced in the body. There are times when patients choose hormonal ablation therapy (i.e., chemical castration) to treat there localized recurrence. The mainstay of treatment is GnRH (gonadotropin releasing hormone) agonists and antagonists delivered via subcutaneous and intramuscular injection. , which blunt the signal from the brain to the testes resulting in the cessation of testosterone production. Surgical castration via bilateral simple orchiectomy is an option, but is permanent and used rarely. Oral antiandrogens can be uses in addition to GnRH agonists to augment therapy by blocking the testosterone receptor on tissues, (testosterone is also produced by the adrenal glands, which is unaffected by blunting hormonal signaling describes above. These oral androgens block the effect of adrenal testosterone).

Case example:

64 year old gentlemen who was treated with radiation therapy 6 years ago. Four years after treatment his PSA increased from less than 1 to over 4 in 6 months. CT and Bone Scan were negative. MRI of the prostate was negative as well for recurrent cancer. He underwent a prostate biopsy and was found to have Gleason 7 and 8 prostate cancer throughout his prostate, and within the seminal vesicles as well. He was counseled to proceed with radical prostatectomy, but as he continued to work construction, was very concerned about incontinence. He was not a candidate for cryosurgery as the cancer was already beyond the capsule of the prostate into the adjacent seminal vesicles. He chose to proceed with hormonal ablation therapy and was started on GnRH antagonist, leuprolide acetate. Despite achieving Testosterone levels less than 20 (castrate levels), his PSA did not decrease below 2 while on these monthly hormonal shots. He was started on a daily pill, Bicalutamide, an oral anti-androgen, and his PSA quickly became undetectable. His PSA remains undetectable now nearly 18 months into combined treatment.

Every case and situation is different and unique, requiring nuance and experience. Although challenging, prostate cancer recurrence after radiation is not a death sentence. If you are dealing with a similar situation, find out your options.

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