Originally published 10/7/2022
When prostate cancer (PCa) patients have had whole-gland radiation as their primary treatment, it is estimated that 20-40% of cases will have biochemical recurrence (rising PSA).[i]
If biopsy and imaging diagnose a localized tumor, localized salvage treatment with intent to cure is an option for qualified patients—but doctors should discuss the risks with patients.
As of April 1, 2024 the established guidelines for treating localized prostate cancer (PCa) recurrence after radiation offer important points:
- Emphasize that there are likely to be higher risk of treatment-related adverse events, particularly impacting patients’ urinary, sexual, and bowel function…”
- Salvage ablation applying cryoablation or HIFU are modalities that traditionally have been applied as whole-gland treatments, although these may also be performed as partial gland ablation or focal ablation.
Note that the guidelines identify both cryo (freezing) and HIFU as salvage therapies that can be done focally for meticulously qualified patients.
What about Focal Laser Ablation (FLA)? A 2023 paper by Manenti, et al. reports 5 cases of radiation recurrent PCa that were treated with transperineal laser ablation (TPLA) as a focal treatment.[ii]
(NOTE: The Sperling Prostate Center uses the transrectal FLA approach, which is more common than transperineal. Also, in this case report the treatment was delivered under fusion guidance, whereas our Center uses real time in-bore MRI guidance which offers superior accuracy over fusion).
The Manenti report states that there were no instances of recurrence during the 18-month follow-up period which included “…regular PSA sampling, 3T mpMRI, and ultrasound/MR fusion-guided biopsies systematic and targeted at the site of the focal treatment.”
For the duration of their follow-up period, they found that their approach to FLA offered effective PCa control without complications or side effects.
“I’m sorry to say your prostate cancer has recurred.” No one wants to hear that message after an initial whole-gland treatment like surgery or radiation. It means their prostate cancer (PCa) is back. Sadly, at this time there is no treatment that offers a guaranteed cure. While 5-year survival rates for localized PCa approach 100%, over the longer term as many as 20-40% of patients will experience recurrence.
Recurrence after radiation treatment offers a unique opportunity. Unlike surgical gland removal, radiation leaves the treated tissue in place. If the recurrence is still contained in the radiated gland, it’s called localized recurrence, with the potential for a localized treatment. Tests are done to confirm localization, and to rule out regional and distant metastasis (spread). Both biopsy and advanced imaging like multiparametric MRI (mpMRI) and/or PSMA PET/CT scans can be done to evaluate the pelvic bed, nearby lymph nodes, and even the full body for evidence of PCa colonies beyond the prostate.
Once localized disease is confirmed, a salvage treatment can be considered. Just as the primary or initial treatment was intended to be definitive—that is, completely control PCa with no retreatment needed— salvage treatment also has potential to be definitive. There are five choices:
- Salvage prostatectomy – This is a complicated surgery due to radiation-related scar tissue and anatomic distortions. There is a higher risk of urinary, sexual and bowel side effects.
- Salvage radiation – While adding more radiation is theoretically possible, most experts don’t recommend it because of later onset urinary, sexual and bowel side effects, and an increased risk of secondary pelvic/bowel cancers.
- Salvage ablation – For most patients who are candidates for a minimally invasive procedure, this is the treatment of choice. There are three current whole-gland ablation methods, cryotherapy (freezing), HIFU (focused ultrasound), and TULSA (transurethral HIFU). Since they are all image guided, the treatment accurately encompasses the whole gland plus an extra margin of tissue to pre-empt PCa from escaping into neighboring tissue. While the side effect risks are greater than primary ablation, they are significantly less than salvage prostatectomy or salvage radiation.
- Androgen deprivation therapy (ADT) – Many radiation recurrent patients are not candidates for a local salvage treatment, usually due to co-existing medical conditions or less than 10 years’ life expectancy. Such patients can be put on medications to deprive the PCa tumor of testosterone. ADT puts the brakes on the tumor but is not curative; when ADT no longer works, options include chemotherapy and immunotherapy combinations.
- Active surveillance (AS) – Rather than immediate treatment, the patient can be put on a monitoring protocol that includes imaging, PSA tests, and repeat biopsy. Choosing AS depends on the tumor’s clinical factors, the patient’s overall health, and patient preference. The risk is missing a window for a local salvage treatment if the cancer begins to spread.
Focal ablative salvage therapy (FAST)
More recently, there is a growing body of research on focal salvage therapy to target just the identified tumor. This approach is called Focal Ablative Salvage Therapy, or FAST. Thanks to mpMRI and MRI targeted biopsy, the tumor’s location, extent, aggressiveness (grade) and genomics can be identified. Ablating just the tumor offers the dual advantage of cancer control plus low side effect risks. As with whole-gland primary treatment, the same three ablation methods (cryo, HIFU, TULSA) can be used.
As of this writing, the most recent data was presented at the 2022 annual meeting of the American Urological Association by Dr. Deepika Reddy (National Health Service, London)[iii]. The statistics were drawn from 288 consecutive cases of radiation recurrence that were treated with either focal HIFU (221 patients) or focal cryo (67 patients). (Although treatment using TULSA was not included in this study, a published paper reports on salvage customized TULSA with a small group of radiation recurrent PCa patients.[v]) According to Dr. Reddy’s presentation, 265 patients had pertinent follow-up records for analysis. Patients had either stage T2 or T3 disease, and Grade Group 2, 3 or >3.
Treatment was deemed successful based on failure-free survival (FFS, no evidence of recurrence) and retreatment-free survival (RFS, or no additional treatment). The numbers are very encouraging, with 77% success rates for both FFS and RFS at 6 years post-FAST. About 7% of patients had adverse events following ablation, most of which were urinary infections. These patients avoided the surgical trauma of salvage prostatectomy, the increased cancer risk of salvage radiation, and the likely side effects of both.
What about using Focal Laser Ablation (FLA) for FAST? A very small but hopeful study (3 patients) gives short-term results for targeted FLA after HIFU recurrence. The authors report that it is “…feasible in the salvage setting with promising short-term oncologic outcomes and with the potential to preserve functional outcomes…”[iv] i.e., urinary and sexual capabilities. This early paper has positive implications for treating radiation recurrence with FLA. We’ll be watching for more studies on salvage FLA. For now, FAST is a new standard of care for radiation recurrent PCa that we can all be thankful for.
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] Simon NI, Parker C, Hope TA, Paller CJ. Best Approaches and Updates for Prostate Cancer Biochemical Recurrence. Am Soc Clin Oncol Educ Book. 2022 Apr;42:1-8.
[ii] Manenti G, Nezzo M, Ryan CP, Fraioli FR, Carreri B, Gigliotti PE, Angeloni C, Di Pietro F, De Angeli M, Perretta T, D’Angelillo RM, Garaci FG. Transperineal laser ablation (TPLA) with ultrasound/MRI fusion guidance in the treatment of localized radiotherapy-resistant prostate cancer. BJR Open. 2023 Oct 18;5(1):20230042.
[iii] Ira, Vanessa. “Focal Ablative Salvage Therapy is Safe, Effective for Recurrent Prostate Cancer.” GU Oncology Now, May 18, 2022. https://www.docwirenews.com/gu-oncology-now/gu-conferences/aua-2022/focal-ablative-salvage therapy-is-safe-effective-for-recurrent-prostate-cancer/
[iv] Lumiani A, Samun D, Sroka R, Muschter R. Single center retrospective analysis of fifty-two prostate cancer patients with customized MR-guided transurethral ultrasound ablation (TULSA). Urol Oncol. 2021 Dec;39(12):830.e9-830.e16.
[v] Magee D, Perlis N, Corr K, Chan R et al. Salvage interstitial laser thermal therapy under MRI guidance (MRgFLA) for high-intensity focal ultrasound (HIFU) recurrences: feasibility study. Clin Imaging. 2021 Aug;76:217-221.
About Dr. Dan Sperling
Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.
