We have seen that there are many unanswered questions about focal thermal ablation (see this link), among them are:
- Is Index Tumor Theory valid?
- Can foci of cancer be precisely targeted using current imaging methods?
- Does thermal ablation completely ablate the cancer in the ablation zone?
- Will the Heat Sink Effect and biochemical protective mechanisms (e.g., heat shock proteins) always cause sub-lethal killing?
- Is toxicity and damage to organs at risk any better than radical (whole gland) radiation?
- How do the high "re-do" rates affect toxicity and costs?
- How do we track success?
- What are the best salvage therapies?
- Can it extend the time on active surveillance?
- What are the intra-operative risks?
- What is the learning curve like for therapists?
- Is it worth the cost?
- 15% were low volume GS 3+3 (cancer in ≤2 cores, <50% in any core)
- 23% were high-volume GS 3+3
- 60% were GS 3+4
- 3% were GS> 3+4
- 94% were T1c or T2a
- Median PSA=6.3
- 67% were intermediate risk (predominantly favorable)
- 33% were low-risk
- Median prostate volume was 40 cc.
- prophylactic antibiotics
- general anesthesia
- transurethral US heating wand
- pelvic tissue at apex avoided to avoid incontinence
- endorectal cooling device
- 243 minutes (4 hours), start to finish
- suprapubic catheter (17 days)
- Acute (immediate) Grade 2:
- erectile dysfunction (29%)
- UTI (25%)
- bladder spasm (10%)
- painful urination (10%)
- urinary retension (8%)
- pain (7%)
- incontinence (6%)
- epidydimitis (5%)
- Acute (immediate) Grade 3 (severe, requiring intervention):
- infection (4%)
- urethral stricture (2%)
- urinary retention (1.7%)
- urethral calculus and pain (1%)
- urinoma (1%)
- long-lasting Grade 2 adverse events:
- erectile dysfunction (23%)
- incontinence (3%)
- recurrent infections (2%)
- Sexual domain: 32%/ 1%
- ED on IIEF-15 questionnaire: 35%/6%
- 75% of previously potent men returned to erections sufficient for penetration with only ED meds.
- Urinary incontinence:14%/7%
- Urinary irritation/obstruction: 8%/5%
- Bowel domain: 5%/2%
Oncologic Outcomes (at 12 months):
- 35% had residual cancer at biopsy
- 24% among low volume GS 6
- 38% among high volume GS 6
- 37% among GS 3+4
- Median PSA reduced to 0.5 ng/ml
- Median prostate volume reduced to 2.8 cc
- PIRADS ≥3: 30%
There is little 12-month data available for other therapies, but recurrence rates almost always increase with time. There was a 2-year study of SBRT at Georgetown that may be roughly comparable:
Full-gland TULSA-PRO seems to treat PSA without eradicating the cancer (see this link). In about a third of favorable-risk patients, the cancer remained viable in spite of the thermal ablation. We see that compared to whole-gland SBRT, it is less curative, Severe (requiring intervention) acute urinary toxicity is higher with TULSA-PRO, although late-term Grade 2 urinary toxicity is lower (not severe for either therapy). Rectal toxicity is not an issue for either therapy. Potency preservation is good and about equal for both.
15-year study suggests long-term inferiority
Bründl et al. reported 15-year oncological outcomes of 674 patients treated with whole-gland HIFU at one university hospital in Regensberg, Germany. Notably, overall survival and prostate cancer-specific survival were high in all localized risk categories. However, comparing 15-year prostate cancer-specific survival to similar risk men who have undergone prostatectomy at Memorial Sloan Kettering, we see the survival is relatively poor:
15-yr Prostate Cancer-Specific Survival
* from the MSK pre-prostatectomy nomogram for a 62 yo man. For low-risk, he had PSA=5, GS 3+3, stage T1c, and 25% positive cores; For intermediate-risk, he had PSA=15, GS 4+3, stage T2c, and 50% positive cores; for high risk, he had PSA=25, GS 4+5, stage T3a and 100% positive cores.
The longest follow-up study there is for SBRT is 12 years. For SBRT, Alan Katz reported rates of "local control" on SBRT - the percent of patients who had recurrences only in the prostate. These could all theoretically be cured with a re-do of SBRT, focal brachytherapy or focal ablation. We can look at long-term local control from SBRT next to the long-term reported rates of salvage therapy after whole-gland HIFU (either re-do of HIFU or other salvage). HIFU does not compare well:
% patients who do not require salvage treatment
It is hard to see why anyone would choose HIFU or TULSA-PRO over SBRT. While focal ablation may incur less toxicity, the local recurrence rate will be much higher. These trials suggest that HIFU and TULSA-PRO are inferior, although only a direct randomized comparison could prove that definitively.
For an article discussing the use of focal ablation as an active surveillance "extender," see:
What should focal therapy be compared to and how does it compare?
For an article discussing salvage focal ablation after the failure of radiation therapy, see:
Focal salvage ablation for radio-recurrent prostate cancer