Wednesday, March 17, 2021

Whole gland TULSA-PRO outcomes: Is it time to give up on thermal ablation for prostate cancer?

 We have seen that there are many unanswered questions about focal thermal ablation (see this link), among them are:

  1. Is Index Tumor Theory valid?
  2. Can foci of cancer be precisely targeted using current imaging methods?
  3. Does thermal ablation completely ablate the cancer in the ablation zone?
  4. Will the Heat Sink Effect and biochemical protective mechanisms (e.g., heat shock proteins) always cause sub-lethal killing?
  5. Is toxicity and damage to organs at risk any better than radical (whole gland) radiation?
  6. How do the high "re-do" rates affect toxicity and costs?
  7. How do we track success?
  8. What are the best salvage therapies?
  9. Can it extend the time on active surveillance?
  10. What are the intra-operative risks?
  11. What is the learning curve like for therapists?
  12. Is it worth the cost?
Laurence Klotz et al. conducted a clinical trial of a new kind of high-intensity focused ultrasound (HIFU). He studied whole-gland ablation because current FDA rules only permit ablation for removal of prostate tissue (like a TURP), but not for treatment of prostate cancer. In fact, the FDA specifically rejected HIFU for the treatment of prostate cancer. 

TULSA-PRO utilizes a thermal feedback loop to assure that tissue temperature reaches the desired heating. It is done "in-bore" in an MRI by a team consisting of a urologist and an interventional radiologist, and an anesthesiologist (full anesthesia was required). It was hoped that the MRI precision and assured tissue heating (to 55°C) would afford higher cancer-killing with less toxicity.

115 patients were carefully selected:
  • 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.
The operative procedure involved:
  • prophylactic antibiotics
  • general anesthesia
  • cystoscopy
  • 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)

Safety Outcomes/ Adverse Events:

Physician-reported outcomes:
  • 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%)
Patient-reported outcomes at 12 months vs baseline on EPIC questionnaire (% reporting moderate decline/ % reporting moderate gain):
  • 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:



TULSA-PRO (1 year)

115 patients

SBRT (2 years)

100 patients

Risk category

Low-risk

Intermediate-risk

High-risk


33%

67%


37%

55%

 8%

Biochemical recurrence-free survival

100%

99% (1 local recurrence in a high-risk patient)

Biopsy-proven local recurrence

35%

1% estimated in the high-risk patient

Nadir PSA

0.5 ng/ml

0.5 ng/ml

Acute urinary toxicity (grade 3)

8%

0%

Acute rectal toxicity (grade 3)

0%

0%

Late-term urinary toxicity (grade 2+)

5%

18% 

(1% Grade 3)

Late-term rectal toxicity (grade 2+)

0%

0%

Potency preservation among previously potent men

75%

79%


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.

It is hard to see why anyone would choose TULSA-PRO over SBRT. While focal ablation may incur less toxicity, the local recurrence rate will be higher. This trial suggests that  TULSA-PRO is inferior, although only a direct randomized comparison could prove that.

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



5 comments:

  1. Not sure that I follow the second line in your chart. Shouldn't the biological recurrence-free survival be 65 percent for TULSA-PRO?

    - ASAdvocate

    ReplyDelete
    Replies
    1. No. It is BIOCHEMICAL recurrence-free survival (i.e., PSA), not "biological." PSA didn't increase, but the cancer remained.

      Delete
    2. Allen -

      will you be posting this on Healthunlocked?

      Delete
    3. I posted a link there yesterday.

      Delete
  2. Thanks, Allen. This is a sobering read. All of us on AS appreciate your bringing these studies to a wide audience.

    ReplyDelete