Thursday, August 31, 2017

The myth that younger men should not pursue active surveillance

In spite of no evidence to back up their assertion, I continue to hear urologists say things like "If you were older, I'd recommend active surveillance. But because you're young, you should have surgery for your low risk prostate cancer now while your recovery will be better." We saw, in a previous article, that immediate surgery rather than active surveillance only resulted in more years of expected misery from impotence and incontinence: see: "Can a man be too young for active surveillance?"

Now, a new study from Memorial Sloan Kettering Cancer Center examines the evidence for potency preservation. The authors, who include John Mulhall, the sexual medicine specialist, demonstrate that the expected loss of erectile function is never compensated for by better recovery in younger men and the age-related decline in erectile function over the years while waiting on active surveillance.

They used a standard questionnaire, the International Index of Erectile Function 6 (IIEF6). It is sometimes called the Sexual Health Inventory for men (SHIM). There are six questions, and the best score (excellent erectile function) is 30. The questions are:

1. Over the last month, how often were you able to get an erection during sexual activity?
2. Over the last month, when you had erections with sexual stimulation, how often were your erections hard enough for penetration?
3. Over the last month, when you attempted intercourse, how often were you able to penetrate your partner?
4. Over the last month, during sexual intercourse, how often were you able to maintain your erection after you had penetrated your partner?
5. Over the last month, during sexual intercourse, how difficult was it to maintain your erection to completion of intercourse?
15. Over the last month, how do you rate your confidence that you can get and keep your erection?

All men filled out the questionnaire before surgery and periodically for two years. They excluded high risk patients who wouldn't be eligible for active surveillance, and any men who did not have bilateral nerve-sparing surgery. Men who had hormone therapy or salvage radiation were also excluded. There were 1,103 men in their cohort of men treated with RP at MSKCC between 2009-2013. Needless to say, MSKCC has some of the best, most experienced surgeons in the world.

They first looked at the baseline scores by age to get an understanding of how erectile function declines with age. This defines the expected erectile function if there were no surgery. They also looked at actual scores after surgery for each age. The difference between actual and expected shows the true effect of surgery on erectile function, with compensation for age-related decline and for the time delay caused by active surveillance.

They found that:

  • Each year increase in age reduced the IIEF6 score by -0.27
  • Erectile function recovery after RP declined by -0.16 for each year older at the age of treatment

While younger men started with a higher erectile function score, and their recovery after RP was better, it was never good enough to be better than the erectile function of an older man who didn't have surgery. At all time points, they would have been better off if they had delayed treatment and stayed on active surveillance. There was no "window of opportunity" where younger age recovery exceeded what would be expected to happen if they waited.

The authors conclude:
Small differences in erectile function recovery in younger men are offset by a longer period of time living with decreased postoperative function. Better erectile recovery in younger men should not be a factor used to recommend immediate surgery in patients suitable for active surveillance, even if crossover to surgery is predicted within a short period of time.

I hope patients whose urologists spout the myth that "early surgery will lead to better long-term erectile function than delaying until he is older" will email this important study to them and ask for comment.

Monday, August 28, 2017

After failure of first-line radiation, both kinds of salvage brachytherapy are equally effective

A group of researchers at Memorial Sloan Kettering Cancer Center (MSKCC) reported in 2014 (see this link) on the outcomes of 42 patients with radio-recurrent prostate cancer treated with salvage high dose rate brachytherapy (sHDR-BT). The results were quite good - over two thirds had no evidence of further recurrence as of 5 years, and grade 3 toxicity (serious, requiring treatment) was limited to one patient with late-term urinary incontinence. Kollmeier et al. have now updated their results and compared them with outcomes of men treated with salvage low dose rate brachytherapy (sLDR-BT).

All patients were treated between 2003 and 2015, and all salvage treatments were whole gland, not focal or hemi-gland.

  • 37 patients received sLDR-BT
  • 61 received sHDR-BT
  • 45% received adjuvant androgen deprivation therapy (ADT)
  • All patients were screened for distant metastases with a CT or MRI and a bone scan at least
  • All patients had biopsy-confirmed cancer in the prostate

After a median follow-up up 31 months:

  • 3-year PSA relapse-free survival (RFS) was 60%
  • Both therapies were similar
  • RFS=39% for those with PSA doubling times (PSADT) less than 1 year vs. 72% for those with PSADTs of a year or more.
  • No statistically significant differences in urinary or rectal toxicity between the two therapies: most returned to baseline function.
  • sLDR-BT had a higher rate of acute urinary toxicity
  • Erectile function was not measured because of high rates of pre-existing impotence and ADT usage

In the Fuller study of salvage SBRT (see this link), bRFS was 82% at 2 years, and ADT was not used. NIH will soon begin recruitment for a clinical trial of salvage SBRT (NCT03253744), which includes detection using the DCFPyL PET/CT - the best of the new generation. Dr. Kollmeier mentioned that MSKCC has treated a few select patients with salvage SBRT as well. They are also looking at using a more tailored approach: adding systemic therapy for higher grade recurrences and focal/hemi-gland treatment for less aggressive cases. MSKCC is on the leading edge of using the new generation of PET/MRI scans which will undoubtedly improve patient selection going forward.