Wednesday, October 26, 2016

Lu-177-PSMA-617: Another update

Because there is great interest in systemic therapies for metastatic prostate cancer, I want to provide readers with the latest news about the Lu-177-PSMA-617 trials in Germany.

I recently reported (see this link) on 74 patients – 31% had PSA declines greater than 50%. A new report by Rahbar et al. expands the patient base to include PSA data on 99 patients and toxicity data on 121 patients treated at 12 therapy centers.  After median follow-up of 16 weeks, and up to 4 therapy cycles:
·      45% had a PSA decline greater than 50%
o   40% after a single cycle
·      18/121 patients (15%) had serious or life-threatening hematotoxicity, affecting red blood cells (10%), platelets (4%), and white blood cells (3%)
·      Xerostomia (loss of saliva) occurred in 8%

This is a very encouraging PSA response. For comparison, only 13% had a PSA reduction greater than 50% in the Xofigo clinical trial. However in that trial, 66% had a 50%+ decline in bone alkaline phosphatase, which may be a better biomarker for bone metastases. The hematotoxicity was identical.

What we really want to know is whether the treatment increases survival, and whether it is any better than Xofigo in doing so. The potential benefit of Lu-177-PSMA-617 is that it can treat non-osseous metastases too. We await future clinical trials to prove its benefit.

Monday, October 3, 2016

Urinary and sexual healing improved by waiting to start salvage radiation

Salvage radiation adds to the side effects of surgery and may halt the progress made towards healing. Healing takes time. On the other hand, we have learned that adjuvant or early salvage radiation has better oncological outcomes than waiting, the earlier the better (see this link).  Two new studies help us better understand the trade-offs.

Zaffuto et al. examined the records of 2,190 patients who had been treated with a prostatectomy. Their urinary and sexual outcomes were evaluated based on whether they received:
  1. no radiation
  2. adjuvant radiation (prior to evidence of recurrence, usually administered 4-6 months following prostatectomy), or
  3. salvage prostatectomy (after PSA reached 0.2 ng/ml)

They also looked at outcomes based on when they were treated with radiation:
  1. Less than a year after surgery, or
  2. A year or more after surgery

With median follow-up of 48 months, the 3-year outcomes were as follows.

Erectile function recovery rates were:
  • 35.0% among those who received no radiation
  • 29.0% among those who waited to receive salvage radiation
  • 11.6% among those who had adjuvant radiation
  • 34.7% among those who waited for a year or more before initiating salvage radiation
  • 11.7% among those who had radiation within a year

Urinary continence recovery rates were:
  • 70.7% among those who received no radiation
  • 59.0% among those who waited to receive salvage radiation
  • 42.2% among those who had adjuvant radiation
  • 62.7% among those who waited for a year or more before initiating salvage radiation
  • 43.5% among those who had radiation within a year

Van Stam et al. looked at their database of 241 patients who were treated with salvage radiation and 1005 patients who only received a prostatectomy but no radiation afterwards. All patients were last treated between 2004 and 2015, and had up to 2 years of follow-up afterwards.

After adjusting for patient characteristics, they found that:
  • Salvage radiation patients had significantly worse recovery of urinary, bowel, and erectile function.
  • Patients who waited more than 7 months before receiving salvage radiation had better sexual satisfaction scores and better urinary function recovery.

So what is one to do: treat earlier for better odds of cancer control, or treat later for better urinary and sexual function recovery? We have seen that adjuvant radiation is rarely likely to be necessary, and that early salvage radiation can probably be just as effective. But what if PSA is already high and rising rapidly? One solution might be to use hormone therapy to halt the cancer progression while tissues heal. That may help with urinary function, but is apt to interfere with recovery of sexual function. This remains a difficult decision, which is why discussions with an experienced radiation oncologist should begin at the earliest detectable PSA (over 0.03 ng/ml) on an ultrasensitive test. Most of all, the patient must do the self-analysis to understand which trade-offs he is willing to make.

Sexual function was no worse when fewer external beam radiation treatments were used

The HYPRO trial was designed to detect whether hypofractionation (fewer radiation treatments) was inferior to conventional fractionation. Their previous report looked at outcomes on late-term urinary and rectal function. Here, they report on sexual function outcomes.

To briefly recap, 820 intermediate/high risk patients were randomly assigned to one of two external beam radiation treatment protocols:
  • Conventional fractionation: 78 Gy in 39 treatments
  • Hypofractionation: 64.6 Gy in 19 treatments
  • 39% had adjuvant hormone therapy lasting up to 6 months

It should also be noted that men were 71 years of age at the time of treatment.

After median follow-up of 37 months:
  • Among those with partial or full erectile function at baseline, erectile dysfunction occurred in 34.4% among those who had hypofractionation and 39.3% among those who had conventional fractionation. The difference was not statistically significant.
  • Orgasmic function among those who did not have hormone therapy was higher for the hypofractionation group. The difference was statistically significant.
  • Overall, sexual function scores declined after treatment, but there was no difference between two treatments.

Two other randomized clinical trials also reported no difference in sexual function. Both the Fox Chase trial (see this link) and the M.D. Anderson trial (see this link) found hypofractionation made no difference in sexual outcomes. This should give some comfort to patients and radiation oncologists considering hypofractionation.