Showing posts with label bounces. Show all posts
Showing posts with label bounces. Show all posts

Thursday, March 15, 2018

Bounces after Primary Radiation Therapy

Perhaps the single most annoying "side effect" of radiation is not a side effect at all; it's the periodic fluctuations in PSA, called "bounces," that can occur for years after therapy. A new analysis from Memorial Sloan Kettering assures us that our anxiety is misplaced -- PSA bounces predict better cancer control.

Romesser et al. reported on a retrospective study among 776 patients treated from 1990 to 2010 with dose-escalated external beam radiation therapy. The median radiation dose was 81Gy. None received adjuvant ADT. They defined a bounce as a PSA rise ≥ 0.2 ng/ml but less than 2.0 ng/ml above the lowest level (nadir) it had reached thus far, followed by a decrease to as low or lower than the previous nadir. After a median follow-up of 9.2 years, they found:

  • 16% of patients had a bounce
  • The bounce occurred after a median of 24.6 months
  • It was a median of 0.37 ng/ml over the previous nadir

Bounces were more likely to occur in patients who:

  • were younger (see this link)
  • had a lower Gleason score
  • were lower  T stage
  • received a higher radiation dose

At 8-years follow-up, they reported that bounces were associated with:

  • Greater time to reach ultimate PSA nadir (43 months vs 26 months) 
  • Lower risk of PSA relapse (9% vs 29%)
  • Decreased risk of metastases (1% vs 10%)
  • Decreased prostate-specific mortality (0% vs 3%)
  • Decreased overall mortality (6% vs 11%)

Very similar findings have been reported for other forms of radiation: SBRT, Low Dose Rate Brachytherapy (seeds), High Dose Rate Brachytherapy, and Brachy Boost Therapy. A 2004 study of EBRT and bounces found an inverse correlation between bounces and PSA relapse-free survival. The difference is probably attributable to much lower radiation dose (only 1% received > 78 Gy) and because the higher risk men were treated between 1986 to 1995, mostly before PSA testing became prevalent.

The percent of men who experience a bounce ranges from 15%-50%, and depends on how the researchers define a bounce. It ranges from a minimum of  0.1- 0.8 ng/ml above previous nadir in most studies. Bounces are often above +1 ng/ml, may last for more than a year, and are usually noted between 1 year and 4 years after therapy.

The reason that bounces occur is a bit of a mystery. There are various theories:

  • Prostatitis - either pre-existing, arising after invasive procedures (e.g., biopsy, fiducial placement, or brachytherapy), or induced by radiation.
  • Immune infiltration: after radiation releases cancer antigens, T cells are activated to eventually attack the remaining cancer in the prostate (see this link).
  • Cancer cells that have been dormant, eventually emerge and undergo "mitotic catastrophe."
  • Delayed apoptosis (cell death) among late-responding healthy cells
  • PSA drops most sharply and consistently in more aggressive cancers because radiation kills the most rapidly dividing cells first.
  • PSA measurement variation (e.g., different test kits, different labs, natural fluctuations)

Whatever the reason, bounces are a good thing. For patients that were diagnosed with low or intermediate risk prostate cancer, a slow, bouncy PSA decline should engender a feeling of relief rather than anxiety. But what of the unfavorable risk patient with bounces so high that they approach or exceed +2.0 ng/ml and stay elevated? While recurrences usually occur later than bounces, is there a method available for early detection of a local recurrence? Biopsies are invasive and non-informative while the cancer is still in the "slow death" phase. However, there is a kind of MRI called MR Spectroscopy (MRS) that may be able to non-invasively distinguish between bounces and PSA recurrence. In a pilot study (and this one), the researchers found that the MRS-detected choline/citrate ratio might be markedly elevated and focal if the cancer is metabolically active, but low and diffuse if there is only benign inflammatory activity.

Tuesday, August 30, 2016

Another reason to love your bounces

PSA bounces after primary radiation therapy are a common phenomenon, occurring in a quarter to a third of patients. While some men might prefer to see an uninterrupted PSA decline after treatment, studies have demonstrated an association with improved cancer control. Studies also find higher incidence of bounces in younger men. Perhaps related to that, we now see that there is an association between bounces after brachytherapy and erectile function, sexual activity, and sexual satisfaction.

Matsushima et al. examined the records of 154 patients who had been treated with brachytherapy, and whose sexual function was self-assessed at baseline and continually for up to 3 years. Among those men, 25% experienced a PSA bounce of at least 0.4 ng/ml above the previous PSA reading, and they experienced that bounce a median of 18 months after therapy.

Compared to the men who did not have a bounce, those who did reported higher scores on all measures of sexual performance at baseline and at all time points afterwards. “Bouncers” had higher scores on:
  • ·      Erectile function
  • ·      Orgasmic function
  • ·      Sexual desire
  • ·      Intercourse satisfaction
  • ·      Total International Index of Erectile Function-15 Score

The authors also conclude: an occurrence of prostate-specific antigen bounce seems to be more likely in those who are more sexually active.”

While it’s tempting to infer causal relationships, there are many possible reasons for this observation. It’s possible to put forward many hypotheses, none of which are proven:
  • ·      Younger men have better sexual performance, and it may just be a coincidence that they are more likely to have bounces.
  • ·      Because PSA readings are affected by recent sexual activity, those with bounces had sex closer to the date of their PSA test.
  • ·      Sexual activity promotes health of the sexual apparatus, and deters radiation-induced scar-tissue formation.
  • ·      Older cells may be more prone to immediate killing by radiation, while cell-cycle arrest, which may delay apoptosis, may be more likely in younger cells.

Whatever the reason behind the association, it provides one more reason not to worry about bounces after radiation therapy.