Half of long-term erectile function loss after brachytherapy is due to aging

Probably a difficult discussion for those who may be challenged translating words into multi-dimensional graphical representations…   HYPOTHESIS:   The age-related points from the OP seem to illustrate one key basis of why radiation therapy for PC is more frequently undertaken by elderly men versus younger men.   As background, I would acknowledge clearly that from the prior discussion that aging erodes potency over time for all men regardless of treatment (or no treatment).   This notion will be included in each of the two comments below, first about surgery, and second about radiation.   A second point of acknowledgement follows that the rates of erosion of potency due to radiation is less than rates of erosion due to aging, but for men undergoing RT those effects are additive, not “either/or.”   Surgery has a unique, complex side-effect profile; it may (with some reasonable liberties) be illustrated by a dominant pulse function followed by a right-sided decaying exponential.   The “pulse” occurs at the time of surgery, when virtually all patients are for at least a short period dysfunctional, and the decaying function illustrates the rate of potency improvement, which is weeks or months, or for some men years, and for a small number never recovers.   (This, too, is multi-variant, including notably surgeon skill and also notably age …younger men tend to recover faster.)   At some point, the opposite tendency of aging (counteracting the continued improvement over time during surgical recover) would cause an eventual reversal in the trend direction, shifting from negative (downward, if the y-scale is dysfunction) to flat and then eventually upward.   Of note, the upward trend (increased rate of dysfunction over time) from this point forward would be due to the slow decline from aging.   The radiation side-effect profile would look different graphically.   Any initial “pulse” function is much more muted compared to surgery—some have some initial ED, often minor, and others seem not to experience much.   The radiation side effect profile is more distinctly defined by the slow, steady erosion of performance over time.   The effect of treatment compounds the slow, steady erosion of performance over time caused by aging.   In both cases, the “line" on the graph represents sexual dysfunction over time for some representative individual…which is clearly not constant .   For each unique individual and set of circumstances, where those lines would lay or “cross” would be different.   If one’s outlook is 2-years out, the data is as presented in the links in this thread seems to provide a good “snapshot” of performance probability distributions for each treatment mode.     The longer the outlook, the closer the lines get together, or the more they diverge after they have crossed, supporting the hypothesis that the age-related points in this thread illustrate why radiation therapy is more frequently undertaken by elderly men.       Consideration of other late-term effects —particularly those treated by a Proctologist/GI practice—might tend to amplify the age-related considerations.    

Hahaha...chill Yoop. No effort to refute anything. Read it again (I realize it's complex).

No worries NK, not complex in the least - simply still not addressing the facts/data. Still.

Allen,    I see in the JAMA study you provided that at each age group —after only 2-years—the percent of patients with functional erections is higher for BT than other treatment modes. My previously posted hypothesis was more specific than that.   It explored a hypothesis to support the historic data that radiation/BT treatments are more frequently selected by elderly men than younger men, and specifically whether that selection may be due to concerns of the additional late-term effects caused by radiation (I considered only erectile dysfunction late-term effects)…and, very notably because younger men likely have an outlook longer than the 2-years reported in JAMA.   You replied with this comment:   “ The lines never cross. Surgery always has worse outcomes wrt ED compared to radiation for a guy starting out at the same age . ” Allen, I hear what you said, but I have not seen any data beyond the relatively near-term 2-year “snapshot.”   The hypothesis above presents logic that the surgery/radiation lines may cross after the near-term …a notable consideration for younger men.   What data supports your very unambiguous use of “ never ?”

Norm,

You seem somehow to have entirely missed the point, so I won't try to explain anymore - it seems to be pointless to do so. Suffice it to say that the lines can't cross because, as I keep saying, the deterioration from radiation occurs early and the age-related deterioration after surgery or radiation, occurs over the long-term. Two lines can't cross if they are starting at different places and the negative slopes afterwards are parallel. Parallel lines never meet.

The reason older men got radiation is historic, and is not much related to concerns about late-term effects, in fact the opposite. It's more because in the olden days, before dose escalation, radiation was not as curative as surgery. So only men with shorter life expectancy, or men who could not undergo surgery for some reason, were given radiation. It was felt that it would at least slow the progress of the disease, and they would die of something else first. At the same time, they wouldn't have to suffer from incontinence. I doubt that impotence, either treatment-related or age-related, even entered into the decision - although, I would argue that that is up to the patient - if he thinks it's important at 70, it is important.

- Allen

BTW, the two groups of men in the NEJM article I linked to—one group studied for 15-years following surgery, and the other followed for 15-years following radiation WHERE THE LINES DO CROSS—were not exactly the same age, but the medians were very close (65 & 69). Both were +/- 2 years of the average age of PC diagnosis of men in the US.

Hahaha…what irony!   There are so many poorly done studies out there that now we are frequently getting guidance on how to read and separate the high quality publications from the junk ones.   There’s several “checklists” out there which help laypersons understand which ones are more trustworthy.   Typical amongst the checklist items are these:   ·          Known, respected authors – Resnick, Penson, Hoffman, Albertson, etc…check ·          Supported by recent peer-reviewed journal articles – check; in fact, click on the list of 136 articles which have already cited this work ·          Preponderance of the evidence – check; in fact, the 2-year results are entirely consistent with the results of the JAMA article linked by Tall Allen...after 2-years, ED amongst surgery patients was worse than radiation patients.  (I'd guess you're probably ok with that part of the results!) ·          Descript ion of the statistics used – check ·          Self identification of possible bias/shortcomings – so what you wrote, Jim, is basically an enumeration of that the authors already self identified…only you’re using their list as a reason to throw the results out!    What irony!!

I just ignore - it serves no purpose to respond.

I'm reviving this thread because I just got some interesting feedback on the article from a distinguished radiation oncologist. He corrected me that the data set no longer resides at UMich (which he recently left). More importantly, he offered the following comments:

Daniel Hamstra said...
I think your comments about age adjusted EPIC scores are important... I think you caught the main difference between surgery and RT modalities such that this statement:
“In 2011, Alemozaffar et al. (see The “New” Prostate Cancer InfoLink commentary) reported comparable figures on erectile function at 2 years after surgery (RP), external beam radiotherapy (EBRT), and brachytherapy (BT).”
although factually true, was a “positive spin” that the urology authors placed on this analysis. Those of us who are in RadOnc tried to fight it, but all we really could get was having them put the gross numbers in without making any adjustments for either age (which would affect baseline function and decline over time) and baseline function.

Because of age and patient selection, the men who underwent RP had better sexual function to begin with. Prior to treatment 83% of men getting RP did NOT have sexual dysfunction by the EPIC while this number was 67% for brachytherapy and 53% for EBRT. These numbers also parallel the age differences with RP << BT < EBRT. However, at two years, preserved sexual function was found in 37%, 43%, and 43% (RP, BT, EBRT). So, for those with sexual function prior to treatment, even after adjusting for age, RT (of either sort) preserved function much better, which was 45% preservation for RP, and 64% for BT, and 70% for EBRT. After adjusting for age, the difference with either RT modality was even greater.

The timing of decline of sexual function, as you noted, is also not what people usually report for RT. I'm not sure where the "old wives tale" came from. But what is always talked about is that RP causes an immediate decline with a slow recovery for 1-2 years while RT shows a stability initially with a slow decline over 2 years. I think, as you noted, studies like PROSTQA, Katz, and the BC brachytherapy study all seem to support that with RT the decline is much faster (often even in the first several months) with some patients later having a modest recovery, and then all followed by the relentless (likely age induced) decline over time.

This is frankly what others had seen previously but somehow the wives tale stood. See for instance:

Time of decline in sexual function after external beam radiotherapy for prostate cancer.

Their first time point was 6 months, and by this point about half the decline they were going to see had already occurred.