A review of PET Imaging for Recurrent Prostate Cancer

This is a quite informative paper from Practical Radiation Oncology, giving a good overview of the newer imaging technologies being developed to identify the location of recurrent prostate cancer before beginning salvage radiation therapy.

Prostate cancer–specific PET radiotracers: A review on the clinical utility in recurrent disease

I’ll comment in a separate post on where my head is at after receiving my latest PSA results.

Day 2,948 – PSA Results

My slight sense of optimism that I gained after my last consistent PSA result was shattered at four o’clock this morning when I hopped online in a fit of insomnia to check my PSA test results from this week. I’m back on the upward climb again with a PSA of 0.13 ng/ml.

PSA 20181203 clean

My spiffy spreadsheet predicted a value of 0.129 ng/ml, so it wasn’t unexpected. Just my hope for a more stable PSA went out the window.

Obviously, I’ve got some serious thinking to do in the weeks ahead.

The predictive part of my spreadsheet shows the increase will continue at a rate of about 0.011 ng/ml every four months. In April, I would be at 0.140 and in August at 0.151. Is that rate slow enough to delay any decision about salvage radiation therapy a while longer? I don’t know.

Do I get involved with the imaging trial at UCLA to see if we can determine where the cancer is before undergoing salvage radiation therapy? I don’t know.

Or do I just say screw it and start the salvage radiation therapy in early 2019? I don’t know.

Stay tuned for the answers. That, or for pictures of ostriches with their heads buried in the sand.

Day 2,841 – A Chat with the Urologist

I met with the urologist this afternoon to go over my 1 August 2018 PSA test results and it was an interesting conversation.

This was a new guy wearing his spiffy white lab coat with the University of California-San Diego (UCSD) emblem embroidered on the pocket. (I pretty much see a different doctor each time I go to the VA hospital and, yes, UCSD doctors care for patients at the VA hospital, too.) I had my PSA trend chart printed and sitting on his desk when he walked in, which he appreciated seeing the whole history on one page.

I let him start the conversation and it was pretty clear right from the start that he was of the “continue to monitor; no need to act right away” mindset. He really focused on my PSA doubling time being so long as being the reason for his recommendation to just watch this for now.

I shared my conversation with the radiation oncologist with him and he really didn’t comment one way or the other about the R.O.’s initial recommendation to zap.

I did take advantage of the opportunity to discuss the urological side effects of being zapped in salvage radiation therapy. One of the things that I focused on was urinary strictures.

He explained that just by having a prostatectomy and stretching the bladder neck to reconnect with the urethra, you’re in essence creating a stricture to begin with. “That’s a good thing,” he said, “because it helps control the urine flow in the absence of the prostate.” But zapping the area will change the nature of the surrounding tissue and can cause it to close down further. If that’s the case, they may have to do a procedure to re-open things and that’s where you can get into the higher leakage scenarios.

One of the things that really resonated with me during that discussion about side effects was when he said that I shouldn’t even be worried about them because I could go months or years without even having to think about salvage radiation therapy. (And, no, I didn’t prompt him to say that!)

That led to a discussion about the newer imaging technologies and he reinforced what I already knew—that most are unreliable with PSAs less than 0.2 ng/ml. I told him that the spreadsheet that generated my chart shows that I won’t hit 0.2 until late 2020 or early 2021 if it continues at its current pace. Perhaps in that time, the new imaging technologies will be better and more reliable at lower PSA levels. (He was also empathetic to the idea of not zapping unless you knew where the cancer was.)

We also talked about the frequency of my PSA tests and his immediate response was that we could do this every six months, again, based on my PSA doubling time. That surprised me. We’ve been on a four-month cycle for three years now. He said it would be my call, so I opted to stick to the four-month cycle for at least one more cycle.

Wrapping up the conversation, I did ask, “If I do have to get zapped at some point, where would you do it? UCSD or Naval Medical Center?” He deflected my question and never responded, so I asked again. Again, he remained silent but his hint of a grin perhaps answered it for me.

All in all, I was pleased with the consult and am content to continue to monitor, with my next PSA test being in early December.

Yes, I know that more studies are showing that zapping recurrent prostate cancer early leads to better outcomes in the long run. But other studies (Pound, Freedland) show that someone with my pathology can delay or even forego additional treatment and its associated side effects impacting quality of life and stick around for an additional 8-15 years. So, yes, this is a bit like playing a game of chicken or Russian roulette, and that thought never leaves my mind.

So why not get zapped and be done with it? Because quality of life is very important to me and if I can maintain it for a few years more than I want to try and do that. Is there risk of the cancer getting away from me? Of course. But with continued monitoring and perhaps advances in imaging technology, we can stay one or two steps ahead of it.

Time will tell.

Day 2,827 – Q&A with the Radiation Oncologist

Just a quick update…

I shared my last PSA results with my radiation oncologist via email yesterday to see if the results would influence his treatment recommendation.

He stated that a stable PSA is “great news” and that “continuing to monitor at this point is a very reasonable approach.” I also asked if a four-month PSA test frequency was appropriate or if we should look at increasing the frequency. With my numbers, he said that a three to six month frequency was most common, so sticking to four months was fine.

I also asked for clarification about sexual function after salvage radiation therapy. For some reason, I had it in my mind that from our conversation during the initial consult, he said that zapping me would likely damage my one remaining nerve bundle to the point that sexual function would be a thing of the past. He corrected me.

He said that post-radiation function is highly dependent on pre-radiation function. There will likely be some degradation, but not necessarily a complete loss of function as I had somehow lodged in my brain.

He closed the conversation by saying, “Hopefully your PSA will continue to behave itself and we can worry about that [sexual function] down the road.”

Needless to say, I was quite pleased with those responses.

We’ll see what the urologist says on the 21st (I put the wrong date in my last post) but, for now, I’m fine with doing nothing until my next PSA test in December.

 

Day 2,758 – Heads or Tails

IMG_5341That’s what it’s coming down to, or so it seems. Using the ultimate “executive decision-making aid” to determine what I’m going to do.

What brought this on? Another email exchange between me and my radiation oncologist.

Over the weekend, a few more questions popped into my head and I wanted to get his response. Yesterday, I fired off an email asking if any advances in radiation delivery technology or methods in the last 10-15 years improved the side effect outcomes over the studies he shared with me. In short, the answer was no—there were no appreciable changes.

Of greater interest to me was his interpretation of the Freedland study, which shows that I can do nothing and have a 94% chance of being around 15 years from now. His response:

I am familiar with the study you included, and it is one of many retrospective reviews on this subject. The authors preformed a retrospective review on a total 379 patients over period of 18 years from 1982 – 2000. Therefore, although the data are valuable and contribute to the literature, I consider it (as well as the many other studies on this subject) thought provoking.

Perhaps I’m reading too much between the lines, but his last sentence translates into “skeptical of the study” to me. He continued:

The bottom line is that you have a biochemical recurrence with a low, slowly rising PSA.  Do you need radiation treatment now, sometime in the future or never?  I don’t have a definitive answer to that question, but there are data to suggest “the earlier the better” and other data to suggest treatment might not be needed at all.  It depends on your point of view…

Am I upset by that response? Not really. It’s pretty much what I expected it to be, and that tells me that my research has been quite thorough. He and I both landed at the same place.

Will it make deciding my course of action any easier? Hell no. But it does reinforce that it’s my decision, and my decision alone.

Now where did I put those Eisenhower dollar coins again???

Day 2,754 – Researching Salvage Radiation Therapy—Again

It’s 7:30 p.m. on the Saturday of a three-day holiday weekend in the United States, and I’m reading articles on salvage radiation therapy. Who said prostate cancer wasn’t fun?!?

I did come across this informative article from the Journal of Clinical Oncology published in May 2007:

Predicting the Outcome of Salvage Radiation Therapy for Recurrent Prostate Cancer After Radical Prostatectomy

The authors set out to create a nomogram that predicted the “probability of cancer control at 6 years after SRT for PSA-defined recurrence,” and they speak at length about the variables used in their nomogram, as well as its limitations.

I plugged my stats into their nomogram and came up with a 70% probability that I won’t see any progression at six years. That’s right in line with what the radiation oncologist told me. (The nomogram is a little clunky to use, as it’s a graphical scale that you have to draw lines through to determine your score. I’d much rather have fields to enter on an online form that calculates it more precisely.)

There was one paragraph that talked about side effects of SRT that really caught my attention:

The potential for morbidity resulting from radiation therapy argues against its indiscriminate use in the salvage setting. Mild to moderate acute rectal and genitourinary toxicity is seen in the majority of patients, but the reported incidence of acute grade 3 to 4 complications is less than 4%.4,6,9,14,21,36 Late grade 1 to 2 rectal and genitourinary toxicity are reported in 5% to 20% of patients, and late grade 3 toxicity is less than 4%.3,4,6,8,11,21 Although rare, pelvic radiation therapy for prostate cancer is associated with an increased risk of secondary pelvic malignancies.40 Postprostatectomy radiotherapy does not appear to significantly increase the risk of urinary incontinence,3,4,6,14,21,41 but we must presume that it has some adverse effect on erectile function on the basis of the data from primary radiation therapy series. The nomogram can be used to restrict SRT to those patients most likely to benefit and avoid treatment-related morbidity in those predicted to have a low probability of a long-term benefit.

That 5% to 20% range for late grade 1 to 2 rectal and genitourinary toxicities made me go, “Hmmm…” Not quite the “single digits” probabilities that my radiation oncologist said.

After reading a number of the articles in the footnotes and listed on the “We recommend” column of the website, it’s apparent from most of them that starting SRT early is the way to go. It’s also apparent that the probability of being progression free at six years varies considerably from the 30% range to the 77% range depending on your PSA doubling time, PSA level, Gleason score, time to recurrence, and post-surgery pathology. But we already knew that.

This also caught my eye:

A rising PSA alone is not justification for initiating salvage therapy because patients with PSA recurrence are as likely to die as a result of competing causes as they are of prostate cancer.1 To determine the need for salvage therapy, we suggest using one of several existing tools to estimate the probability of developing metastatic disease or cancer-specific mortality.2,22,23 Patients at high risk of progression to these clinically significant events and/or a long life expectancy should be assessed for SRT using our nomogram.

Digging into the three footnotes listed, two are studies that I’ve already referred to in earlier posts—Pound and Freedland—and both suggest that it could take a very long time for the cancer to metastasize. The third study referenced, Predictors of Prostate Cancer–Specific Mortality After Radical Prostatectomy or Radiation Therapy, also reinforces that notion.

We’re right back where we started from: Zap early with an average 50-50 shot of it being effective (with the 4%-20% chance of long-term side effects) or do nothing but monitor.

I may send some of these links to my radiation oncologist on Tuesday and ask, “Which of these studies do you put the most stock in, and why?” and see what he says. Could be interesting.

Well that’s enough fun with cancer on a Saturday night. I’ll keep you posted on any new research findings or developments with the doctor.

Day 2,747 – Side Effects of Salvage Radiation Therapy

During my conversation with the radiation oncologist on Thursday, a big part of the discussion was on the long-term side effects of salvage radiation therapy. He stated that the probability of long-term urinary or rectal side effects was “in the single digits.” That reinforced my own understanding, but after the meeting, it occurred to me that we didn’t talk about the severity of those side effects in any detail.

I fired off an email to him on Friday asking, in essence, of those with long-term urinary and rectal side effects, what percent of those are mild, moderate, or severe?

He replied in a matter of hours and said that he couldn’t respond using the terminology in my email (I gave him definitions of what each of those meant in my own mind). Instead, he referred me to the Common Terminology Criteria for Adverse Events (CTCAE) used in standardizing terminology used in research across the globe. He referred me to “cystitis” and “proctitis” to see their definitions for grades 1 through 5. (Grade 1 was the least impactful; Grade 5 was typically death.)

The doctor also shared side effect data directly pulled from the manuscripts of 3 major randomized trials in post-prostatectomy patients. He didn’t provide the links—just the text—so I used the Google machine to come up with the links/articles. It’s interesting to note that all three are focused more on adjuvant radiation therapy than salvage therapy, but I suppose getting zapped for one is pretty much the same as getting zapped for the other.

 

Bolla et al, Lancet, Vol 366, Aug 2005

Late effects of rectal and bladder grade 3 or higher were only slightly increased in the XRT group vs. the observation group: 4.2% vs. 2.6%.

Wiegel et al, JCO, 2009

There was only one event of grade 3 toxicity (bladder). No grade 4 events were recorded. There were three events (2%) for grade 2 genitourinary adverse effects in the RT arm compared with none in the other arms. In addition, two grade 2 GI adverse effects (1.4%) were seen in the RT arm compared with none in the other arms.

It was interesting to note that the doctor omitted the second half of that paragraph from the original study:

Altogether, the cumulative rate of adverse effects for bladder and rectum (≥ grade 1) was 21.9% in the RT arm and 3.7% in the wait-and-see group (P < .0001; Appendix Fig A2, online only). One urethral stricture occurred in arm A and two occurred in arm B. Incontinence was not assessed, because it is not mentioned in the RTOG/EORTC scoring scheme.

Thompson et al, J Urology, 2009

We conducted a companion quality of life study in 217 men randomized to S8794 with assessments at baseline, 6 weeks, 6 months and annually for 5 years. A strength of this analysis was the inclusion of a 6-week assessment, designed to capture the side effects of radiotherapy at their peak. Tenderness and urgency of bowel movements were significantly more common at the 6-week point (47% vs 5%) in the radiotherapy group but by 2 years there was little difference between the groups. Urinary frequency was more commonly seen in the radiation group but there was no difference in the rate of erectile dysfunction (common in both groups) between groups. Global assessment of quality of life, while initially worse in the adjuvant radiotherapy group, became similar by year 2 and was increasingly superior in the radiotherapy group during the following 3 years. This gradual switch toward a superior quality of life in the adjuvant radiotherapy group should be examined in the context of the increased rates of PSA recurrence, salvage radiotherapy and hormonal therapy in the observation group, all of which have negative impacts on quality of life.

I’ve only skimmed the full studies at the moment, and I’ll come back to them in a day or two. On the surface, however, the numbers have eased my fear of long-term side effects a tad.

Right now, I just need to get away from the topic for a few hours and have some fun. Time to go out and play…

Stay tuned.

Day 2,745 – Conversation with the R.O.

When I was in 7th grade, I had to give a presentation on my science project, an erupting volcano, and I was so anxious about the presentation that I became physically ill and erupted myself. Not pretty. While I didn’t get physically ill today, the feeling was almost the same as I waited to see the radiation oncologist. It’s silly, I know. But it was very real.

In a nutshell, his recommendation was to start salvage radiation therapy.

The R.O. is a Navy captain medical officer, and we spent nearly forty-five minutes going over my case (which I truly appreciated). He took control of the conversation from the outset, explaining the options and consequences of each. I could tell that he had given this little presentation once or twice before. Once we got through that, we did have a real conversation. Some key points:

  • He disagreed with the notion that the increasing PSA is from residual benign prostate tissue left behind.
  • He was confident that the cancer would be in the prostate bed based on my numbers and statistics.
  • He talked about the differing definitions of biochemical recurrence, saying that the American Urological Association (AUA) and American Society for Radiation Oncology (ASTRO) use the 0.2 ng/ml threshold, but the National Comprehensive Cancer Network (NCCN) defines recurrence as a detectable PSA with two consecutive increases. My case meets the NCCN definition.
  • Continued surveillance is a viable option for me given my numbers and PSA doubling time.
  • We talked about the short and long-term side effects of radiation therapy: urinary control, sexual function and bowel control. His estimate the probability of long-term quality of life-impacting side effects in any of the three areas to be in the “single digits.”
  • He reminded me of selection bias when talking to other patients or bloggers about their side effect experiences. Yes, their experiences are very real, but for each person in an online forum, there are many others outside the forum who are leading productive, acceptable lives.
  • If we were to do salvage radiation therapy now with my PSA under 0.2 ng/ml, he put the probability of me having no evidence of disease five years from now at seventy-five percent. If we wait until my PSA is above 0.2 ng/ml, that number decreases.
  • Newer scanning technologies weren’t likely to pick up anything at my current PSA levels, yet he was open to the idea of them if it gave me peace of mind.
  • With my numbers, there is no reason to radiate the pelvic lymph nodes or use androgen deprivation therapy (ADT).
  • He was open to waiting until the August PSA results to see what they revealed before making a decision.

It was a good conversation, but I’m sorry to say that I don’t know that there was a lot of new information for me there that would tip the scale either way. The doctor wasn’t pushy in one direction or the other, saying that it was equally reasonable for me to continue surveillance or for me to begin salvage radiation therapy. The choice is mine. About the only thing he was adamant about was not starting ADT, and I’m in perfect agreement with him on that.

I did learn one really interesting thing, however. The reason that the VA Medical Center referred me to Naval Medical Center San Diego has to do with geology. Apparently VA Medical Center San Diego (La Jolla) was built sufficiently close to a geological fault line that they couldn’t build a radiation “bunker” that would be safe in the event of an earthquake.

What’s next for me? A ton of thinking, reflecting, and reevaluating.

Enough for now. I’m spent.

Day 2,717 – The Discussion

I hate this flippin’ disease.

My discussion with my urologist went pretty much exactly as I suspected it would, but with a few twists to screw with my mind a little. One of those little twists, however, happened much earlier than the meeting.

This morning as I was shaving, there was this strong sense of fear that hit me, tying my stomach in knots. That was completely unexpected and unfounded because I had a good idea of what was going to happen with the doctor. Even so, it was something that took control and definitely set my mood for the day.

When the doctor entered the exam room, I told him about my propensity to just verbally vomit all over the doctors before they even had a chance to explain their interpretation of my results. I shut up and let him talk away (with my battery of questions at the ready on my lap).

Pretty much everything that he said were things that I already knew:

  • The increasing PSA is a concern, but the slow rate of increase is a good thing.
  • That salvage radiotherapy would be the likely next step.
  • Given my pathology and history, it’s likely that the cancer is still in the prostate fossa.
  • Starting salvage radiotherapy earlier rather than later has typically shown to have better outcomes.
  • We have no guarantee of knowing where the cancer is at, so the radiotherapy may be ineffective.
  • Current imaging technologies aren’t good enough to detect the cancer’s location.
  • There’s no cut-and-dry set of numbers that would dictate specific actions.

The one kicker that knocked me for a loop was something that he said as we were reviewing my PSA tracking chart (I had to bring a copy of that, of course). He did mention the possibility that what we’re tracking may actually be benign prostatic tissue left behind that’s causing the PSA to rise. His reasoning was the fact that it took 54 months for the PSA to become detectable again and its slow rise ever since. He suspected that if the cancer was returning, the PSA would be climbing more rapidly. That, of course, would be great news. He didn’t assign a probability to his theory being right, however.

He did ask if I would be open to a referral to a radiation oncologist to at least begin the discussion and get educated. I said that, if he hadn’t suggested it, I was going to request it, so, yes, I was open to the referral. I don’t have an appointment on the calendar for that yet—they should call in the next few days.

I did mention the PSMA imaging trial that’s going on at UCLA and he was supportive of me looking into it. He cautioned, though that it is a trial and there’s no way to know yet how effective it may be. To be honest, it’s been a while since I looked at the trial page and I’m not sure that I would qualify to participate if it’s still ongoing. Something to dig into.

Lastly, he said there’s no need for urgent action at the moment. We’ll continue the four-month PSA test cycle for now. That will have me in the lab the first week of August.

When you get your care through the Veterans Administration (VA), as I do, you rarely see the same doctor twice. I mentioned that to this urologist and commented that, in a way, it’s a good thing because I’m getting multiple opinions and perspectives. He was taken aback by that comment, saying, “That’s a charitable view. I usually hear the opposite.”

He’s the second doctor who’s mentioned the possibility of this being nothing more than benign prostate tissue left behind that’s causing the PSA to return and rise. Perhaps I need to put a little more stock in that theory. But after spending two years wrapping my head around the notion that the cancer is returning—a mentally and emotionally exhausting exercise—when you hear something like this, it really screws with your mind. Or at least it does mine. It’s one more variable added to an ocean of uncertainty when you’re desperately seeking solid land.

The good thing is that I have time, and time may bring a little more clarity on which to base a decision at some point in the future. In the meantime, I’ll just don my kapok life preserver and bob around in that ocean of uncertainty reflecting on how much I hate this flippin’ disease. (Yes, I’m dating myself with the kapok reference.)

 

 

Month 87 – Adapting and Researching

Ever since my December meeting with my doctor to review the latest uptick in my PSA reading to 0.10 ng/ml where he told me I need to begin to think about salvage radiation therapy, it’s as though the clock has been turned back to when I was first diagnosed. That makes this all very real once again. We’re getting closer to having to make a decision to move from monitoring to action.

My emotions have been all over the place—from mad as hell at the world to ready to bawl at the drop of a hat—and I felt compelled to research as much as I could, as fast as I could even though my next PSA and doctor’s appointments aren’t until April. On the good news front, the peaks and valleys on the emotional roller coaster have diminished some over the last two months. They’re still there, but not as bad as they initially were.

IMG_4828
San Diego at Night

I’ve been spending a good amount of time (perhaps too much) researching and hanging out in the advanced prostate cancer section of various online support groups. That’s been both helpful and a tad frightening. It’s been helpful because I’m new(er) to the advanced prostate cancer discussion, and I’ve been learning more about the different treatment options, protocols, and latest research. It’s been frightening because reading the first-hand stories—while valuable and necessary—has stoked my fears of the treatment side effects.

I did come across one thing in my research that I’ll definitely discuss with my doctor in April.

We know biochemical recurrence after prostatectomy has been widely defined at 0.2 ng/ml for quite some time, yet more and more research is indicating that salvage therapy should begin early in order to have the best chance of success. Some suggest starting SRT before hitting the 0.2 ng/ml threshold.

Of course, as we all know in the field of prostate cancer, nothing is clear-cut. You can easily find research that has conflicting recommendations.

I came across Stephen J. Freedland’s 2005 study (co-authored by Alan Partin and Patrick Walsh—heavy hitters in the prostate cancer world from Johns Hopkins) that shows I may not have to do anything other than continue to be monitored given my status (PSA = 7, PSADT > 15 months, time to recurrence > 3 years). In fact, he writes:

“It is amazing to me that for a man who has all the low-risk features – if his PSA doubling time is greater than 15 months, his Gleason score is below 8, his PSA comes back after three years – his odds of being alive 15 years later are 94 percent.” These men do not need treatment, he adds. “If we know that 94 percent of these men are alive and well 15 years after surgery with no further treatment, anything we do to treat them is unlikely to improve on that, and probably would only affect the quality of life.”

That’s quite encouraging for someone fearful of side effects and loss of quality of life. Combine that with the Pound study done in 1999 that said it takes on average eight years to metastasis after BCR and, on average, another five years to death after metastasis without any additional treatment, and you’re building a stronger case for doing nothing other than continued monitoring for those of us who are averse to treatment side effects. At least in my mind at the moment.

You can read an abbreviated summary of the Freedland study in the Johns Hopkins newsletter, Prostate Cancer Discovery, here, and the full study as published in JAMA here.

I’m slowly adapting to this new path that I’m on, and I’ll work to find the right balance to stay away from the online support groups and the Google machine to maintain a sense of sanity. I fear, however, that controlling the emotional roller coaster is going to be far more challenging from this point forward (steer clear or pass the tissues). Just a hunch.


One related footnote. I’ve not yet met with a radiation oncologist since my PSA started going up in September 2015. If it stays the same or goes up again in April, I’ll ask the urologist for the referral just to start the conversation and learn more from his/her perspective.