Long-Term Adverse Effects and Complications After Prostate Cancer Treatment - JAMA Oncology, Nov 7, 2024 - w/ SWOG commentary

[cujoe]

A very important baseline study for those considering treatment options. This paper would have been very useful for a very good friend of mine who treated with Cyberknife RT several years back. He had severe radiation cystitis following the RT (which failed to improve with hyberbaric treatments), and has had to resort to the use of a permanent retropubic catheter to control his cistitis-related incontinence. As was the case with my friend, the paper suggests that you should be very thorough in examining both the best options for your particular situation AND in finding a very competent doctor to oversee its implementation. Be sure to also read the entire SWOG article linked below.

* * *

Long-Term Adverse Effects and Complications After Prostate Cancer Treatment, Original Investigation,November 7, 2024:

Joseph M. Unger, PhD1; Cathee Till, MS1; Catherine M. Tangen, DrPH1; et al Dawn L. Hershman, MD2; Phyllis J. Goodman, MS1; Michael LeBlanc, PhD1; William E. Barlow, PhD1; Riha Vaidya, PhD1; Lori M. Minasian, MD3; Howard L. Parnes, MD3; Ian M. Thompson Jr, MD4

JAMA Oncol. Published online November 7, 2024.

doi:10.1001/jamaoncol.2024.4397

* * *

Key Points

Question What long-term complications of treatment for prostate cancer (PCA) are experienced by treated patients compared with a general population of older males?

Findings This cohort study, including 3946 patients with PCA, used a novel data linkage between 2 large PCA prevention clinical trials and Medicare claims to determine PCA treatment was associated with substantially higher rates of complications 12 years after treatment. Moreover, participants treated with radiotherapy had a 3-fold increased risk of bladder cancer and a 100-fold increased risk of radiation cystitis and radiation proctitis.

Meaning After accounting for age-related symptoms and diseases, PCA treatment was significantly associated with higher rates of complications 12 years after treatment, a finding that highlights the importance of patient counseling and provides a rationale for pursuing opportunities for cancer prevention.

Abstract

Importance Due to the often indolent nature of prostate cancer (PCA), treatment decisions must weigh the risks and benefits of cancer control with those of treatment-associated morbidities.

Objective To characterize long-term treatment-related adverse effects and complications in patients treated for PCA compared to a general population of older males.

Design, Setting, and Participants This cohort study used a novel approach linking data from 2 large PCA prevention clinical trials (the Prostate Cancer Prevention Trial and the Selenium and Vitamin-E Cancer Prevention Trial) with Medicare claims records. This analysis included patients with PCA who had been treated with prostatectomy or radiotherapy compared with an untreated control group. Multivariable Cox regression was used, with a time-varying covariate for the occurrence of PCA treatment, adjusted for age, race, and year of time-at-risk initiation, and stratified by study and intervention arm. Data analyses were performed from September 21, 2022, to March 18, 2024.

Exposure Prostatectomy and radiotherapy occurring after a PCA diagnosis, identified from trial data or Medicare claims records.

Main Outcomes and Measures Ten potential PCA treatment-related complications identified from Medicare claims data.

Results The study sample comprised 29 196 participants (mean [SD] age at time-at-risk initiation, 68.7 [4.8] years). Of these, 3946 participants had PCA, among whom 655 were treated with prostatectomy and 1056 with radiotherapy. The 12-year hazard risk of urinary or sexual complications was 7.23 times greater for those with prostatectomy (95% CI, 5.96-8.78; P < .001) and 2.76 times greater for radiotherapy (95% CI, 2.26-3.37; P < .001) compared to untreated participants. Moreover, among participants treated with radiotherapy, there was a nearly 3-fold greater hazard risk of bladder cancer than in the untreated (hazard ratio [HR], 2.78; 95% CI, 1.92-4.02; P < .001), as well as an approximately 100-fold increased hazard risk of radiation-specific outcomes including radiation cystitis (HR, 131.47; 95% CI, 52.48-329.35; P < .001) and radiation proctitis (HR, 87.91; 95% CI, 48.12-160.61; P < .001). The incidence per 1000 person-years of any 1 of the 10 treatment-related complications was 124.26 for prostatectomy, 62.15 for radiotherapy, and 23.61 for untreated participants.

Conclusions and Relevance This cohort study found that, even after accounting for age-related symptoms and disease, PCA treatment was associated with higher rates of complications in the 12 years after treatment. Given the uncertain benefit of PCA treatment for most patients, these findings highlight the importance of patient counseling before PCA screening and treatment and provide a rationale for pursuing opportunities for cancer prevention.

* * *

The comment from SWOG summary of the paper (linked below) summarizes the impact these findings should have on treatment decisions:

* * *

The report – by researchers from the SWOG Cancer Research Network, a clinical trials group funded by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), along with researchers from the NCI – argues that men need to have access to risk numbers such as these when deciding whether to even be screened for prostate cancer.

“This study throws down a major gauntlet to all physicians to give patients this information before they even begin the process of drawing a PSA test,” said the paper’s senior author Ian M. Thompson, Jr., MD, of CHRISTUS Santa Rosa Health System and The University of Texas Health Science Center at San Antonio. A PSA test measures the blood level of a protein called prostate-specific antigen.

* * *

The paper abstract can be found here, but the entire paper is behind a paywall:

Long-Term Adverse Effects and Complications After Prostate Cancer Treatment, Original Investigation,November 7, 2024:

jamanetwork.com/journals/ja...

and the full SWOG commentary is here:

Long-Term Risks from Prostate Cancer Treatment Detailed in New Report , SWOG Communications Manager, November 7, 2024

swog.org/news-events/news/2...

* * *

Thinking (long and hard) before you treat would seem to be the take-home message for both you and your doctor(s).

Stay S&W,

Ciao - cujoe

[NPfisherman]

Dog of Terror:

Thanks for posting....

It is the struggle that "newbies" face as to what is the best option for them in seeking treatment...

The issue for some, of course, will be how do I balance all the factors?? I think that looking at biopsy results is part of what goes on the scale, but age... other issues ...can complicate finding a course forward...

I kind of wish they looked at SBRT in regards to avoiding some of the radiation issues... Ultimately, the older members can look at these numbers and how they fit into their own course...

DD

[cujoe in reply to NPfisherman]

DD, Absent access to the full article, it a bit unclear what forms of RT they examined.

My friend profiled in the post had somehow determined that Cyberknife, specifically, was the best treatment for his state of disease. However, I'm now convinced that his decision was mostly made based on the convenience of the treatment center to his home. That he continued with the planned treatment team even after a botched first run at the procedure to place the target fiducials and protective gel-pack came as a major shock to me.

As soon as he told me of the screw-up, I got him the name of a well-regarded oncologist at one of the country's best cancer centers (about an hour drive from his home) for a second opinion review before going forward, but he did not use it. After the hyperbaric sessions did not improve the bladder cistitis, he said that he "should have had surgery". The bright spot (so far) is that his PSA is has remained "undetectable" since the RT.

IMO, his case is a perfect one that illustrates the need to be super-diligent when making any and all major healthcare decisions. Second (and third) opinions should never be discouraged by a well-trained, expert doctor. In fact, they should be encouraged for potentially life-altering procedures - and initial PCa treatments definitely qualify in that regard.

Hope all is well in your world. Ciao - K9

PS BTW, in his usual insightful humor, it was j-o-h-n who gave me the "sometimes K9 terror" moniker in a post reply not long after I joined HU

[GreenStreet]

Thanks for posting. Super interesting and super important because there is no such thing as a free lunch and we have to make trade offs often with imperfect data but we owe it to ourselves and our partners/families to be as informed as possible. Totally agree re second opinions and some are very touchy about it. Long term implications are interesting. In my case I had CyberKnife spot treatment 3 years ago to a lymph node that was 2 ml from my bowel. I was very reassured that I faced a delay on the day that my gold marker was placed in that the experienced consultant had been delayed and the one on hand refused to do it because he did not think he was experienced enough. That takes some courage to admit and an excellent safety culture for the conversation to have taken place. I was obviously happy to wait all day or even all week for the right person. 3 years later the trade off is very satisfactory but I take the point that side effects of radiation emerge over time.

[cujoe in reply to GreenStreet]

GreenSt - In the case of my friend, he was on the table for the fiducial procedure and the doc said ~ "Hey, where is the rest . . ."; i.e., they had only receive one of 2 FedEx packages needed to do the procedure. When told that story, I strongly suggested to him that he call the contact at the major cancer center an hour away and beg him for an emergency review consultation! Of course, as I said earlier, that never happened and he continued with the same treatment team that had already demonstrated some degree of poor practice management that could be said to border on professional incompetency.

Your experience is the one an informed, self-advocating patient usually hopes (and expects) to make happen. I learned that the hard way by not seeking a second opinion (and biopsy review) after my first needle biopsy. Had I done that, I expect I would have been treated earlier while the cancer was organ-confined. In addition to being a "sometimes K9 terror", Moi can also be a "sometimes slow learner" for sure. I am now extremely fortunate to still be living and breathing with a fine QOL some 12 years after my RALP - and in spite of having metastatic disease.

Part of our mission here is to pass on our experiences to others, so they can improve on ours as needed. Many thanks to you and the others who so generously share your journey to make that possible.

Keep Safe & Stay Well, Ciao - cujoe

[GreenStreet]

Wow that was disappointing and pretty unprofessional. I think when you have been treated well as I was on that day by every single member of staff that it is important to provide appreciative feedback to reinforce positive behaviour and I did that by writing a personal letter to the medical director commending the staff. I also make sure that I talk to the team working all the machines and take an interest. They work in difficult conditions with no natural light. Like you in my early days I was not well informed and did not realise that the strength of the MRI machine at my local hospital was only borderline acceptable and did not pick up that my cancer was not confined to the prostate. I had surgery rather than radiotherapy. Fortunately I am now at the Royal Marsden where they have good machines. I consider myself lucky in that I am still here nearly 10 years on. Best wishes and Good luck to you too,

[Slowdancing]

First of all, that was just a retrospective (observational) study, with all of the drawbacks they come with. Secondly, it's misleading to state that there were "xxx times more y" when the baseline numbers for y are so small to begin with.

An actual very well run randomized controlled study was recently released, which showed that at least at the 5 year point, side-effects from prostate radiation therapy (both SBRT and IMRT) were very low. (as well as very high 5 year effectiveness for both).

No current therapy is side-effect free, but in order to choose intelligently, the best available information regarding the current state of the art procedures should be taken into account.

nejm.org/doi/full/10.1056/N...

"We previously found a significant difference in the incidence grade 2 or higher genitourinary toxic effects at 2 years after treatment (12% with SBRT vs. 7% with control radiotherapy). The updated 5-year toxicity analysis indicates a decrease in the incidence of these symptoms, with no significant differences between the two groups at 5 years, and low overall levels of side effects."

[cujoe in reply to Slowdancing]

SD - Apples to oranges comparison - with the RCT focused only on SBRT for localized disease and the observational study looking at a broad comparison of treatment outcomes across a large population. The NEJM CT is a good one for anyone considering SBRT as a treatment choice, whereas the JAMA/SWOG is focused on the overall risks for various treatments as compared to men who are not treated over a much longer period of time.

From the SWOG summary report:

* * *

One challenge in determining the risk of adverse effects from prostate cancer treatment is that for some of these conditions, such as erectile dysfunction, the incidence increases with age. So, a true measure of risk can be determined only by comparing men treated for prostate cancer with untreated men of similar age in the general population. The JAMA Oncology study does just that.

“Past studies of prostate cancer treatment complications have had small sample sizes, limited follow up, or the absence of a valid control group,” said lead author Joseph Unger, PhD. “Our study is distinguished by long follow-up, out to 12 years, looking at a broad spectrum of key complications. Critically, we were able to compare treated men to a representative control group of untreated men, which prior studies have not included.”

The issue of comparing to a valid control group is key, Dr. Unger noted: “Without this, it is difficult to understand the true magnitude of treatment complications.”

* * *

It's a matter of using the right "tools" to make an informed decision at an appropriate time; i.e., both papers provide guidance for men making critical decisions that will more than likely affect their long and short-term QOL, not to mention their lifespan.

Thanks for the comment and for posting the RCT link. Stay S&W,

Ciao - cujoe

[dhccpa]

Excellent. Unfortunately, a large majority of docs will never read it, hear about it, or change what they're doing now. I know that's a cynical view, but I think it's realistic. Patients can try to bring it up.

[cujoe in reply to dhccpa]

dhccpa - That's why we put such info out here on the patient forums - so patients can be informed enough to "bring it up" with their docs. The challenge for most is being informed BEFORE we are asked to make the critical (and irreversible) treatment decisions that will chart the rest of our lives. Patients aren't often initially informed until after they are challenged to make such decisions. Ignorance may be bliss until it permanently affects your QOL.

Keep a positive mindset and stay S&W.

[dhccpa in reply to cujoe]

You're exactly right.

[Break60 in reply to cujoe]

If we were told how bad things could get in the future wouldn’t we still choose to do what’s necessary to kill the beast and cross the other bridges when we need to? There are no easy ways to deal with this disease. At least it’s not the worst type of cancer.

[Break60]

I certainly agree with these findings! Eleven years after RP and SRT I’m totally incontinent and have had multiple UTIs requiring hospitalization . I’ve been wearing briefs and pads for many years and a Foley catheter for the last couple of years. But I’m alive so I guess the treatments were worth it. No free lunch!

[cujoe in reply to Break60]

Break - I see from your profile that you had the AUS, but had to have it removed about a year later due to sepsis, serial UTIs, and functional urinary tract issues. As I dealt with serious incontinence for about 3 years after RALP + IMRT before having my first AUS surgery, plus for 6 months between the failure of #1 and surgery to replace it w/ #2, I know well the impacts that incontinence and pad-use has on one's QOL. However all knowledge I have of the multiple urinary issues and long-term catherter use you are currently experiencing is all second-hand. And while 'free lunches" may be rare, it would seem you are overdue for one. I sincerely hope things improve for you.

Be Well, Ciao - cujoe

[Break60 in reply to cujoe]

Thanks . I’ve gotten used to the pads and foleys . It’s amazing the conditions you learn to deal with. I see the war fighters who came back with PTSD and missing limbs and count my blessings.