Second primary malignancies

New study from Taiwan, below [1].

Of interest, since the findings are somewhat different from past U.S. studies.

However, I recognize that the subject is a downer. After all, who wants to contemplate dealing with a second cancer? Some might want to skip this post. On the other hand, some will want to understand the risk. & note that if a small risk doubles, it remains a small risk.

When I had salvage radiation over 12 years ago, I was told that my chance of colon cancer would rise after 5 years. After 10 years, I reluctantly had a colonoscopy (unrelated to PCa). The pictures were reassuring - the tissue looked very healthy: remarkably so, I felt. And it occurred to me that many of the supplements I use might help prevent colon cancer. & perhaps other cancers. & might even slow the progress of occult cancer. Maybe I will be unlucky, but I feel that I am doing something to level the playing field.

Perhaps addressing chronic sub-clinical inflammation is the answer (which has been one of my targets). See my series of posts on inflammation.

Taiwanese "Men with PCa had a trend of lower risk of developing overall SPMs {second primary malignancies} compared to those without PCa ..." 5% less!

Based on a population of 30,964 men with PCa, diagnosed between 2000 & 2011. Controls: "frequency-matched with an individual without PCa, based on age, comorbidity, and index year"

I don't know how much screening goes on in low-risk Taiwan, but in a country without any screening, all cases would be advanced at diagnosis & mortality would be grim. Little time for a second cancer to be identified. In an over-screened population such as the U.S., with prompt treatment, survival statistics would be very good, with perhaps ample time for a 2nd malignancy to be diagnosed. {The U.S. PCa "10-year relative survival rate is 99.7%" [4] Thanks largely to all the Gleason 3+3 cases.}

So men with PCa in Taiwan get fewer secondary cancers. However: "In contrast, these patients had a significantly higher risk of thyroid cancer" than men without PCa. Adjusted sub-hazard ratio = 4.62.

The PCa-thyroid connection is something I have discussed before. Some studies support it, but there is a paper [5] that suggests that both cancers are over-diagnosed (and over-treated) & that men who have both are probably over-screeners (blame the victim). After all, what possible connection could there be?

For me, the connection might be iodine deficiency. I became aware of the possible importance of iodine in the prostate 12 years ago & started using it. Prior to this, I had visited a hand surgeon who diagnosed a painful trigger finger as being caused by Dupuytren's contracture. He offered no treatment - or rather, advised against surgery, which is rarely helpful.

The diagnosis & the start of iodine use was one of those serendipitous timings that sometimes occur. The overgrowth of connective tissue in my palm disappeared at about the same rate as it had grown (it had been growing pretty fast, so was almost all gone in 12 months.)

The iodine deficiency / PCa & Dupuytren's connections are mentioned in Dr. Brownstein's "Iodine: Why You Need It, Why You Can't Live Without It", but are rarely discussed elsewhere.

Anyway, if the Taiwanese are not over-screening, the PCa-thyroid cancer statistic might not be a screening anomaly after all.

Dr. Myers ruefully refers to radiation as "the treatment that keeps on giving." My urologist, speaking of bladder issues in PCa cases, told me that he spent a lot of time "cleaning up" after radiologists. (Are oncologists even aware of such problems? Or patients?)

"Further analyses indicated that PCa patients who received radiation therapy (RT) had an increased risk of overall SPMs, hematologic malignancies, esophageal cancer, liver cancer, lung cancer, and urinary bladder cancer compared with those who did not receive RT."

Why? Many men who could opt for surgery are persuaded that radiation is better, but older men with serious comorbidities usually don't have the option of surgery. The Taiwan finding might reflect that - although "urinary bladder cancer" may be due to radiation, of course.

[2] (2016 - U.S.) "Risk of second primary malignancies among cancer survivors in the United States, 1992 through 2008." (not PCa-specific)

"A cohort of 2,116,163 patients was identified, 170,865 of whom (8.1%) developed a second primary malignancy."

Thankfully, no special mention of PCa in the Abstract, but the full text would have the PCa details.

[3] (2013 - U.S.) Does ADT affect risk?

"Our results suggest that among men with localized prostate cancer, ADT is not associated with an increased risk of second primary malignancies."

[4] (2014 - U.S.)

"A population-based cohort of 441,504 men who were diagnosed with prostate cancer between 1992 and 2010 was identified ..."

"The risks of leukemia and cancers of the oral cavity and pharynx, esophagus, stomach, colon and rectum, liver, gallbladder, pancreas, lung and bronchus, and larynx were significantly lower."

"Conversely, these patients had a greater risk of bladder, kidney, and endocrine and soft tissue cancers."

"Men who received treatment with radiation therapy (external-beam radiation therapy) had long-term increases in their risk of bladder cancer (SIR = 1.42) and rectal cancer (SIR = 1.70) risk compared with who did not receive radiation ..."

"Men with early onset prostate cancer had a ... higher risk of ... thyroid cancer (SIR = 1.63 ...) compared with men in the general population and in contrast to men who were diagnosed at older ages (... thyroid cancer, SIR = 1.02 ...)"

"Overall, we observed that prostate cancer survivors had a 40% lower risk of developing a second primary cancer compared with the general US male population. Specifically, they had a lower risk of developing leukemia and cancers of the oral cavity and pharynx, esophagus, stomach, colon and rectum, liver, gallbladder, pancreas, lung and bronchus, and larynx."

[5] PCa & Thyroid Cancer.

[5a] (2015 - U.S.)

"Prostate and thyroid cancers represent two of the most overdiagnosed tumors in the U.S. Hypothesizing that patients diagnosed with one of these malignancies were more likely to be diagnosed with the other, we examined the coupling of diagnoses of prostate and thyroid cancer in a large U.S. administrative dataset."

"There is a significant association of diagnoses with prostate and thyroid cancer in the U.S. In the absence of a known biological link between these tumors, these data suggest that diagnosis patterns for prostate and thyroid malignancies are linked."

[5b] (2014 - Zurich, Switzerland)

"When stratified by treatment, the highest {standardized incidence ratio} was observed for thyroid cancer (3.57 ...)" (in PCa cases)

[5c] (2005 - U.S.) Here is an interesting PCa-thyroid connection. It relates to thyroid- stimulating hormone (TSH).

"The effect of Gleason score on TSH level was significant ... and independent of the effect of age ..."

"We propose that the high serum TSH levels in men with Gleason 8 prostate cancer is a result of the elaboration of TSH by cancer cells. Bone mineral density in the face of normal levels of thyroid hormone depends on an intact response to TSH, which ordinarily suppresses both osteoblast and osteoclast differentiation, thereby exerting control over bone remodelling. However, with abnormally high TSH levels this process may become deranged, promoting the development of bone metastases. If TSH production by prostate cancer cells could be suppressed, the incidence of bone metastases might be reduced."

-Patrick

[1] journals.plos.org/plosone/a...

[2] ncbi.nlm.nih.gov/pubmed/273...

[3] ncbi.nlm.nih.gov/pubmed/232...

[4] ncbi.nlm.nih.gov/pmc/articl...

[5a] ncbi.nlm.nih.gov/pmc/articl...

[5b] ncbi.nlm.nih.gov/pubmed/250...

[5c] ncbi.nlm.nih.gov/pubmed/160...

13 Replies

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  • Had colorectal in 2002 followed by PCA in 2008. Just lucky I guess.

  • I've had four unrelated primary cancers, and no significant radiation. None of my doctors, including several oncologists, suspect any connection simply because they are all of different medical origin ... different pathways (especially the self-induced basal cell carcinoma on my shoulder after a lifetime in the sun. "$#!+ happens" is their best explanation. I HOPE to live long enough for my pre-ADT, gynecomastia-prophylactic, 12 gy of chest irradiation to give me breast cancer.

  • How'd you swing that chest irradiation? I mentioned that to two urologists as something I'd be interested in ... and they both scoffed at the idea. Ha, ha, ha.

  • One of the most common SEs of ADT, and one of the most common reasons men quit ADT, is the combination of gynecomastia (breast growth) and the severe mastalgia (breast pain) that accompanies it. Once they occur, they are permanent. Pre-ADT prophylactic pecs irradiation has been shown in multiple studies to prevent or reduce them in a large minority of men on ADT, has no downside, takes a few minutes, is strongly advised by almost every PC book I've read, and is part of Leibowitz's protocol. It's a no-brainer to me, considering the alternatives: boobs, pain, and/or tamoxifen. The latter works better than irradiation (if we're to trust ANY drug studies any more), but has some fairly life-threatening SEs such as DVT.

    I don't take my car's computer problems to my gardener, my bark beetle infestation to my car dealer, or my PC to my urologist, and I check my RV tire pressures before long trips, not after they blow out at 70 mph.

    Every one of these doctors works for us, not the other way around. I will defer to SOME of them on cellular biochemistry issues beyond my ken (e.g., only Leibowitz had even a chance at talking me into early chemotherapy, and only into his protocol), and we're taking it one unnoticeable infusion at a time.

    Some of my oncologists scoffed at prophylactic chest irradiation, too, or at the very most said I could get it if I wanted to. But then WTH do they care ... they leave SEs up to our PCPs and don't see the aftermath. I don't "swing"; I insist if necessary, just like I informed Leibowitz multiple times and ways that the minute I get near disabling neuropathy, we're done. That changed some of my meds against his wishes, but this is my life, not his. I apparently don't enjoy irreversible and intractable 24/7 pain, wheelchairs, and sleep deprivation as much as some men seem to.

    BTW, he also insists that G 3+4=7 PC behaves like G6 ... i.e., seldom warrants anything beyond active surveillance. If he's right, just think of all the SEs men have suffered for no reason over the decades and across the globe.

  • All excellent points. It is easy to be thrown for a loop by your diagnosis and be in a state where you just defer to the 'experts'. You really do have to stand up and insist on good care. The cavalier attitude of urologists and oncologists to SE's is shameful.

  • Patrick,

    I almost didn't read this, but since it was you ...

    Thanks to an earlier email exchange with you about fluoride, I take Iodoral & Potassium Plus Iodine.

    With a Gleason of 3 + 4, would you be worried enough about your TSH level to look into having it tested? Is there any way to suppress TSH production by PCa cells? Thank you.

    Neal

  • Neal,

    I tend to use specific LEF blood tests to monitor what interests me (sale now on), but they have a cheap "kitchen sink" panel that I like, which has TSH.

    In 2015, my TSH was 1.090 uIU/mL (ref: 0.450-4.500). (0.531 in 2013)

    (my GS was 4+3 at diagnosis)

    I think it's worth having a full panel every 2 years of so. Turns out that the basic panel has a number of test items that are more important than I suspected a dozen years ago.

    Here is something on elevated TSH:

    todaysgeriatricmedicine.com...

    -Patrick

  • Thank you very much, Patrick. This is very helpful. I'll share the article with my PCP.

  • Patrick, I have been on Thyroid replacement Medication for about 5 years. So my levels are being artificially addressed. I had a post about trigger finger. You did not respond. I have found many men who responded, and all were on ADT or most were on ADT and Metformin.

    Did Iodine supplementation cure your Trigger Finger? Were you on Metformin at the time?

    In my case finger stiffness and Trigger Finger led to me finding out how much inflammation I might have, which led to a C-reactive protein test, which came back zero---GP, Donaldson, and Oncologist, said they never saw a zero. X-rays, showed hands to be perfect, no arthritis.

    So I am trying to figure this out. As respondents to my post as I said all had one thing in common, ADT[2 minimum], but most have or had a course of ADT+Metformin.

    Any ideas.

    Nalakrats

  • Nalakrats,

    Dupuytren's was 12 years ago - at least 5 years before I began Metformin. & I was on long-term androstenedione (later T) at the time. No ADT.

    -Patrick

  • Interesting, I have responses from over 20 men with trigger finger and finger stiffness. None of my Docs. have the slightest bit of an answer. Alan Meyers, had the same--he cured it with extreme hand exercise--using grippers, and squeezers, to generate hand and finger strength. This is a side affect for some, that is one for the books--so far.

    Nalakrats

  • Nalakrats,

    A Dupuytren's trigger finger is preceded by an overgrowth of connective tissue in the palm. See the picture in:

    en.wikipedia.org/wiki/Dupuy...

    Hard to believe it can be reversed. All I am left with is a tiny dip in a lifeline. I can feel no overgrowth at all.

    It is often called the Viking disease, as though there is a genetic cause, but iodine deficiency was the primary cause of mine.

    Peyronie's curvature of the penis is related. 15-20 years ago, Johns Hopkins noted that RP patients would sometimes complain of it. JH couldn't figure out how the surgery could do that.

    Of course, surgery shortens the urethra, & there is a pulling sensation on the penis for some months - but permanent curvature? Too bad they didn't check iodine status.

    -Patrick

  • Thanks Patrick, as always!

    Nalakrats.

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