Hormone treatment side effects

John M · Experienced user Joined: 27 Jul 2009 Posts: 59

I did a search on these two authors on Pubmed, and cannot find any articles by them on brachytherapy. What studies are you talking about when you say,

"I can point to studies by Datoli and Blasco that show the opposite.
Urinary irration occurs after Brachytherapy, but you use FlowMax and it becomes very managable in fact unnoticable after a few weeks; total urinary obstruction is rare. "

Pubmed is the free service provided by the NIH (http://www.ncbi.nlm.nih.gov/sites/entrez) which allows one to search the entire world's medical literature that is published in peer-reviewed journals.

The article that I posted does show that brachytherapy has fewer sexual and urinary complaints overall than surgery at 24 months, but more complaint about urinary obstruction, and a lot more bowel complaints. This is a really large and careful study. The main limitation is the limited followup. Some of the complications of radiation and brachytherapy may increase over time, and those of surgery may decrease. BTW, this entire article can be downloaded for free at the link I listed above, so if you want to discuss the actual evidence, you can do it.

This is a complicated issue. There are advantages and disadvantages for each treatment, and different treatments are best for different people. Who knows who reads these posts and how it may affect people's decisions? If we give advice, we should try to be accurate and check it out carefully.
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John

JerryB · Regular Joined: 13 Jul 2009 Posts: 43 Location: UK

The fact that my consultant surgeon told me that I might not be a suitable candidate for brachytherapy because of my BPH tends to reinforce some comments I have read elsewhere. Namely, if one already has problems of flow, these are likely to be exacerbated, certainly for a few months and possibly for longer, by brachytherapy. Which is not to say that brachytherapy overall is not an excellent procedure; just that in my case, it may not be the best procedure.

I find it very interesting reading the intelligent and informed discussions in this thread and other threads, often based on evidence obtained elsewhere, that there is obviously so much conflicting 'professional', 'trialed', and 'reliable' information available on various protocols, diagnoses and treatments options. Even the 'experts' frequently don't seem to be able to agree among themselves. Is this something specific to prostate cancer because of its complexity in diagnosis and treatment, or maybe it just happens generally within the medical profession?

I mentioned that I am looking into other options, and at the moment I am leaning strongly towards HIFU. No decisions yet, because it hasn't been determined whether I am a suitable candidate, but for me (and I emphasise, for me) it appears to be worth seriously considering. Admittedly, the period of suprapubic catheterisation and possible problems of blockages while the ablated tissue is rejected is a factor to be taken into account, but the results now being obtained by one of the top guys in the UK seem to be quite impressive.

I am currently awaiting the results from a procedure called Prostate Mapping which claims to give approximately 95% accurate indication of cancer spread, burden and aggressiveness. I decided to go for this because the TRUS biopsy provided under the NHS in the UK, while better than nothing, certainly cannot claim to be highly accurate. I need to know as reliably as possible where my cancer is and how much of it there is, to be able to make informed decisions about where to go from here.

Once I have the information from the Prostate Mapping I shall probably post again here when I have decided which treatment to go for.

Cheers,

Jeremy

John M · Experienced user Joined: 27 Jul 2009 Posts: 59

Here is the summary assessment on current evidence on HIFU from the European Association of Urology 2009 Prostate Cancer Guidelines (http://www.uroweb.org/nc/professional-resources/guidelines/online/):

11.3 High-intensity focused ultrasound (HIFU)
HIFU consists of focused ultrasound waves emitted from a transducer to cause tissue damage by mechanical and thermal effects as well as by cavitation (15). The goal of HIFU is to heat malignant tissues above 65 °C in order to destroy them by coagulative necrosis. HIFU is performed under general or spinal anesthesia, with the patient in the lateral (Ablatherm®) or supine (Sonablate® 500) position; the procedure is time-consuming, with about 10 g prostate tissue being treated in one hour. In a recent review, 150 papers related to HIFU were identified and evaluated with regard to various oncological and functional outcome parameters (12). No controlled trial was available for analysis, and no survival data were presented. No validated biochemical, surrogate end-point was available for HIFU therapy.

11.3.1 Results of HIFU in PCa
As with CSAP (Cryosurgery of the prostate), it appears to be difficult to interpret oncological outcome in patients undergoing HIFU since various PSA thresholds are defined and no international consensus exists on objective response criteria. The results of HIFU are limited, with outcome data from fewer than 1000 PCa cases having been published in the literature. According to the recent review paper mentioned above (12), HIFU showed progression-free survival (based on PSA +/- biopsy data) of 63-87% (projected three- to five-year data), but median follow-up in the studies ranged from 12-24 months only. In one of the largest single-centre studies, 227 patients with clinically organ confined PCa were treated with HIFU and their outcome data were analysed after a mean follow-up of 27 months (range = 12-121 months) (16). The projected five-year biochemical disease-free survival was 66%, and or only 57% if patients had exhibited a pre-therapeutic PSA value of 4-10 ng/mL. Incontinence and bladder neck stricture decreased over time from 28% and 31% to 9% and 6%, respectively. In one of the studies (17), a significant decrease in pre-treatment PSA serum levels from 12 ng/mL to 2.4 ng/mL was observed. However, 50% of the 14 patients demonstrated positive prostate biopsies during follow-up. In another study (18), a complete response rate defined by PSA < 4 ng/mL and six negative biopsies was achieved in 56% of the patients. Summarising the efficacy results of a European multicentre study comprising the data of 559 patients with mainly low- and intermediate-risk PCa, Thüroff et al. (18) reported on a negative biopsy rate of 87.2% in 288 men with a follow-up of at least six months. A PSA nadir after six months follow-up could be determined in 212 patients, and it was as high as 1.8 ng/mL. However, it could be demonstrated that the PSA nadir might be reached at 12-18 months following the initial procedure. Blana et al. reported on 146 patients undergoing HIFU with a mean follow-up of 22.5 months (19). The mean PSA level at initiation of therapy was 7.6 ng/mL; the PSA nadir achieved after three months was 0.07 ng/mL. However, after 22 months the median PSA level was 0.15 ng/mL. Of the 137 men available for analysis, 93.4% demonstrated a negative control biopsy. The PSA nadir appears to be strongly associated with treatment failure (20) (p < 0.001). Patients with a PSA nadir of 0.0-0.2 ng/mL have a treatment failure rate of only 11%, compared with 46% in patients with a PSA nadir of 0.21-1.00 ng/mL, and 48% with a PSA nadir of >1.0 ng/mL. Recently, the group updated its results, with a total of 163 men treated for clinically organ-confined PCa. Within 72 Update march 2009 the 4.8 +/- 1.2 years of follow-up, the actuarial disease-free survival rate at five years was 66%, with salvage treatment initiated for 12% of the patients (21).

11.3.2 Complications of HIFU
Urinary retention appears to be one of the most common side-effects of HIFU, developing in almost all patients, with the mean interval of catheterisation via a suprapubic tube varying between 12 and 35 days (15-17). Grade I and II urinary stress incontinence occurs in about 12% of patients. Subsequent TURP or bladder neck incision to treat subvesical obstruction is common, and is sometimes even performed at the time of HIFU. Post-operative impotence will occur in approximately 55-70% of patients.

11.5 Summary of experimental therapeutic options to treat clinically localised PCa
• CSAP has evolved from an investigational therapy to a possible alternative treatment for PCa in patients who are unfit for surgery or with a life expectancy < 10 years
• All other minimally invasive treatment options – such as HIFU, RITA, microwave and electrosurgery – are still experimental or investigational. For all of these procedures, a longer follow-up is mandatory to assess their true role in the management of PCa
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John

JerryB · Regular Joined: 13 Jul 2009 Posts: 43 Location: UK

John M, thanks for the information. Can you lay your hands on similar information about brachytherapy and RP, providing five-year (and maybe 10 year) biochemical disease-free survival data? Sorry, I'm probably being lazy in not searching myself, but you appear to have a splendid system of filed information.

Thanks. Jeremy

johnT · Senior User Joined: 27 Apr 2009 Posts: 176

I spelled the names wrong; no wonder you couldn't find them.
"The Prostate Cancer Treatment book" Peter Grimm and John Blasko
"Brachytherapy and IMRT" by Michael Dattoli
PCRI Insights Nov. 2003 vol 6 no 3 by Peter Grimm, John Sylvester, john Blasco.
www.dattoli.com has a lot of papers on brachytherapy and is up to date.
Search Blasko, Grimm and Sylvester and you should find data better than the 2003 data which reflects procedures done in the mid 90's; the newer procedures are much better.

I jut have a different approach in looikng at studies; most of the large studies have a unaccetaple range that I have not found to be very useful ( range from 55% to 94%, but the average is 79%) what causes these large differences in studies?
Most large studies are done by academic researchers and written by boards that comprimise because of contraversial data. I have found the studies by individual practioners more useful because they are done by doctors on the firing line treating hundreds of patients a year.
A prime example is Dr Bob Leibowitsz (compassionate Oncolong .com) who had done a lot of work on treating localized PC with HT with results that are better than any local treatment. His work is out of the mainstream and not reflected in any studies on HT. I'm not advocating his approach, but his data is compelling.
JohnT
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psa at diagnosis 40 in nov-08
gleason 6 and 7
Treatment choice seeds and IMRT

John M · Experienced user Joined: 27 Jul 2009 Posts: 59

I could find exactly what you are looking for, but here are some resources:

There are on line tables for calculating probability of being biochemical disease-free after surgery:

Han tables: http://urology.jhu.edu/prostate/hanTables.php
Also probable extent of disease based on pre-op stats, Partin tables

Tables for calculating the same from Memorial Sloan Kettering in NYC, plus tables on results of treatment for salvage radiation or hormone treatment after recurrence:

http://www.mskcc.org/mskcc/html/10088.cfm

Another calculator table from the University of Montreal:
http://www.prostatecalculator.org/

As for survival data, that's tough, because 5 or even 10 years often isn't enough time to assess the outcome of prostate cancer that is localized at diagnosis, and in addition, you need a control group because many people with early or intermediate prostate cancer will still be alive at 10 years, even with no treatment. The best controlled studies that I could find are the Scandinavian studies which compare the outcome of surgery to watchful waiting. The lastest two articles are

Bill-Axelson et al, Radical Prostatectomy Versus Watchful Waiting in Localized Prostate Cancer: the Scandinavian Prostate Cancer Group-4 Randomized TrialJ Natl Cancer Inst. 2008 Aug 20;100(16):1144-54.

Holmberg et al, Prognostic Markers Under Watchful Waiting and Radical Prostatectomy, Hematol Oncol Clin N Am 20 (2006) 845–855

These are pretty interesting, because it shows that the overall benefit treatment is modest, not as great as one might think. Surgery in patients with intermediate prostate cancer who were <65 at diagnosis, had their total death rate decreased by 20% at 10 years if they had surgery, but there was no benefit in people over 65 at diagnosis. These articles may not be free, but you can find then at the Pubmed search engine, http://www.ncbi.nlm.nih.gov/pubmed/. Trying to digest these was a lot of work, but for me was the key to deciding whether to treat or do nothing ("active survelliance"). They really need to carry out this study to 20 years of followup, because that's may be what's needed to really understand what eventually happens to us that have localized prostate cancer if we don't get treated.

Overall summaries of consensus recommendations for diagnosis and treatment options are available at

http://www.uroweb.org/nc/professional-resources/guidelines/online/

and

http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines.cfm?CFID=2176511&CFTOKEN=11489135&jsessionid=4a302e83a564791598322d2e6f1d1b4b4b5e

This is where I run out of steam. I think the followup data for radiation is good, but not as extensive for surgery. Because I decided against radiation, I didn't delve into that literature. There are probably references listed under the European Association of Urology guidelines website,

http://www.uroweb.org/nc/professional-resources/guidelines/online/

or maybe someone else knows. This is really everything I know, being what I read (plus Walsh's book) at the time I was diagnosed. But it's a couple of hundred pages of stuff, so it should keep you busy if you find any of it worth reading. If you don't have the stomach for that, the tables are the easiest to deal with. Good luck, Jerry
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John

John M · Experienced user Joined: 27 Jul 2009 Posts: 59

John T,

The abstract of the article you mentioned is pasted at the bottom of this post. There isn't anything in the article on urinary symptoms after brachytherapy, but it does give an answer for Jerry on biochemical recurrence after brachytherapy:

Biochemical control rates by risk cohort analysis (95% confidence interval): low risk, 85% (83.3-90.7%); intermediate risk, 77% (73.0-84.5%); and high risk, 45% (45.4-57.2%).

This looks to be in the same ballpark as rates after surgery, although it depends on comparing the details of the extent of disease in the patients included in the study.

John

Int J Radiat Oncol Biol Phys. 2003 Nov 15;57(4):944-52.Click here to read Links
Ten-year biochemical relapse-free survival after external beam radiation and brachytherapy for localized prostate cancer: the Seattle experience.
Sylvester JE, Blasko JC, Grimm PD, Meier R, Malmgren JA.

PURPOSE: The role of external beam radiation therapy in addition to brachytherapy continues to be scrutinized for long term control of PSA levels after prostate cancer diagnosis. METHODS AND MATERIALS: We report 10-year biochemical relapse-free survival (BRFS) on 232 patients presenting with localized prostate cancer and consecutively treated with iodine(125) (I(125)) or palladium(103) (Pd(103)) brachytherapy and neoadjuvant external beam radiation therapy. Multivariate regression analysis was used to create a pretreatment clinical prognostic risk model using a modified ASTRO consensus definition (two consecutive rises in serum PSA) as the outcome. Gleason scoring was performed by pathologists at a small community hospital. Derived risk categories are the following: low = PSA <or=10 ng/mL, Gleason sum score <7, and stage <T2c; intermediate = PSA >10 ng/mL or Gleason Score >or=7 or stage >or=T2c (1 intermediate risk factor); and high = 2 or more intermediate risk factors. Time to PSA failure (local, distant, or biochemical) was calculated and compared using Kaplan-Meier plots. RESULTS: Ten-year BRFS for the entire treatment group was 70%. Biochemical control rates by risk cohort analysis (95% confidence interval): low risk, 85% (83.3-90.7%); intermediate risk, 77% (73.0-84.5%); and high risk, 45% (45.4-57.2%). Using a risk grouping proposed by the Mt. Sinai group, the BRFS was: low risk, 84%; intermediate risk, 93%; and high risk, 57%. Grouping by the risk classification used by D'Amico, the BRFS was: low risk, 86%; intermediate risk, 90%; and high risk, 48%. CONCLUSIONS: I(125) or Pd(103) brachytherapy, as a boost combined with EBRT, continues to result in high rates of biochemical control at 10 years. Different risk group classification schemes lead to different BRFS results.
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John

JerryB · Regular Joined: 13 Jul 2009 Posts: 43 Location: UK

Thanks Johns!

Jeremy

John M · Experienced user Joined: 27 Jul 2009 Posts: 59

John T has reviewed another article comparing the side effects of surgery, brachytherapy, and radiotherapy, and posted it on the other discussion board,

http://www.healingwell.com/community/default.aspx?f=35&m=1577780

This seems relevant. The numbers in that article are a smaller than the article that I posted here, but the followup is 36 months. All of these articles depend on the skill of the surgeons and radiation oncologists, but they seems to support the conventional wisdom that radiation has a lower incidence of sexual dysfunction, as least in the first 3 years, and a lower risk of incontience, but a higher risk of urinary obstructive symptoms and bowel complaints.
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John

johnT · Senior User Joined: 27 Apr 2009 Posts: 176

An additional note to John M's post: this study was done on procedures over 10 years ago. Different protocols, such as robotic RP, better radiological technologies such guided IMRT and seed placements and better meds such as Flow max should make the results much better if the procedures were done today.
JohnT
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psa at diagnosis 40 in nov-08
gleason 6 and 7
Treatment choice seeds and IMRT

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