So is that a good study?

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Tony Crispino
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Date Joined Dec 2006
Total Posts : 8128
   Posted 8/24/2010 9:52 PM (GMT -6)   
The following links will hopefully help define how stringent studies are done. The first link is from the US Preventitive Services Task Force (USPSTF) This is the manual for determining how studies are to be classed, how they are to be documented, and how the data is to be assessed.

www.uspreventiveservicestaskforce.org/uspstf08/methods/procmanual4.htm

The following document is a simplified description as applied to prostate cancer from the PCRI:

www.prostate-cancer.org/pcricms/sites/default/files/PDFs/ls12-3_p6-7.pdf

We see a lot of studies posted here. And most are not proof of anything. In fact, most are level II-2 or lower assessments.

Here is the rating system (Section 4.3 of the USPSTF manual):
The Task Force recognizes that research design is an important component of the validity of the information in a study, for the purpose of answering a key question. Although RCTs cannot answer all key questions, they are ideal for questions of the benefits or harms of various interventions. Thus, for these questions, the current Task Force endorses a slightly revised version of the "hierarchy of research design" used by the second Task Force:

The various Levels of data:
I: Properly powered and conducted randomized controlled trial (RCT); well-conducted systematic review or meta-analysis of homogeneous RCTs
II-1: Well-designed controlled trial without randomization
II-2: Well-designed cohort or case-control analytic study
II-3: Multiple time series with or without the intervention; dramatic results from uncontrolled experiments
III: Opinions of respected authorities, based on clinical experience; descriptive studies or case reports; reports of expert committees

Level 1 data is very strict and is considered "proof" and anything below it is varied levels of evidence. Most local therapies lack Level I assessment. For example, the MSK nomograms are based on Level II-2 information.

I hope this helps putting studies into perspective.

Tony
Disease:
Advanced Prostate Cancer at age 44 (I am 48 now)
pT3b,N0,Mx (original PSA was 19.8) EPE, PM, SVI. Gleason 4+3=7

Treatments:
RALP ~ 2/17/2007 at the City of Hope near Los Angeles.
Adjuvant Radiation Therapy ~ IMRT Completed 8/07
Adjuvant Hormone Therapy ~ 28 months on Casodex and Lupron.

Status:
"I beat up this disease and took its lunch money! I am in remission."
I am currently not being treated, but I do have regular oncology visits.
I am the president of an UsTOO chapter in Las Vegas

Blog : www.caringbridge.org/visit/tonycrispino

Postop
Regular Member


Date Joined Feb 2010
Total Posts : 385
   Posted 8/25/2010 1:04 AM (GMT -6)   
That link doesn't mention the most important randomized control trial (level 1 evidence) of prostate cancer treatment by far:

N Engl J Med. 2005 May 12;352(19):1977-84.
Radical prostatectomy versus watchful waiting in early prostate cancer.
Bill-Axelson A, Holmberg L, Ruutu M, Häggman M, Andersson SO, Bratell S, Spångberg A, Busch C, Nordling S, Garmo H, Palmgren J, Adami HO, Norlén BJ, Johansson JE; Scandinavian Prostate Cancer Group Study No. 4.

Hematol Oncol Clin North Am. 2006 Aug;20(4):845-55.
Prognostic markers under watchful waiting and radical prostatectomy.
Holmberg L, Bill-Axelson A, Garmo H, Palmgren J, Norlén BJ, Adami HO, Johansson JE; SPCG-4 Study Group.

This study now has followup going out to 12 years, comparing surgery to watchful waiting. There is a surprisingly modest decrease in prostate cancer specific mortality with surgery compared to watching in patients under 65 at diagnosis; for those over 65 there is no benefit, as the death rate was the same in the control group and the surgery group. This remains the best level 1 study of treatment for prostate cancer. Personally, I think that there may be more benefit from surgery if the followup could be someday extended out to 20 years, but that is pure speculation. Also, it is possible that surgery might save men from needing things like hormone treatment, even when it doesn't actually save their life. Nevertheless, this isn't simple. No question that in many cases, men who get prostate cancer treatment are not saving their life. A few will get treated and die of prostate cancer anyway. Many will die from something else no matter if they get their prostate cancer treated or not.

The two studies of PSA screening published last year are also level 1. The American study is limited because a lot of the men in the control group actually had PSA measured, and there was no significant difference betwee the groups. The European study is better conducted, and shows a small benefit from PSA screening, but doesn't have a long enough followup period because PCa can be so slow to develop.

I agree that uncontrolled unrandomized studies are not proof of anything, and these studies make up the vast majority, 99+% of prostate cancer studies. This is a disease where the majority of men can do very well for some years with no treatment at all. So, if there is a study of a particular treatment, with no comparison to a control untreated group, and most of the patients do well for several years what does it mean? Probably nothing.

An38
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Date Joined Mar 2010
Total Posts : 1152
   Posted 8/25/2010 1:36 AM (GMT -6)   
Yes this is very useful Tony, thank you. But it these are guidelines I think or will the authors of academic papers now have to state clearly where their paper falls in this pyramid? Or will readers have to make their own minds up.

An
Husband's age: 52. We live in Sydney Australia.
Family history:
Maternal grandfather died of prostate cancer at 72. Maternal uncle died of prostate cancer at 60. Because he is the third generation to be diagnosed he has hereditary PC.
PSA history:
Aug07 - 2.5|Feb08 - 1.7|Oct09 - 3.67 (free PSA ratio 27%)|Feb10 - 4.03 (free PSA ratio 31%) |Jun10 - 2.69
DRE normal
Biopsy 28/4/2010: results, negative for a diagnosis of PC however 3 focal ASAPs “ suspicious but not diagnostic for prostatic adenocarcinoma."
Review of biopsy by experienced pathologist, results,
1 out of 12 core diagnosed with 10% of Gleason score 3+3 cancer (left transitional)
1 out of 12 cores with ASAP (left apex), suspicious but not diagnostic of cancer

Nerve sparing RP on 20th August 2010 at St Vincent’s with Dr Stricker.
Post-op pathology
Final Gleason score: 3+4
Margin involvement: Nil
Extraprostatic extension: Nil
Multifocal, with involvement in the Peripheral, apex, fibro-muscular and transitional zones.

Post Edited (An38) : 8/25/2010 12:39:17 AM (GMT-6)


Tony Crispino
Veteran Member


Date Joined Dec 2006
Total Posts : 8128
   Posted 8/25/2010 1:48 AM (GMT -6)   
It's still imperfect. Accounting for risk is not as clearly defined as it should be, although I agree, the longer the term the more telling a study is. I saw Dr. Vogelzang stress last week that ten year studies don't go far enough and that the risks INCREASE with time in prostate cancer. It was fascinating looking at the graphs and the separation from years 8 and beyond on the various studies. The interesting point he makes is that while a disease starts out low risk, it can change in 15 years to high risk. I have seen cases like this. Doing well for 12 years is not an issue for a 64 yo typical diagnosis. If progression occurs at this point there is plenty to keep it from resulting in death by PCa. Under age 64 that is not so simple...

Great observations Postop...

Tony
Disease:
Advanced Prostate Cancer at age 44 (I am 48 now)
pT3b,N0,Mx (original PSA was 19.8) EPE, PM, SVI. Gleason 4+3=7

Treatments:
RALP ~ 2/17/2007 at the City of Hope near Los Angeles.
Adjuvant Radiation Therapy ~ IMRT Completed 8/07
Adjuvant Hormone Therapy ~ 28 months on Casodex and Lupron.

Status:
"I beat up this disease and took its lunch money! I am in remission."
I am currently not being treated, but I do have regular oncology visits.
I am the president of an UsTOO chapter in Las Vegas

Blog : www.caringbridge.org/visit/tonycrispino

John T
Veteran Member


Date Joined Nov 2008
Total Posts : 4268
   Posted 8/25/2010 10:06 AM (GMT -6)   
The problem with strict randomized, double blind studies in PC is that they don't happen. How does one randomized patients to get surgery, radiation or nothing? The researcher will also know which treatment the person has had, and we know absolutely that this affects the study results. The only true studies are randomized and researchers don't know what treatments the patiens have had and this just won't happen, so we have to accept other studies.
As far as length of time, all primary treatments except HIFU have a very flat or declining reoccurrance rate at 5 years. This is expecially valid for low risk PC. High risk PC can and does reappear at any time after treatment, but also has a declining reoccurrance rate at 5 years.
The fact is that I'm not going to wait 25 years to get data before I use a promissing therapy. This will always result in being 25 years being the technology curve, which is a most certain to produce a less favorable outcome.
JT

64 years old.

PSA rising for 10 years to 40, free psa 10-15. Had 5 urologists, 12 biopsies and MRIS all neg. Doctors DXed BPH and continue to get biopsies yearly. 13th biopsy positive in 10-08, 2 cores of 25, G6 less than 5%. Scheduled for surgery as recommended by Urological Oncologist.

2nd Opinion from Dr Sholtz, a Prostate Oncologist, said DX wrong, pathology shows indolant cancer, but psa history indicates large cancer or metastasis. Futher tests and Color Doppler confirmed large transition zone tumor that 13 biopsies and MRIS missed. G7, 4+3, approx 16mmX18mm.

Combidex MRI in Holland eliminated lymphnode mets. Casodex and Proscar reduced psa to 0.6 and prostate from 60mm to 32mm. Changed diet, no meat and dairy. All staging tests indicate that tumor is local and non agressive. (PAP, PCA3, MRIS, Color Doppler, Combidex, tumor reaction to diet and Casodex, and tumor location in transition zone). Surgery a poor option because tumor is located next to the urethea and positive margin is very likely; permanent incontenance is also high probability with surgery.

Seed implants on 5-19-09, 3 hours door to door, no pain, minor side affects are frequency and urgency; very controlable with Flowmax and lasted 4 weeks. Daily activities resumed day after implants with no restrictions. Gold markers implanted with seeds to guide IMRT.

25 treatments of IMRT 6 weeks after seed implants. No side affects at all.

PSA at end of treatment 0.02 mostly the result of Casodex. When I stop Casodex next week expect PSA to rise. Next PSA in November. Treatments and side affects have greatly exceeded my expectations. Glad to have this 11 year journey finally conclude.

JohnT


Tony Crispino
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Date Joined Dec 2006
Total Posts : 8128
   Posted 8/25/2010 10:49 AM (GMT -6)   
There is no requirement for "double blind" for a randomized controlled level 1 study. If patients fall within a control group are willing to accept any given therapy for the purposes of comparison then the results will be given level 1 consideration.:

For example: A prospective study today for a Gleason 6 PSA<10 patient to have surgery or active surveillance. In the surgery group they can elect to have either open or robotic. In the active surveillance group they must remain in the group until the PSA exceeds 10 or a re-biopsy discovers reason for active therapy. In this study, members remaining in the study are being studied for biochemical failure and mortality. The results would be considered level 1. If any patients pulled out for any reason, such as a patient in the AS group says "I'm done" before the criteria is met, they are excluded in the results.

Level 1 groups on testing drugs will likely require a blind arm, such as a placebo. The same is not necessary for an active physical therapy. There is a level 1 study that began last year comparing therapies. It will take ten to 15 years to report on the results. But we need that trial to be completed if the argument needs to be settled. And I think it does since there are folks comparing against other modalities using the words "best" or "better".

Single center retrospective studies leave much to be desired. They get to use what ever criteria best suits what they want to show. For example. Bruce Trock at Johns Hopkins has put out several studies recently on active surveillance. The first problem is that the study is retrospective and Trock is not a medical doctor, he is a statistician. He can set whatever criteria in the database to show whatever he wants without ever treating a patient. These studies are single center (cohort), and retrospective case-controlled. They could only be considered as Level II-2 or level II-3.

If Pat Walsh at JHU decided to register a prospective multi-center study using the criteria above that I described, he could in fact improve the quality of the Trock findings as it pertains to surgery versus active surveillance. but there would still be a bias because Walsh is a surgeon. Thus the Other study that compares multiple-modalities with active surveillance will supersede that study.

Tony
Disease:
Advanced Prostate Cancer at age 44 (I am 48 now)
pT3b,N0,Mx (original PSA was 19.8) EPE, PM, SVI. Gleason 4+3=7

Treatments:
RALP ~ 2/17/2007 at the City of Hope near Los Angeles.
Adjuvant Radiation Therapy ~ IMRT Completed 8/07
Adjuvant Hormone Therapy ~ 28 months on Casodex and Lupron.

Status:
"I beat up this disease and took its lunch money! I am in remission."
I am currently not being treated, but I do have regular oncology visits.
I am the president of an UsTOO chapter in Las Vegas

Blog : www.caringbridge.org/visit/tonycrispino

Postop
Regular Member


Date Joined Feb 2010
Total Posts : 385
   Posted 8/25/2010 10:49 AM (GMT -6)   
It is certainly possible to do randomized studies, just not double blind, because patients will always know what treatment they got.

Single blind studies are possible, because the followup information can be collected by a study member who doesn't know what treatment the study subject got--no looking for scars! That really isn't that hard to do, it just means that the person who gave the treatment to the person cannot be the person who obtains the outcome data. The only way to do a double blind study (where neither the patient nor the study person knows the treatment) is to give people sham treatment, and that'll never happen--you can't put people through fake surgery. The real reason why there are so few randomized studies because men (us!) are often unwilling to join them because we don't want to give up the right to chose our treatment.

John T is right, all of us are choosing treatments based on the evidence that's out there, because we can't wait 25 years for the definitive answer. We all have to recognize that we deciding to receive life-changing treatments with side effects when there is only very weak evidence that they are beneficial for us. Even though we can't wait 25 years to decide what to do, we may have to wait 10 or 20 years to find out if we made the correct decision.

What happens when you use "historical controls"?--that's what John T is talking about. That's when you compare your treatment to how you expect untreated people will do over the same time period. The problems with that are 1) there aren't a lot of good observational studies of untreated prostate cancer, although there are some, and 2) how do you know that your historical control group is the same as the people in your treatment group? They probably aren't. If the people in the "historical control" group have PCa that's a little bit worse than your treatment group, it will make your treatment look like it works, when really, the people you treat are actually doing better because they just have milder disease.

An example of how medical treatment can go wrong without controlled randomized studies: Hormone replacement therapy in women was the standard of care for decades for women after menopause. It was supposed to be good for them. When an adequate study was done, it was found out that it was harmful. Since this study came out, and estrogen replacement was discouraged, the national rates of breast cancer started dropping within a year.

None of this isn't to say that people shouldn't get their prostate cancer treatment, only that there needs to be randomized controlled studies--level 1 data--to prove that these treatments work and find out which treatments are the best. The science behind prostate cancer treatment is really very weak, and this needs to be said over and over and over again so that people don't give up on the difficult job of doing these critical studies. That includes us volunteering to participate in them.

Tony Crispino
Veteran Member


Date Joined Dec 2006
Total Posts : 8128
   Posted 8/25/2010 10:59 AM (GMT -6)   
Postop you responded about the same time I did. I believe that we are about the same.

What I would like to see is anybody trying a new therapy, to do so under a clinical trial. There has been a lot of argument about how unfair it is that HIFU has to undergo FDA approval through a trial. But this can and will likely be an advantage for HIFU. Because it is achieving accepted status through the FDA, it will have immediate trial results if the study so shows them to be positive in nature. of course if they not so favorable they will still show that it can be effective in cases where AS is an option.

We don't need 25 years to start reporting results. This can happen at year 5, 10, 15 etc. If a study is used to show biochemical failure rates or mortality and we need that comparison, then the longer the better the study.

When you say "we" can't wait that long, you are merely referring to "us" the already diagnosed. But the value of a long term study is typically not for "us". Men diagnosed in 15 - 25 years will certainly benefit. We have been treating PCa since before study guidelines were instituted in the '60's. It's a shame that very few studies in prostate cancer exist dating back before the '90's.

Because today, we sure could have used that data...

Tony

Postop
Regular Member


Date Joined Feb 2010
Total Posts : 385
   Posted 8/25/2010 11:28 AM (GMT -6)   
Agree. Say that there was a randomized controlled study of HIFU, and the ONLY way you could get HIFU in the US without traveling overseas and paying outrageous sums of money, was to be in that trial. People would enroll, and over the next 20 years the data would unfold and in the future, men would know if this was a good treatment or not. If, instead, it is licensed based on poor data, no one would enroll in the study because they could easily get it without being in a study, and have their insurance pay for it. So HIFU become common treatment, but no one knows if it is actually effective, because no one can organized a controlled trial.

As you say, this wasn't done for the treatments that we have. Say that you had a time machine. Go back to 1985, go to Johns Hopkins, tie Patrick Walsh in a chair, tell him that insurance companies won't pay for an open prostatectomy without level 1 evidence. The study is organized with the help of your shotgun. By 1990 enough men are enrolled. Preliminary data comes out. The initial reports show that men receiving surgery don't have a higher survival rate, but have a worse quality of life (that's what happened with the first reports from the Scandinavian study). Then in the mid to late 1990s reports come out that it can save lives (like the Scandinavian study did at 10 year followup). Insurance companies start paying for it. But now its 2010, and a 20-25 year followup study is published. We then know exactly what surgery can and cannot do. Then go back in your time machine and do the same experiment for the different kinds of radiation treatment. Repeat procedure until we have a rational approach to treating prostate cancer.

Tony Crispino
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Date Joined Dec 2006
Total Posts : 8128
   Posted 8/25/2010 11:38 AM (GMT -6)   
The good news is that most level 1 studies are sponsored. Meaning the drug company or device maker. Those enrolled don't have to pay more than the palliative and administrative costs. Most insurance companies approve clinical trials on drugs, because they only have to pay the nurse and facility expenses.

There are plenty of level II studies on therapy that are accepted by insurance companies. For example the most expensive therapies are primary/adjuvant combined therapies or proton therapy, also a radiation therapy. insurance companies cringe on these protocols. But for the most part they pay them...

Tony
Disease:
Advanced Prostate Cancer at age 44 (I am 48 now)
pT3b,N0,Mx (original PSA was 19.8) EPE, PM, SVI. Gleason 4+3=7

Treatments:
RALP ~ 2/17/2007 at the City of Hope near Los Angeles.
Adjuvant Radiation Therapy ~ IMRT Completed 8/07
Adjuvant Hormone Therapy ~ 28 months on Casodex and Lupron.

Status:
"I beat up this disease and took its lunch money! I am in remission."
I am currently not being treated, but I do have regular oncology visits.
I am the president of an UsTOO chapter in Las Vegas

Blog : www.caringbridge.org/visit/tonycrispino

Postop
Regular Member


Date Joined Feb 2010
Total Posts : 385
   Posted 8/25/2010 11:48 AM (GMT -6)   
Everyone wants the treatment they chose, right now, immediately, paid for in full by insurance. But maybe it would be better to require a higher level of evidence before treatments get approved and paid for. Device manufacturers could pay for a HIFU study, but big studies of things like surgery and radiation have to be paid for by the NIH or another government agency. We spend billions for medical treatment, very little for clinical trials.

Tony Crispino
Veteran Member


Date Joined Dec 2006
Total Posts : 8128
   Posted 8/25/2010 12:00 PM (GMT -6)   
A double edged sword, Postop. i live my life on the premise it's best "to be careful what you wish for". Patient preference goes a long way in the quality of life while battles with our insurance companies has the opposite affect..

Just a thought

Tony
Disease:
Advanced Prostate Cancer at age 44 (I am 48 now)
pT3b,N0,Mx (original PSA was 19.8) EPE, PM, SVI. Gleason 4+3=7

Treatments:
RALP ~ 2/17/2007 at the City of Hope near Los Angeles.
Adjuvant Radiation Therapy ~ IMRT Completed 8/07
Adjuvant Hormone Therapy ~ 28 months on Casodex and Lupron.

Status:
"I beat up this disease and took its lunch money! I am in remission."
I am currently not being treated, but I do have regular oncology visits.
I am the president of an UsTOO chapter in Las Vegas

Blog : www.caringbridge.org/visit/tonycrispino

proscapt
Veteran Member


Date Joined Aug 2010
Total Posts : 644
   Posted 8/25/2010 1:52 PM (GMT -6)   
Tony, you seem to have investigated the research standards fairly closely. Thanks for your perspective on this.

What do you think of the validity of the various nomograms at Sloan Kettering?

The SK online calculator that deals with the progression-free survival after RP references the following articles:

Postoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy. J Clin Oncol. 2005 Oct 1;23(28):7005-12.

Postoperative Nomogram for Disease Recurrence after Radical Prostatectomy for Prostate Cancer. Journal of Clinical Oncology 1999; 17:1499-1507.

There is also a 2009 review of the same nomogram, by mostly the same team: Stephenson, Kattan et. al., Prostate Cancer Specific Mortality after Radical Prostatectomy for Patients Treated in the PSA Era - J. CLinical Oncology, 9/10/2009?

It seems there was an initial model done in 1999, then updated in 2005, then the 2009 article compares the 2005 updated nomogram based on additional out-of-sample data. Although this is definitely not a prospective, randomized study, it seems methodologically that it's fairly robust. That said, I am not a statistician -- though I have taken a couple of stats and methods courses along the way...

thanks...
DX 10/2009 PSA pre-op 5.6, DRE negative. Clinical stage T1c
Biopsy: 6 of 14 cores positive, 10% of length positive
Robotic assisted RP 2/2010
Pathology: pT2cNx / Gleeson 3+4 / SM- / SV- / EPE- / Tumor volume 7%
PSA - post-op 0.01

Casey59
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Date Joined Sep 2009
Total Posts : 3172
   Posted 8/25/2010 2:03 PM (GMT -6)   
proscapt said...

What do you think of the validity of the various nomograms at Sloan Kettering?

proscapt,
 
Nomograms which are continually updated and revised, like Sloan Kettering's, are outstanding tools for decision making.  Unfortunately many people don't know how to read & use statistical tools.  As a simplified example, many people expect their results to be exactly the same as the average ("mean").  What they don't realize is that half the population has results above the average, and half have results below the average.  Nomograms helps one to understand the odds. 

Tony Crispino
Veteran Member


Date Joined Dec 2006
Total Posts : 8128
   Posted 8/25/2010 2:08 PM (GMT -6)   
I mentioned the MSK Nomograms in the title post here. They are based on Level II-2 information. They are a retrospective view of patient history controlled only by the parameters you enter in the nomogram you are using. MSK is a highly respected institution with various treatment methods. They have "branch" facilities through New York and have a large pool from which to draw retrospective data.

This question lines up perfectly with the post I did today on Gerry Chodak on his Medscape blog. In that link Chodak discusses the flaws on todays studies. I highly recommend taking a look at that.

Here is another video from Chodaks website www.prostatevideos.com

Study videos:
www.prostatevideos.com/understanding-clinical-research-studies/
There are links there discussing retrospective versus prospective and epidemiological studies.

Again I highly recommend the Medscape version in the other link...

Tony

proscapt
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Date Joined Aug 2010
Total Posts : 644
   Posted 8/25/2010 2:51 PM (GMT -6)   
Hi, Tony

I just watched the medscape version of the Chodak link. It's very clear. Thanks.

Having watched that, I think two different kinds of methodological issues are going on, and we need to tease them apart.

Chodak is talking about the fact that the Kaplan Meier estimates are relatively meaningless if the range implied by the 95% confidence interval is too wide. The main reason he cites for the wide confidence interval is too few people getting all the way to the study end points. But of course the confidence interval could also be wide if there were too few people in the study to begin with, or if in fact the impact of the treatment itself is small relative to the wide range in individual progression regardless of the treatment. This is kind of a "signal to noise ratio" issue. High noise and low signal makes for a wide confidence interval.

It seems to me that this kind of issue is a problem regardless of whether or not the study is fully randomized and controlled. A randomized controlled study can also have a wide confidence interval, if the treatment effect is small or the study was too small, or the slow progression of disease did not allow enough participants to run through to one of the defined end points.

Fortunately, all the good journals report out the confidence interval as well as the estimate or projection, so it's easy, if we are careful readers, to not be fooled by this sort of thing.

So it seems we have two separate and distinct things to worry about:
- Issue #1) whether the study is randomized and controlled to preclude a bias due to who opts into which treatment or control group
- Issue #2) whether the study has a narrow enough confidence interval to make the results valuable as a basis for clinical decision making.

Again, I am not a statistician. But does this make sense? Am I missing something?
DX at age 54 12/2009
Initial clinical profile: PSA 5.6, DRE-, high pre-op PSAV. Clinical stage T1c
Biopsy: 6 of 14 cores positive, 10% of length positive
TX: Robotic assisted RP 2/2010
Pathology: pT2cNx / Gleeson 3+4 / SM- / SV- / EPE- / Tumor vol 7% / prostate vol 40cc
PSA - post-op 0.01

John T
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Date Joined Nov 2008
Total Posts : 4268
   Posted 8/25/2010 2:56 PM (GMT -6)   
I think there may be another reason for prostate cancer studies being poor as compared to those in other types of cancer.
I read a paper about a year ago in the Journal of Urology; the authors were complaining that because most urologists were surgeons, they just weren't into research and would rather do surgery. This was costing them big time because most of the grants were being given to oncologists, especially those studing different cancers. Very little grant money was going into Urology for research.
JT

64 years old.

PSA rising for 10 years to 40, free psa 10-15. Had 5 urologists, 12 biopsies and MRIS all neg. Doctors DXed BPH and continue to get biopsies yearly. 13th biopsy positive in 10-08, 2 cores of 25, G6 less than 5%. Scheduled for surgery as recommended by Urological Oncologist.

2nd Opinion from Dr Sholtz, a Prostate Oncologist, said DX wrong, pathology shows indolant cancer, but psa history indicates large cancer or metastasis. Futher tests and Color Doppler confirmed large transition zone tumor that 13 biopsies and MRIS missed. G7, 4+3, approx 16mmX18mm.

Combidex MRI in Holland eliminated lymphnode mets. Casodex and Proscar reduced psa to 0.6 and prostate from 60mm to 32mm. Changed diet, no meat and dairy. All staging tests indicate that tumor is local and non agressive. (PAP, PCA3, MRIS, Color Doppler, Combidex, tumor reaction to diet and Casodex, and tumor location in transition zone). Surgery a poor option because tumor is located next to the urethea and positive margin is very likely; permanent incontenance is also high probability with surgery.

Seed implants on 5-19-09, 3 hours door to door, no pain, minor side affects are frequency and urgency; very controlable with Flowmax and lasted 4 weeks. Daily activities resumed day after implants with no restrictions. Gold markers implanted with seeds to guide IMRT.

25 treatments of IMRT 6 weeks after seed implants. No side affects at all.

PSA at end of treatment 0.02 mostly the result of Casodex. When I stop Casodex next week expect PSA to rise. Next PSA in November. Treatments and side affects have greatly exceeded my expectations. Glad to have this 11 year journey finally conclude.

JohnT


Tony Crispino
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Date Joined Dec 2006
Total Posts : 8128
   Posted 8/25/2010 3:31 PM (GMT -6)   
Two to respond to here:

@proscapt
I agree with you. Caution should be used in ALL study levels. Most level 1 studies compare whether a treatment works or not. Most don't report on the side effects and as to whether or not that treatment is worth the study result differences. Additionally, these studies need to be multi-center to minimize as many outside influences as possible in the study. There are no Level 1 studies of any kind that run through 1 center, 1 doctor, one cohort, etc.

@JohnT
The reporting of urologists in the Journal of Urology is opinion. At best level III. I think (level 4 and beyond) the primary reason that we lack strong study information in prostate cancer is the nature of this disease being a 20 year disease. We know factually that surgery is a best option for lung cancer. But lung cancer is a fast and deadly disease. brachytherapy for lung cancer and brachytherapy for prostate cancer are two different things. It can take up to a year for any radiation to deliver the full effects of that treatment. In prostate cancer that works because almost no one dies of prostate cancer in a year, and if they do it's likely that no local therapy was going to work alone. In lung cancer we get results quicker thus validating the treatment protocols in level 1 studies is an easier task.

You have heard me say it before ~ Ten year studies in prostate cancer for localized therapies tell us very little when too many patients will die after that timeline.

Tony
Disease:
Advanced Prostate Cancer at age 44 (I am 48 now)
pT3b,N0,Mx (original PSA was 19.8) EPE, PM, SVI. Gleason 4+3=7

Treatments:
RALP ~ 2/17/2007 at the City of Hope near Los Angeles.
Adjuvant Radiation Therapy ~ IMRT Completed 8/07
Adjuvant Hormone Therapy ~ 28 months on Casodex and Lupron.

Status:
"I beat up this disease and took its lunch money! I am in remission."
I am currently not being treated, but I do have regular oncology visits.
I am the president of an UsTOO chapter in Las Vegas

Blog : www.caringbridge.org/visit/tonycrispino

goodlife
Veteran Member


Date Joined May 2009
Total Posts : 2692
   Posted 8/25/2010 9:38 PM (GMT -6)   
Even tho my head is swimming, and it's like watching a ping pong match, this is a great thread.

The net that my simple mind takes from this just because it is titled a a "study", doesn't mean the results are valid.
Goodlife
 
Age 58, PSA 4.47 Biopsy - 2/12 cores , Gleason 4 + 5 = 9
Da Vinci, Cleveland Clinic  4/14/09   Nerves spared, but carved up a little.
0/23 lymph nodes involved  pT3a NO MX
Catheter and 2 stints in ureters for 2 weeks .
Neg Margins, bladder neck negative
Living the Good Life, cancer free  6 week PSA  <.03
3 month PSA <.01 (different lab)
5 month PSA <.03 (undetectable)
6 Month PSA <.01
1 pad a day, no progress on ED.  Trimix injection
No pads, 1/1/10,  9 month PSA < .01
1 year psa (364 days) .01
15 month PSA <.01

Fairwind
Veteran Member


Date Joined Jul 2010
Total Posts : 3889
   Posted 8/25/2010 10:14 PM (GMT -6)   
Ah, but the results ARE probably valid IN THE GROUP THAT THEY STUDIED...

When the people doing the study intentionally filter the members of the group in order to get the desired results, (make themselves look good) THAT'S when the trouble starts..
Age today: 68. Married, 6', 215 pounds, active, no health issues.
PSA at age 55: 3.5, DRE negative. Advice, "Keep an eye on it".
PSA at age 58: 4.5
PSA at age 61: 5.2
PSA at age 64: 7.5, DRE "Abnormal"
PSA at age 65: 8.5, DRE " normal", biopsy, 12 core, negative...
PSA at age 66 9.0 DRE "normal", BPH, Finesteride. (Proscar)
PSA at age 67 4.5 DRE "normal" second biopsy, negative.
PSA at age 67.5 5.6, DRE "normal" U-doc worried..
PSA at age 68, 7.0, third 12 core biopsy positive for cancer in 4 cores, 3 cores Gleason 6, one core Gleason 9. Finesteride discontinued, still no urinary symptoms, never had any..From age 55 to 65 I had no health insurance.

I have a date with the robo surgeon on Sept 3 but I'm keeping my options open. I'm also looking at seeds combined with IGRT which seems to be having good results with high-risk patients..

An38
Veteran Member


Date Joined Mar 2010
Total Posts : 1152
   Posted 8/26/2010 9:05 AM (GMT -6)   
I love this thread. Hopefully it will force me and everyone else reading studies to think about how they fit into this framework.

Bias is inherent when there is money or reputation involved. Studies cost money and if insurance companies use it to sell product or a surgeon/radiation oncologist use a study to sell services either directly or indirectly then the study is inherently biased. And good studies are expensive and in the case of prostate cancer, expensive and needing a decade to do properly. So unless there is government or an unbiased source of funding to support Level I or IIa studies, we won't see many of them.

An

Tony Crispino
Veteran Member


Date Joined Dec 2006
Total Posts : 8128
   Posted 8/26/2010 9:40 AM (GMT -6)   
Well said An,

I have a very low confidence in studies below Level 1. Far too many variables. But still like Fairwind says, there is room to accept the data, but it does require room for critique.

The point I was trying to make with this thread is that studies are not necessarily facts. In fact quite the contrary. And certainly don't trust the reporter writing that newspaper article. I assure you they don't understand this thread probably at all.

Tony
Disease:
Advanced Prostate Cancer at age 44 (I am 48 now)
pT3b,N0,Mx (original PSA was 19.8) EPE, PM, SVI. Gleason 4+3=7

Treatments:
RALP ~ 2/17/2007 at the City of Hope near Los Angeles.
Adjuvant Radiation Therapy ~ IMRT Completed 8/07
Adjuvant Hormone Therapy ~ 28 months on Casodex and Lupron.

Status:
"I beat up this disease and took its lunch money! I am in remission."
I am currently not being treated, but I do have regular oncology visits.
I am the president of an UsTOO chapter in Las Vegas

Blog : www.caringbridge.org/visit/tonycrispino
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