Noninvasive Grade 3?

The likelihood of recurrent or metastatic disease increases with the presence of one or more of the following risk factors:

Depth of invasion - Most TCCs of the bladder (75-85%) are superficial. Although the risk of recurrence is approximately 75%, most remain superficial, with only 10-15% progressing to invasive carcinoma. There is evidence to indicate that cancers that invade the lamina propria (stage T1) should not be regarded as superficial. High-grade stage T1 tumors may progress to invade muscle in 30-50% of cases. When this occurs, the prognosis is as poor as it is for those presenting initially with invasive cancer. More than 50% of patients who are treated locally for invasive cancer manifest distant metastases, and they usually die of their disease within two years.
Tumor size - Various studies have shown that tumors greater than 3 cm have up to a 35% chance of progression, and tumors greater than 10 grams are also associated with a poor prognosis.
Grade - Progression from grade I to III in patients without interval intravesical chemotherapy, cystectomy, or radiation therapy has been associated with an increased incidence of invasive disease and a decreased 5-year survival. In one study, fewer than 10% of grade I tumors but as many as 50% of grade II tumors and more than 80% of grade III tumors were found to be invasive at the time of initial diagnosis. In another study, the 5-year survival of patients with grade I tumors was 94%, but only 40% for patients with grade III tumors.
Adjacent or remote bladder mucosal changes - If there are adjacent or distant changes of atypia or dysplasia, there is a significant chance of progression to muscle invasion (more than 30% within four years of diagnosis). Carcinoma in situ (CIS), in patients with low-grade, low-stage lesions may be associated with progression to muscle invasion (greater than 80% within 4 years of diagnosis).
Multiplicity of foci - The finding of multiple tumors is seen in approximately 30% of cases and is associated with a recurrence rate that is almost one-third higher than it is in patients with single lesions. This finding is generally associated with a shortening of the average time until recurrence. Two of three patients with single lesions but nine of ten with multiple lesions developed recurrent carcinoma. In a randomized clinical trial evaluating the prognostic factors associated with recurrence of T1 cancers, the number of tumors (worst for those with three or more) at the time of presentation was most important followed, in order of importance, by the number of recurrences (significantly greater chance of future recurrence for those patients with more than one recurrence per year) and the size of the largest tumor (worst for those over 3 cm).
Upper tract obstruction has been associated with a decreased five-year survival. Patients with bilateral hydronephrosis had a 5-year survival of 31%, compared with 45% for those who had unilateral involvement and 63% for those with no hydronephrosis.
Lymphatic invasion in the lamina propria is a very poor prognostic sign, and most patients so affected die within six years. Solid (nonpapillary) lesions have a greater tendency for lymphatic invasion.
TCC involvement of the prostate - When TCC of the bladder is associated with involvement of the prostate (and it has been observed in 29 to 43% of cystectomy specimens), particularly with stromal invasion, there is a substantially increased risk of urethral recurrence. Conversely, 67% of men with urethral recurrence had prostatic TCC in cystectomy specimens. Urethral recurrence can be expected in only 1 to 4% of cases when there is no TCC in the prostate. Those patients who are not candidates for cystoprostatectomy with urethrectomy are best followed up with urethral washings. Urethroscopy is performed in those having positive cytologic results.
Laboratory tests and chromosomal abnormalities - A number of laboratory tests have been used to prognosticate tumor progression. These include tests for Thompson-Friedenreich (T) antigen expression, lectin-binding carbohydrate structures, ABH blood group antigens, oncofetal protein expression, and epidermal growth factor receptors. According to one study, "these tests have not been adopted into clinical practice to influence treatment decisions in individual patients." Chromosomal abnormalities in tumors (marker chromosomes and a large proportion of aneuploid tumor cell lines) have also been used to predict tumor recurrence or progression.

www.guideline.gov/summary/summary.aspx?doc_id=8310

Don't take the actual statistics up above as gospel, since they may reflect the natural course of the disease and not the disease course with intravestical treatment.

Your observations are certainly sobering, and is probably why the conservative Uros say yank it for best survivability. I'm going to continue researching along these lines....
Thanks, Eric

Another thing that has bothered me is the relationship between progression and reccurrance rate.  From what I understand, even though they have removed the tumor, there is still a chance that the tumor shed somehow into the bloodstream and micro-metastasis occurred which shows up from 0-3 years later.  I believe this is the primary reason that the cancer seems to spread in people post-cystectomy and that they are essentually considered "cured" if they live 2-3 years cancer free after bladder removal.

So, the progression statistics you see don't just mean a tumor going from Ta or T1 to a T2 or T3, but also include the threat of mirco-metastasis.

Thus, I believe with each reccurance you face not only the threat of actual tumor invasive progression, but of metastasis from each new tumor.  Thus a high recurrance rate or multiplicity of tumors means higher risk or progression/metastasis.

I would also assume this to mean that if you have a bladder tumor that is removed (TURB) and it does not recurr, then just like with a cystectomy after 2-3 years with a clear bladder your risk of metastasis would go to zero. Although you still have risk for recurrance which would include new risk of progression/metastasis.

I believe the risk of this metastasis (without actual tumor progression) was quoted at 5% over the 2-3 year period for a T1G3, probably lower for a TaG3, and probably almost non-existant for a TaG1.  With multiple tumors or recurrances the risk would grow.

Don't misunderstand me, metastatis is the primary risk for invasive bladder cancer and thats why with a T2-T4 tumor they usually yank the bladder and start chemo/radiation.  What I'm talking about is the *albeit* much smaller risk of metastasis from "superficial" Ta and T1 bladder tumors.

Jim-

yes, i think we're talking the same list, ie-

listserv.acor.org/archives/bladder-cancer-cafe.html

you do have to check a box to get the daily e-mails( you'll get 20+ a day--I use Outlook wizard to have them go striaght to a folder to keep my in box clean); or you can just search the archives.

reur questions- I could have been more complete in my response, partucularly now rereading your first post.

1st cystoscopy (poke and peek or p&P) found a 3 cm tumor. The TURB a week later also found a second smaller tumor- both were resected (removed and biopsied). First analysis gave a G2 finding. We asked for second opinion, and sent the slide to Mem Sloan Kettering- they bumped it to G3; another independent eval by the orig pathology dept also returned G3. ok everyone agrees! Also everyone confident it's non-invasive.

Waited three months; 2nd p&p--indications of 3 new tumors, but very small, just starting to show. 2nd TURB. It was at this point that BCG was indicated (but required 6 weeks of healing from the TURB before we could start- want to be clear of bleeding and infection). So your case seems similar. If the tumor comes back in 3 months, the aggressive nature is confirmed, and since you are catching it early, BCG is the next step. (btw, BCG is ONLY for Ta and T1 BC-- once T2(muscle invasion), you go striaght to (1) analyzing if it's anywhere else (lymph nodes, prostate, etc) and (2) barring that, take out the bladder. If (1) is positive, you might do other surgeries and/or chemo.

Ok- but you are still early. Continuing our timeline: after BCG, we couldn't for 4-6 weeks because the lining is raw and red and still recovering. After 1 month we did a P&P and while still somewhat inflamed, there was no evidence of any tumors (6 mo now since last TURB.). But then 1 month after that a new one shows up, It's about 1/2 to 1 cm, new place, "didn't look malignant, probably just a polyp due to the agressiveness of the BCG."

Not! After 3rd TURB, again staged the same. the consistency of the stagng and grading is actually reassuring. Yes this is agressive, but yes, it is staying non-invasive. Uro #1, being conservative, still wants to yank the bladder.

Enter the Web Cafe big time- I use the archives and post questions and those that have gone before point me to various references and experiences. This leads us to pursue "cancer centers" for 2nd opinions. MSKettering is very professional, but essentially says, you want to come here, we re-stage you to find out first hand the status of things. While at Mass Gen, I ask them about the BCG + interferon work, and they immediately refer us down the block to Beth Israel Deaconess where, somewhat accidentally, we talk with Dr. DeWolf who was O'Donnell's partner in all the trials of the late 90's (still on-going). (Actually the nurse practicioner there is as important, historically). they are confident that we are very good candidates for the BCG+ regimen, reminding us that there is little or no correlation between a recurrence after BCG alone, and success with interferon. We started that yesterday. oh, and btw, there was eveidence of a tumor just starting up again, new location. Very small - this being 2.5 months since last TURB.

so again, in your case, yes, if it comes back agressively, BCG is the next right thing to try. Then if it comes back aggressively after that, you are in our situation, and you need to evaluate if you have time to try BCG + Interferon (I do understand they have it in Europe, but from where you are you may have to travel to get it - it's something that is a little dicey to mix up, handle, as I understand it- ie - you just don't import it to your facility)

I was confused about the word recurrence, and its importance. I guess we have had 3, one after each TURB. But obviously only one of those following BCG. (since we've only done it once!)

oh, one more thing about why G3 is so serious. The inside of your bladder, urethra and ureters are like ONE continuous membrane (skin). Hence, if the cancer is active in this membrane, it can pretty much crop up, literally, anywhere. It usually stays in the bladder, but if not attended to , can eventually spread to those other locations which is harder to get at, obviously.

the hardest part about all this is the waiting between peeks, the wondering and the "what i don't know i don't know" piece. Again, the WebCafe has helped us interpret what we hear, and is valuable in helping us over the "what we don't know we don't know" hurdles.

Good luck, Jim,

/r Eric

Hello Eric,

Thanks for your informative reply. I think I'm a member of what you call the archive list - isn't that a sort of list-serve version of this forum? I don't post to the list, but I may confirm my registration to allow that just to lend my support.

Your suggestion about the need for cat scans and IVPs is very interesting; I don't think I've run across it before, and my doctor hasn't mentioned it. Neither did the navy doctor I spoke w/on the phone, but maybe he will during our in-person consult next month. In any event, I'll mention it to both of them. As we discussed the potential problems of a G3 tumor, including the possibility for errors regarding the staging side of the diagnosis, my wife asked how we could resolve those questions, and all I had for an answer was the second TURB the doctor is doing. But what you advise makes a lot of sense. Thanks.

If you have access to surgeons who are reticent about conducting surgery, you have access to great, intelligent medical care.

Your wife's case does seem a lot like mine. I gather she's only had the one recurrence - two tumors total, the first one and the recurrence after the first round of BCG? I'm assuming the 3 TURs are for the initial tumor removal, a second one after the pathology rpt came back G3, followed by the initial BCG, and a third after the recurrence. This must be hard on both of you. I understand I can expect similar results. I am also assuming that any recurrences that I have are most likely to also be G3. I hope the BCG+ gives you positive results. It sounds like you guys really do have a wealth of quality medical care to help guide you through this.

I also understand that the Ta side of the diagnosis is something, barring other factors, to take comfort in. But, as you indicate, the G3 side is one of those factors that casts it into doubt. Even if the Ta is confirmed regarding the current tumor, there are no guarantees about recurrences. It's as though the nature of the bladder's illness causes it to produce tumor characteristics that compete with one another - an aggressive, fast growing tumor which wants to kill you, but posititioned in a non-invasive and papillary manner as though to ward off or postpone the danger, offering an opportunity for remediation. Which side will predominate over time, and if it tends to be the Ta side, will it predominate every time?  

Thanks again for the information and support you've offered.

Best of luck to both of you. Please also let me know how your wife does in August.

r/

Jim

Hi Jim-

Yes, hi grade, Ta is one of the diagnoses. The irony of getting this designation is that because you "got it early" the decision is almost harder - To remove the bladder , or not. High grade wants to kill you, and the surest longevity is bladder removal (RC), but....

My wife has the same diagnosis, and here's our history so far: age 58, spouse has superficial TCC, non-invasive(Ta), no CIS, but high grade; 3 TURs and 1 BCG course since 6/2005; starting 2nd BCG + interferon Jul 06 --

After my wife had one round of BCG, then a "recurrence," followed by a TUR showing exactly the same pathology (hi grade TA, no CIS, no invasion), our local Uro nevertheless recommended RC, Indiana Pouch, "but you've got time, please get a second opinion." The inital shock, was big.

We have gotten 4 second opinions! one from a chief of pathology, three from Uro surgeons. The surgeons, to our surprise, are not keen to yank out bladders. They have each taken great pains to make sure we understand how major a thing bladder surgery is, more about the risks of complications than the surgery itself. Sure, taking out the bladder is the surest was to eradicate early stage, high grade cancer. But complications can be something you'll live with forever. As you'll see if you search these archives, the experiences are all over the map ( i.e. - positive and negative).

But again, high grade wants to kill you, and you must stay on top of it. Some believe that BCG only puts off the inevitable, but others have put the cancer at bay for > 5 years. My non-professional, approximate reading is that you have a 50% chance BCG or BCG w/ interferon will work to arrest the cancer, and maybe another 50% (meaning 25% net) that you'll actually kill it long term without the need to remove the bladder. I also understand that CIS is more worrisome than papillary transitional cell carcinoma.

With high grade, Your uro should also be taking cat scans and IVPs (looking at the kidneys) to identify other things that could be going on.

We also have had this frustration that most studies we see don't seem to differentiate much between Ta and T1 . But in a meeting w/ Dr Kaufman, Chief of uro-Pathology at MassGH, he indicated there is a BIG difference between Ta and T1...

Jim, if you are into web "surfing" be sure to also monitor or search the archives that you can get to thru the Web Cafe - it's a separate discussion list - requires additional "registration."

Let us know of your progress and good luck,

eric D.