Stage I seminoma management?
 

Came across a stage I (T2N0) pure seminoma, 7 cm with LVI. LDH elevated pre-op, B-HCG and AFP negative post-op. LDH post-op pending. Traditionally, these pts would get PA (para-aortic) RT or surveillance, although carboplatin has been a more recent option. Pooled analyses examining things such as Tumor size, rete testis involvement, LVI and age were used to help guide the decision for surveillance vs upfront RT. Later studies refuted things such as rete testis involvement as a risk factor for PA node relapse.

Nowadays the preferred recommendation from the NCCN is surveillance, unless tumor markers are elevated post-op (Stage IS). My question is, is there still any validity to using things such as tumor size or LVI to consider offering carbo or RT to patients upfront, or is surveillance pretty much the preferred option for any Stage IA/IB patient that comes through the door (regardless of tumor factors such as size or LVI)?

Presumably you're referring to the Chung paper which refuted tumor size >4cm and rete testis involvement to be risk factors for relapse. I believe institutions have largely abandoned using these criteria to officially determine whether to treat. However, everyone gets a little nervous letting a T4N0 get away with surveillance. I'm not aware of any data pertaining to LVI. Our standard has been a balanced discussion including surveillance and let them decide. If pushed, we'd prefer surveillance, but they're all category 1.

We try to have a balanced discussion. One of the things I do highlight is the potential for late relapses with seminoma and the need for extended follow up. My bias is for treatment and I let the patient know that but I also tell them that all options are reasonable choices.

The last time I looked at NCCN the cited reference showing that the traditional risk factors of size and rete testes invasion could not be validated was in Abstract form only. Moreover it seemed to be a data set at least partially from PMH. I guess my issue is that if PMH started using their published selection criteria to guide treatment, how can you validate these factors in a patient population in which they were used to select treatment. To me you would need to validate in a patient population in which management decision had not been made with the bias of the initial Warde paper. Since the reference is only an abstract there is minimal detail about the "validation cohort"

That said the fact that the initial Warde risk factors are now being stated as not useful by Warde himself (and Chung) is concerning.

Yeah, Tx can be a reasonable choice in a patient who you think may not be as compliant with the recommended surveillance program for observation given by the NCCN. By giving PA RT, you cut down the number of scans/tests they will need in F/U.

Thanks for the responses

Carbo AUC 7 x 1 is my first option. Long enough follow-up. Easy. Low toxicity. Treats contralateral in-situ disease. Still need scans, though. I agree all are fine, but I recommend: 1) chemo 2) surveillance 3) RT in that order.

Only thing with that is that NCCN does have a different F/U regimen for carbo pts vs RT pts. More frequent lab draws the first few years.

Also, just to stir the pot up, there's an editorial questioning the F/U of carbo in the JCO that accompanied the last update of EORTC/MRC study

http://jco.ascopubs.org/content/29/8/949.full

There are reasons to favor RT or surveillance over chemo, but that editorial was and is garbage. It doesn't say anything. Of course non-inferiority and equivalence are different. The statistical thresholds are different, but it does indicate it's not inferior. It's sort of arbitrary in my practice - if you tell me a treatment is non-inferior to another treatment, I'd say either are fine. If you tell me 2 treatments are equivalent, I'd say either are fine.

The idea that with 15% relapse, that 85% of patients are treated unnecessarily - that's ludicrous. The point is relapse rate is reduced with tx (either RT or carboplatin). Like saying we shouldn't treat the cuff in endometrial cancer because 85% of the women won't relapse, and there isn't a survival benefit.

Is Carbo effective? There is a 3% recurrence rate! I don't think we need to switch to a more toxic drug.

Gotta get follow-up imaging for years? Well, you have to do that with PA-strip RT, too, b/c of higher pelvic relapse right.

I mean the whole thing is utter stupidity from a guy who probably shorted the company that makes Carbo. It's rampant speculation and it really reads like double speak. He's comparing Chemo to Surveillance, but confusing Surveillance for RT. Give it a read. It's instructional on how not to make an argument.

S

Per NCCN, if you opt for Carbo or surveillance you need CT scans every 3 mo for three years. That's a lot of low dose radiation. PA field only requires x3 CT scans annually.

They updated the guidelines this past february and essentially separated those surveillance programs. Now you only need an annual CT A/P for carbo, not multiple scans a year. You still need more lab draws however.

My issue with carbo is the length of F/U. Is 6.5 years enough F/U in a case where patients are expected to live for a long time? For the rare patient who is diagnosed as Stage IS, the guidelines are still clear that you do RT, not carbo.

My personal bias is 1) Surveillance 2) RT 3) Carbo, but I'll always refer these patients to a med onc for their opinion when they get sent to me by the urologist.

Carbo is generic. I thought maybe it was because the authors were Rad Oncs :D But nope, one is a med onc and the other is a biostatistician

Thanks! I downloaded the guidelines late last year so was not up to date on the latest revision. Important to know for Louisville . . .

You're welcome. It's probably a good idea to do a last minute check of all of those guidelines. The NCCN can be pretty sneaky with their updates.

You're correct, but salvage rates in the two are not comparable. Even if you are going to see a relapse rate of >30% for Stage I with multiple adverse features, the salvage rates are excellent with chemotherapy alone. So, the question remains, can you omit treatment up front if salvage treatment is just as effective?

The best "validation" data set is from the SWENOTECA study, in which neither size, age, nor LVSI was associated with relapse risk (PMID: 21205748).

I would look into factors like tumor size, LVI, involvement of the rete testis.
The data supporting these factors as crucial in making your call are not there, but it makes sense to use the factors to guide your decision.

I would opt for 1x AUC7 carboplatin. You skip a lot of follow up CTs, which may harm your patient too and reduce his emotional stress before every next follow-up exam.

Surveillance is an option, but rather few patients in my experience actually opt for it.


Anecdote:
My last Seminoma Stage I patient WANTED radiation therapy, he declined surveillance, cause he was scared and he declined chemo, because he didn't like drugs. I tried to make it clear to him, that long term side effects of carboplatin are probably less than radiation therapy, but he wouldn't listen. He ended up getting 20 Gy in his PA field.
The most funny stuff is, that he was diagnosed with a non specific chronic colitis before radiation therapy, leading to a bit of diarrhea every now and then. After the 20 Gy he didn't have any diarrhea for the next 6 months (last follow up I made, urologist took over later on). Perhaps I killed all those lymphocytes in the bowel wall? :laugh:

Crazy stuff...

Thanks. Hadn't seen that.

The primary difference is that we do have quite an effective salvage treatment for seminoma patients relapsing under surveillance with usually Stage II disease then: you either give paraaortal and ipsilateral pelvic irradiation or 3-4x BEP.
Both treatment modalities are good and still offer 95%+ salvation in Stage IIA disease.

In endometrial cancer salvage treatment for a vaginal recurrence is going to be less effective than that and probably related to a lot of side effects.


The real question is:

Would you rather treat all 100 patients with 20 Gy paraaortal irradiation or only treat the 15 patients, that will recur with 30-36 Gy of paraaortal and ipsilateral pelvic irradiation, while the other 85 guys won't need any therapy at all?
Tough call if you ask me, bearing in mind that the potential side effects of 30-36 Gy paraaortal & ipsilateral pelvic irradiation are not that much higher than those of 20 Gy paraaortal irradiation.

This is the main reason, I have difficulties nowadays to offer 20 Gy paraaortal irradiation in Stage I patients. I usually opt for Carboplatin, if I feel there are high risk features involved or the patient wants treatment. Otherwise: surveillance.