Diagnosed Stage 1A - Embryonal Carcinoma - Decision to make:

[don_con]

Hey All,

New guy checking in, and I apologize if I double up on a similar question before. I found one very related thread here (http://www.tc-cancer.com/forum/forum...choices/page2). I am presented with a very similar life decision to make. The details upfront:

• 34-year-old male (in otherwise great health)
• 08 Aug 17 - Presented to Emergency Room with testicular pain, ultrasound confirmed mass
• Pre-Operative Blood work:
  • AFP = 2.2ng/mL (0.0-8.3) - WNL
  • hCG = 1 mIU/ML (0-3) - WNL
  • LDH = 255 IU/L (121-224) - HIGH
• Pre-Operative Imaging:
  • Abdominal CT = Confirmed left testicle mass, everything else suggested ALL CLEAR of any potential METs***
  • Thoracic X-Ray = Clear
• 09 AUG 2017 - Referred and saw Urologist next day
• 12 AUG 2017 - Completed a Left I/O (excellent surgical experience)
• Post-Operative Pathology Report
  • Embryonal Carcinoma with Germ Cell In Situ (5.0 cm in greatest dimension, 3.8x3.5 cm additional dimensions)
  • Confined to left testicle, no evidence inside spermatic cord
  • NO evidence of LVI
• Post-Operative (2 weeks after) Blood Work
  • AFP = 1.3 ng/mL (0.0-8.3) – WNL, Lower compared to pre-op
  • hCG = <1 mIU/mL (0-3) – WNL, Lower compared to pre-op
  • LDH = 168 IU/L (121-224) – WNL, Lower compared to pre-op

****CT Scan confirmed an undiagnosed, asymptomatic, congenital right kidney issue, specifically Hydronephrosis with ureteropelvic junction obstruction. I was subsequently referred for a MAG-3 nuclear med scan to gauge the function level of my right kidney. Results show that my right kidney is absorbing, filtering, but not draining nearly as fast as it should. My creatinine levels are slightly elevated, but after checking bloodwork for the last 6-7 years they haven’t fluctuated. I have second nephrologist consult 22 SEPT.

So, with all that, my first oncologist appointment she informs me I am Stage 1A. She initially recommended chemo (BEP) based on the embryonal carcinoma relapse rates (she quoted 15-40% recurrence). We both had concerns on the chemo’s impact on my kidneys, especially since at that time we were still a bit in in the dark regarding my kidney situation.

A few days after, she consults a colleague (unnamed) at Indiana University and after this consult she calls me to modify her original recommendation. She readily admits she sees the value to consulting to a center of excellence, and their recommendation is for me to go into active observation.

So my dilemma is below, option 1 vs option 2:

OPTION #1 - Proactively do 1 Round of BEP to lower my 15-40% chance of relapse down to less than 5% ( My GP and Nephrologist are leaning towards this option)

PROS:

• Highly decrease my chances of RPLND Surgery
• Highly decrease my chances of needing 4xBEP in the event of a relapse (potentially sparing any potential kidney damage from doing a full 4 cycles)
• Highly decrease my general worrying, concern, fretting from “waiting and seeing”

CONS:

• Pump poison throughout my body and deal with all the known side effects of chemo
• Increase my general concern/fretting over the UNKNOWN effects of BEP long term (cardio/lung/immune function)
• Impact at work, impact my wife etc.
• Risk chance of impacting my kidney(s), to what degree, unknown (only literature i've been able to find on Pubmed showed a 4% of people showed kidney damage with BEP)

OPTION #2 – Following Oncologist’s recommendations and go into active observation, Version 2.2017 of the NCCN Guidelines for Nonseminoma’s (This is also currently be advised by 2 other oncologists at Indiana University via telephone consult from my oncologist, so a total of 3 oncologist recommending this option)

PROS:

• Avoids pumping poison into my buddy
• Avoids dealing with all the side effects, known and unknown
• Life goes on as “normal”, no disruption to life or work
• I work from home, and live 3 miles away from an excellent healthcare system in D.C. (and all my specialists), so I have ZERO concerns adhering to the NCCN observation guidelines

CONS:

• Stress of “wait and see” of the 15-40% recurrence rate
• If I relapse, highly likely I would need 4xBEP and possibly surgery depending on presentation
• According to Sagalowsky (2000), post-chemo therapy debulking can be very difficult.
• Concerns for the impact of kidney(s) on having a full 4 cycles as opposed to have just one (option #1)
• If recurrence happens, overall life impact of surgery and/or chemo on work and marriage etc.

OPTION #3 – RPLND which neither my Urologist nor Oncologist to this point has recommended


For those interested in some of the research highlights I’ve been able to pull from the literature in PubMed related to my case, list and references below

1. The four primary risk factors for relapse of a EC Stage 1A: vascular invasion of the primary tumor, lymphatic invasion, the presence of embryonal carcinoma, and the absence of yolk sac tumor (Beck, 2010);
   1. A prospective MRC trial based on these prognostic variables found the presence of at least three of these four factors to be predictive for relapse in 48% of patients
   2. Vascular invasion was the predominant finding.
   3. Conversely, those patients with zero to two risk factors were found to recur on surveillance about 20% of the time

2. Of the patients who started off with clinical stage 1 disease, 74% remained continuously free of disease (Sagalowsky, 2000);

1. Those who relapsed did so within 2 years. Testis cancer grows rapidly and has the shortest doubling time of any tumor.
2. The factors that best predicted relapse were vascular channel invasion first of all and then predominance of embryonal carcinoma on histology.

3. …Data underscore the excellent outcomes achieved with surveillance and further validate surveillance as a standard management option for CS I nonseminoma.(Daugaard et al., 2014)

1. As anticipated, LVI strongly predicted for recurrence (relapse rate was 43% for those with LVI v 26% for those without LVI)
2. It should be noted that most prior studies found relapse to be associated with EC predominance varying from 50% to 100% rather than just the presence versus absence of any EC within the primary tumor.

4. data on the toxicities of one to two cycles of BEP are limited. Nearly all data are extrapolated from BEP × 3 (Feldman, 2014):

1. It is reasonable to expect that the same long-term toxicities of cardiovascular disease, cardiovascular disease risk factors, renal insufficiency, infertility, hypogonadism, and secondary malignancies, including leukemia, observed after three cycles of BEP will also occur after one or two cycles of BEP, although hopefully with a lower frequency. S
2. Since adjuvant chemotherapy with two cycles of BEP spares only one cycle beyond what patients relapsing on surveillance would receive (BEP × 3) and exposes 50% of patients to chemotherapy unnecessarily, I recommend a single cycle of adjuvant BEP if adjuvant chemotherapy is given.

5. Kidney damage was only present within 4% of those who did BEP (didn’t define DAMAGE, or grade the function) – needs source

6. A quote from this board from another member, from Dr. Einhorn "With embryonal predominant disease but no vascular invasion, you have a 70% cure rate with orchiectomy alone."





References:

Beck, S. D. W. (2010). Management options for stage 1 nonseminomatous germ cell tumors of the testis. Indian Journal of Urology : IJU : Journal of the Urological Society of India, 26(1), 72-75. doi: 10.4103/0970-1591.60455

Daugaard, G., Gundgaard, M. G., Mortensen, M. S., Agerbæk, M., Holm, N. V., Rørth, M., . . . Lauritsen, J. (2014). Surveillance for Stage I Nonseminoma Testicular Cancer: Outcomes and Long-Term Follow-Up in a Population-Based Cohort. Journal of Clinical Oncology, 32(34), 3817-3823. doi: 10.1200/jco.2013.53.5831

Feldman, D. R. (2014). Treatment Options for Stage I Nonseminoma. Journal of Clinical Oncology, 32(34), 3797-3800. doi: 10.1200/jco.2014.56.8006

Sagalowsky, A. I. (2000). Treatment options for clinical stage 1 testis cancer. Proceedings (Baylor University. Medical Center), 13(4), 372-375.

[biwi]

You pretty much have it all laid out. You can't make a wrong choice between 1xBEP, RPLND or surveillance in this situation. Its really up to you.

One nitpick, if you do have a recurrence, it is highly unlikely you will need 4xBEP. It would be 3xBEP unless the recurrence was caught at a very late stage, which is just about impossible with the surveillance schedule you will be on.

[RJKD]

If you are 100% EC with no LVI, you have an approximate 45% risk of relapse from some large studies done at Princess Margaret in Toronto, not 15-40%. The 30% relapse rate that Einhorn quotes is EC predominant disease, but NOT those with 100% EC. I'd go RPLND in this situation. It's a good option with many advantages that many of your doctors are overlooking. Surveillance doesn't avoid chemo. In fact, that route actually increases the risk of a higher number of cycles of chemo. It's easy for a doctor to say surveillance.

[RJKD]

Biwi is correct. Highly unlikely you will need 4 x BEP on relapse. The overwhelming majority need 3 x BEP (or 4 x EP). The 3 x BEP vs 4 x EP is in itself a very difficult choice to make. Also, given your kidney disease, they may push you to avoid Bleomycin as there is a higher risk of lung disease with those with chronic kidney disease (Bleomycin is cleared through the kidneys).

If you relapse, there is a 25% chance you will also need RPLND.

Dr de Witt, a renowned TC expert in the Netherlands, favors 1 x BEP in patients with stage 1b non-seminoma because in the 50% of people that relapse, their burden of treatment will be much greater (triple the amount of chemo, and then the possibility of a large surgery). I know you are not stage 1b, but stage 1a. However, with stage 1a 100% EC, the relapse rate is almost identical to that of a stage 1b non-seminoma patient.

[Arch]

I think it comes down to what you're comfortable with. I was recently faced with the same basic choice (though my pathology was different than yours - Stage 1B mixed nonseminoma). I ultimately decided that I wanted to reduce the risk of needing chemo (either adjuvant now, or later upon potential relapse) to reduce the risk of incurring the lasting side effects. So I ended up going RPLND for primary treatment. It took me a long time (and a lot of thinking) to finally reach that decision, though.

[don_con]

If you are 100% EC with no LVI, you have an approximate 45% risk of relapse from some large studies done at Princess Margaret in Toronto, not 15-40%. The 30% relapse rate that Einhorn quotes is EC predominant disease, but NOT those with 100% EC. I'd go RPLND in this situation. It's a good option with many advantages that many of your doctors are overlooking. Surveillance doesn't avoid chemo. In fact, that route actually increases the risk of a higher number of cycles of chemo. It's easy for a doctor to say surveillance.

Hey RJKD - thanks for the info above. Do you have any published literature on the studies done @ PM in Toronto? My oncologist spoke to Einhorn about my case, and one of his colleagues, and both recommended surveillance. My urologist office also has a IU-Fellowship trained surgeon who has done RPLNDs, so that is nice to know as I consider my options.

And @ Biwi/RJKD - thanks for the correction on number of cycles.

[RJKD]

Hey RJKD - thanks for the info above. Do you have any published literature on the studies done @ PM in Toronto? My oncologist spoke to Einhorn about my case, and one of his colleagues, and both recommended surveillance. My urologist office also has a IU-Fellowship trained surgeon who has done RPLNDs, so that is nice to know as I consider my options.

And @ Biwi/RJKD - thanks for the correction on number of cycles.

Einhorn always recommends surveillance. I understand his position on this as he wants to only treat when he knows he has to. The problem is, when one knows they have to treat, the treatment is far more punishing. Very often, I see a patient of his relapse and the thinking from the doctors is "hey, now you'll be cured with 3 x BEP like we said". To me that's where I have a problem. The 3 x BEP is a very difficult treatment and the end result is not the same in my mind. You have about a 40% chance of needing this. It's a coin flip. I wouldn't want a coin flip deciding if I need 3 x BEP!! I'd do my best to try to avoid it with an RPLND. Put the odds more in your favor.

[RJKD]

I'll have to go searching for the studies done at Princess Margaret. From what I remember, they had 33 stage 1a Embryonal patients and 15 or so relapsed.

[don_con]

I'll have to go searching for the studies done at Princess Margaret. From what I remember, they had 33 stage 1a Embryonal patients and 15 or so relapsed.

Thanks - if you remember any of the details (authors, title, etc) I can try PubMed on my end as well.

[RJKD]

Refer to this study:

Non-risk-adapted surveillance in clinical stage I nonseminomatous germ cell tumors: the Princess Margaret Hospital's experience.

[don_con]

Refer to this study:

Non-risk-adapted surveillance in clinical stage I nonseminomatous germ cell tumors: the Princess Margaret Hospital's experience.

Found it, and found the sources:

"Our data confirm the prognostic significance of primary tumor LVI ( p < 0.0001) but suggest that pure EC (not percentage ranges) is as important ( p = 0.02) [2,12,16]."

Both risk factors (LVI and EC) with low p-values.



[2] Read G, Stenning SP, Cullen MC, et al. Medical Research Council prospective study of surveillance for stage I testicular teratoma. Medical Research Council Testicular Tumors Working Party. J Clin Oncol 1992;10:1762–8.

[12] Albers P, Siener R, Kliesch S, et al. Risk factors for relapse in clinical stage I nonseminomatous testicular germ cell tumors: results of the German Testicular Cancer Study Group Trial. J Clin Oncol 2003;21: 1505–12.

[16] Heidnreich A, Sesterhenn IA, Mostofi FK, Moul JW. Prognostic risk factors that identify patients with clinical stage I nonseminomatous germ cell tumors at low risk and high risk for metastasis. Cancer 1998;83:1002–11.

[Addictedangel]

My husband and I just faced the same options.. He is 1a as well, 60%yolk 40% ec. We chose to do 1 round of bep for multiple reasons...
the risk of relapse is about 30% for him, and he is somewhat of a worrier so the stress of the unknown just isn't something we want to go through.

The only big con we had, which I don't see mentioned a lot (because it's rare..then again so is tc) is that your risk of getting leukemia down the road goes up to 6-20% (depending how many rounds of chemo you do). This was confirmed by our oncologist to be a side effect of the etoposide.

We decided to do the 1 round now in the hopes that he doesn't have to do more (riskier) rounds if he relapsed.

[RJKD]

My husband and I just faced the same options.. He is 1a as well, 60%yolk 40% ec. We chose to do 1 round of bep for multiple reasons...
the risk of relapse is about 30% for him, and he is somewhat of a worrier so the stress of the unknown just isn't something we want to go through.

The only big con we had, which I don't see mentioned a lot (because it's rare..then again so is tc) is that your risk of getting leukemia down the road goes up to 6-20% (depending how many rounds of chemo you do). This was confirmed by our oncologist to be a side effect of the etoposide.

We decided to do the 1 round now in the hopes that he doesn't have to do more (riskier) rounds if he relapsed.

The risk of leukemia down the road is not 6-20%. The Etoposide can cause AML. Etoposide induced AML tends to present in the first 5 years post-chemo. Actually, usually even sooner and within the first 2-3 years post-chemo. The risk of Etoposide induced leukemia is about 1 in 200 for those that do 3 x BEP.

[RJKD]

Also, if the risk of leukemia was that high, then EVERYONE would be getting RPLNDs. Absolutely everyone, even those with an initial 10% risk of relapse.

[RJKD]

The risk of Etoposide-induced leukemia from Stem Cell transplants is about 3%. The etoposide dose for these patients is VERY high.