Clinical Case Management - Locally Advanced Penile Cancer

[dieABRdie]

I am presenting a patient at tumor board with penile cancer. I have treated a couple of these in residency but there is some disagreement between myself and the other radiation oncologist here on field design, so I would like to see what other people would do.

Diagnosis: Invasive moderately differentiated squamous cell carcinoma

Staging: pT3 (invasion of corpora cavernosa), pN3 (ENE), cM0 (by PET)

Previous treatment/workup: Biopsy and penectomy with right inguinal lymph node dissection. The tumor was 2.2 cm but the surgical margins were clear. 2/3 lymph nodes were positive for metastatic squamous cell carcinoma from the right inguinal region. The larger lymph node measures 5.5 cm with extranodal tumor extension. He did have a PET scan which was negative for any evidence of metastatic disease. He underwent 4 cycles of Taxol/ifosfamide/Platinum with Cispatin changed to Carboplatin after cycle 3.

I will note that I am seeing him after his staging workup and treatment were generally butchered. Let us go with the above summary.

Questions:

In general what treatment would he need at this point?
I am sure we all agree he needs adjuvant radiation… how would you design your volumes and what dose do you give to each volume?
Any role for concurrent chemotherapy?

The other radiation oncologist here was just going to do nodal irradiation to bilateral inguinal nodes and the pelvic nodes. They felt that the primary site was already treated. I am not so sure that I should not give some dose to the primary site as well, although it is been resected with negative margins. Maybe go to a lower dose?
My plan was to treat the primary site, inguinal and pelvic lymph nodes bilaterally to 45-50.4 Gy, no boost to the primary because it was already resected with negative margins. I would treat the right inguinal nodes where there was extranodal extension to somewhere between 65 to 70 Gy or as high as tolerated. NCCN guidelines consider T3-4 or node positive as surgically unresectable and recommend at least 45-50.4 Gy to the whole penile shaft, pelvic lymph nodes and bilateral inguinal lymph nodes with a boost to the primary lesion to 60-70Gy. He probably should have concurrent chemotherapy although having received 4 cycles of neoadjuvant that is probably not possible.

I would appreciate any comments.

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[evilbooyaa]

Only ever treated one, but in the regionally recurrent setting. I'm very confused at the adjuvant chemotherapy (including the fact it was used and the regimen) used but I won't pretend to be an expert in this.

I would keep it simple and offer something that is acceptable within NCCN guidelines.

I would try to give concurrent chemoRT especially if you're taking ECE to 65-70, with the understanding that tolerance of cis or carboplatin will likely be less.

Interesting case. I'd have to crack books and guideline papers for something like this.

 

[medgator]

Interesting case. I'd have to crack books and guideline papers for something like this.

Which is why they used to love it on the boards even though I never saw one in training and maybe one in practice

 

[scarbrtj]

Was this HPV associated? I would allow myself a bit lower doses if so. Also, would allow a lower dose on account of all that chemo. I'm not sure we know that more than 60 Gy is needed for subclinical/postop disease in penile cancer. More than 60 Gy to the groin can be very toxic lymphedema-wise. I do not like going much above 50 there. I got the feeling I'd be aiming for 45Gy w/IMRT for elective nodal coverage w/ a 9Gy boost to the ECE region as I was reading your case. There's going to be enough dose spillover into the penectomy region I think you're good there esp w/wide neg margins.

 

[dieABRdie]

Only ever treated one, but in the regionally recurrent setting. I'm very confused at the adjuvant chemotherapy (including the fact it was used and the regimen) used but I won't pretend to be an expert in this.

I would keep it simple and offer something that is acceptable within NCCN guidelines.

I would try to give concurrent chemoRT especially if you're taking ECE to 65-70, with the understanding that tolerance of cis or carboplatin will likely be less.

Interesting case. I'd have to crack books and guideline papers for something like this.

You should be confused because his overall management to date was butchered.
1) Biopsy and partial penectomy December 2018. Before surgery had a CT of the abdomen/pelvis showing a giant necrotic right inguinal node that was apparently ignored. No full sytemic staging (no PET).
2) Sent to a medical oncologist January 2019 that gave the above regimen.
3) PET done after chemotherapy (June 2019) showed residual disease in the right inguinal region but no new disease.
4) Went back to urologist who did penectomy in August 2019 who did a right inguinal lymphadenectomy.
5) Tried to convince patient to get radiation there in their center but they are 3 hours from patient's home... patient refused and is now with me.

I'm getting a lot of this out here....

I couldn't find any consensus guidelines. Seems like the best resource is NCCN and the CCF book so I appreciate the input.

 

[dieABRdie]

Was this HPV associated? I would allow myself a bit lower doses if so. Also, would allow a lower dose on account of all that chemo. I'm not sure we know that more than 60 Gy is needed for subclinical/postop disease in penile cancer. More than 60 Gy to the groin can be very toxic lymphedema-wise. I do not like going much above 50 there. I got the feeling I'd be aiming for 45Gy w/IMRT for elective nodal coverage w/ a 9Gy boost to the ECE region as I was reading your case. There's going to be enough dose spillover into the penectomy region I think you're good there esp w/wide neg margins.

Excellent point. I do not believe it was tested so maybe I can have the path reviewed. The other doc did not want to go above 60 either.

 

[taserlaser]

Had a run of a few cases toward the end of residency. Without digging too much into the literature, I will share my experience:

As much as I can remember, one gentleman developed nodal recurrence (initially node negative). Dissected, adjuvant RT, developed cutaneous (field margin, thigh) and nodal in field recurrence progressing even towards the end of RT. Chalking it up to bad biology but that influenced my attending to be a lot more aggressive/in favor of adjuvant nodal treatment. He did not get chemo as your patient above.

Second patient soon after this one - partial penictomy, clear margins. Pre-treatment MRI showed residual disease at base of penis, so needed further surgery. How clear are the 'negative' margins/extent of surgery? My understanding is a lot of penile data is also extrapolated from vulva, and to treat the primary and nodal disease risk as separate entities. If it was close or there were any question, I would also consider post op MR if available, which can also assist with planning.

Edit/addendum: saw your additional data. Yikes.

Given the staged surgery, I would look critically in general to see whether treatment to the primary is indicated as above. Paradigm would probably be probably include in elective volume, but here I think depends really on the quality of surgery. As it's been staged surgery, I would have a very low threshold to include it in elective volumes if not just outright including it.

Agree with the dosing - 45 elective; 54 to ECE.

Has a chest CT been done?

 

[evilbooyaa]

Neoadjuvant chemotherapy for penile cancer? What the what

 

[dieABRdie]

Had a run of a few cases toward the end of residency. Without digging too much into the literature, I will share my experience:

As much as I can remember, one gentleman developed nodal recurrence (initially node negative). Dissected, adjuvant RT, developed cutaneous (field margin, thigh) and nodal in field recurrence progressing even towards the end of RT. Chalking it up to bad biology but that influenced my attending to be a lot more aggressive/in favor of adjuvant nodal treatment. He did not get chemo as your patient above.

Second patient soon after this one - partial penictomy, clear margins. Pre-treatment MRI showed residual disease at base of penis, so needed further surgery. How clear are the 'negative' margins/extent of surgery? My understanding is a lot of penile data is also extrapolated from vulva, and to treat the primary and nodal disease risk as separate entities. If it was close or there were any question, I would also consider post op MR if available, which can also assist with planning.

Edit/addendum: saw your additional data. Yikes.

Given the staged surgery, I would look critically in general to see whether treatment to the primary is indicated as above. Paradigm would probably be probably include in elective volume, but here I think depends really on the quality of surgery. As it's been staged surgery, I would have a very low threshold to include it in elective volumes if not just outright including it.

Agree with the dosing - 45 elective; 54 to ECE.

Has a chest CT been done?

Thanks for the comments.

I would agree the margins would be very helpful. Unfortunately I'm finding that pathology reports from rural areas are often "less than adequate"... sometimes shockingly so. We are either going to have the slides reviewed in house or have them sent out. What might you consider close? Extrapolating from vulva that would be 8mm. Post op MRI is a great idea as well.

So lets say I decide to treat the primary.... any comments on the best way to reproducibly immobilize this particular target? I treated a Kaposi sarcoma that was on the inferior aspect of the glans earlier this year but he had an implant and that helped. Maybe wrap it in a bolus tube?

 

[taserlaser]

Interestingly enough, there was some NAC in this series.

Contemporary Management of Penile Cancer: Greater than 15-Year MSKCC Experience

Penile cancer is a rare malignancy, and few guidelines are available to define treatment paradigms. For greater understanding of the natural history of surgically treated penile cancer, we analyzed experience at our institution.Using an institutional ...

www.ncbi.nlm.nih.gov

They had margins of about 1.0cm, however they cite some references that suggest maybe you only need a few mm... No consensus afaik.

Oh, and I typically use a patient held stockinette to keep things out of the way. For treating? I suppose you could use the same thing, and can consider and planning with some flash on the imrt plan to allow for a bit more local if planning/physics support that, but really depends how mobile the stump is. YMMV. Good luck

 

[Palex80]

Neoadjuvant chemotherapy for penile cancer? What the what

There is some data for that in patients with cN+.

 

[evilbooyaa]

There is some data for that in patients with cN+.

Interesting. Learn something new everyday.

 

[Palex80]

Adjuvant RT for penile cancer is a matter of debate. Some believe in it, some do not.

EAU-guidelines for example explicitly state that adjuvant RT has no role in penile cancer.

This is mainly driven by a review article which was recently published.

Risks and Benefits of Adjuvant Radiotherapy After Inguinal Lymphadenectomy in Node-positive Penile Cancer: A Systematic Review by the European Association of Urology Penile Cancer Guidelines Panel - PubMed

Men with penile cancer who have involvement of the inguinal lymph nodes are at a high risk of cancer recurrence and death. We reviewed the literature to see if radiation treatment after removal of the nodes provided benefit. We did not find any good-quality evidence supporting this treatment...

www.ncbi.nlm.nih.gov

I am aware that in the US adjuvant RT is often given and I full understand the biologic rationale when thinking that penile cancer grows similarly to vulvar cancer where we do have good evidence for adjuvant RT from randomized trials.

I recently worked in a group formulating guidelines for management of penile cancer and we did find consensus in recommending RT in certain cases with high risk disease.

I believe this is certainly a high risk case.

On management: Not dissecting the contralateral nodes was not a good idea. There is considerable risk of involved nodes on the contralateral side.


I would now treat bilateral nodes to at least 50 Gy and boost the involved side to 60 Gy. I do not think that going higher is supported by clear data and toxicity will be high the higher you go, we know that from anal / vulvar cancer. On the topic of chemotherapy: there is no data to point out that concurrent treatment will be favorable, one can do it, but consider the additional toxicity and the fact that the patient has already had multi-agent chemotherapy. Treating the primary site in the setting of clear margins is also not supported by data, one can do it, but it will raise toxicity.

EDIT: I would also treat pelvic nodes to 50 Gy.

 

[dieABRdie]

Thanks everyone for the responses. We talked about the patient yesterday. We basically decided to go with what Palex80 suggested. We are still getting a path review to check the margins to be sure they were adequate but will leave the primary site untouched for now.

 

[DoctwoB]

Urologist weighing in. We will sometimes use neoadjuvant chemo in the setting of cN positive disease, especially if bulky or fixed. He should have had a bilateral superficial, deep, and pelvic LND, but that has passed. We do tend to refer for adjuvant xrt in bad disease, despite limited data. Even if it doesn’t improve overall survival, the nodal control offered may keep them from eroding their femoral vessels, and may make their death a less gruesome experience.

 

[RickyScott]

have treated a few of these. Needless to say tough treatment. Make sure pt curcumcised otherwise get phimosis from xrt.

 

[evilbooyaa]

have treated a few of these. Needless to say tough treatment. Make sure pt curcumcised otherwise get phimosis from xrt.

Well he had a penectomy so I imagine that is less of a concern than you imagine.

 

[dieABRdie]

Urologist weighing in. We will sometimes use neoadjuvant chemo in the setting of cN positive disease, especially if bulky or fixed. He should have had a bilateral superficial, deep, and pelvic LND, but that has passed. We do tend to refer for adjuvant xrt in bad disease, despite limited data. Even if it doesn’t improve overall survival, the nodal control offered may keep them from eroding their femoral vessels, and may make their death a less gruesome experience.

I managed to get a hold of his original preoperative CT A/P. I believe this was the reason for the "staged" surgery. The right inguinal node was bulky and clearly would have been difficult to resect. So I presume he was hoping for the TIP chemo to facilitate nodal dissection. I scanned him Friday and he has no evidence of mets.... so maybe he still has a chance.

Thanks for the comment.