nodal relapse 9y after RP and PORT for prostatic carcinoma

[Kroll2013]

75 years old patient, with controlled diabetes and hypertension, very fit.
he underwent in 2009, a radical prostatectomy followed 30 fractions of adjuvant 3D conformal radiation therapy to the prostatic bed only.
in 2018: PSA rise to 2.16
2019: PSA 2.16

Pet PSMA showed a 7 mm LN at the level of L4-5 secondary lesion, with no recurrence in the tumor bed, neither in bone or other LNs.
He was put on decapeptyl + casodex.

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[TomatoMan]

I treated pelvis & PA nodes + SIB to gross disease w/ ST-ADT in 2 similar patients. Both did well with undetectable PSA for several years, but one of them recently had a PSA relapse and I just ordered an Axumin scan on him.

 

[Mandelin Rain]

I'd vote node only, rationale being other nodes have had 10years yo declare themselves.

 

[ramsesthenice]

I treated pelvis & PA nodes + SIB to gross disease w/ ST-ADT in 2 similar patients. Both did well with undetectable PSA for several years, but one of them recently had a PSA relapse and I just ordered an Axumin scan on him.

One could use your experience to argue against comprehensive nodal RT in this setting. I do SBRT only for very well-selected patients (like this guy) with very favorable prognostic features and about 1/3 remain NED for at least 18-24 months with no ADT. That really isn’t much worse than my experience with conventional fractionation and fields. Of course, what we really need are good trials to try to answer this question. Until then, it’s all about consent and good communication with the patient. SBRT will be less toxic but it’s not the current SOC. Since we have a good bio marker for CSPCa it’s reasonable to try but if they want to do things by the book or be as aggressive as possible then it’s conventional all they way.

 

[mavrik13]

Pelvis + paraaortics (would treat 1 full vertebral body height above positive node) to 45/25 with SIB to 60/25 or small bowel tolerance. Would give 2-3 years ADT along with it. Could easily make an argument for SBRT. This is an area we need to have a trial.

 

[Mandelin Rain]

As for a trial.... in greater than 10 years doing this, I’m not sure I’ve seen more than 1 isolated solitary nodal recurrence in previously untreated pelvis prostate cancer. I’d think that trial would be slow to accrue.

 

[Palex80]

PEACE V (STORM) is randomizing patients in exact this scenario to:

a) lymph node only RT / salvage surgery
vs.
b) elective whole pelvis RT + focal boost / surgery

I've actually seen quite a few of these patients. Especially now when we use PSMA-PET-CT to pick them up early on.

Here's STORM:

ClinicalTrials.gov

clinicaltrials.gov

 

[Mandelin Rain]

PEACE V (STORM) is randomizing patients in exact this scenario to:

a) lymph node only RT / salvage surgery
vs.
b) elective whole pelvis RT + focal boost / surgery

I've actually see quite a few of these patients. Especially now when we use PSMA-PET-CT to pick them up early on.

Good to know. Maybe this is a more common scenario than I've given credit for.

 

[BobbyHeenan]

I've struggled with these too.

I used to think the newer imaging (PSMA/Axumin) was so good it may be OK to just treat the node with SBRT with 6-18 months ADT but I'm starting to think maybe more comprehensive nodal approach is better in retrospect on some patients I've been faced with in the past.

With a 9 year interval I'm very reluctantly voting SBRT. My last guy in this situation had about a 4 year interval between prostatectomy and PSA relapse/Axumin detection. I did SBRT plus 3 months ADT (he was like 80 years old). 2 years PSA recurrence free but now PSA back at around 0.5. OBviously, we're not going to do anything unless it shows up on scans.

 

[Palex80]

Here's a case I can share with you

03/2016: radical prostatectomy pT3b pN0 (0/5) Pn1 R1 GS 5+4=9, preOP PSA 13.7 ng/ml
06/2016: adjuvant RT to the prostatic fossa 66/2 (RT started at undetectable PSA-level)
02/2018: PSA-rise 0.6 ng/ml --> PSMA-PET-CT: solitary avid lymph node internal iliac vessels riight
04/2018: salvage lymphadenectomy --> pN1 (1/4)
06/2019: postOP-PSA: 0.1 ng/ml
08/2018: postoperative ("adjuvant") RT of the pelvis (excluding the prostatic fossa which was already treated) 50.4/1.8
10/2018: PSA-stable/drops to 0.05 ng/ml
07/2019: PSA-rise 0.5 ng/ml --> PSMA-PET-CT: solitary avid lymph node internal iliac vessels right (a few cms more cranial than the one 02/2018, still well within the treated volume of 08/2018)
10/2019: SBRT (I know you only call SBRT something with up to 6 fractions in the US...) of the node 10 x 6 Gy (10 x 4 Gy to 60% isodose)
12/2019: PSA-drops to 0.2 ng/ml


Still no ADT given (the patient refused to have any, I would have liked to give some when treating the lymphatics)

 

[Mandelin Rain]

Here's a case I can share with you

03/2016: radical prostatectomy pT3b pN0 (0/5) Pn1 R1 GS 5+4=9, preOP PSA 13.7 ng/ml
06/2016: adjuvant RT to the prostatic fossa 66/2 (RT started at undetectable PSA-level)
02/2018: PSA-rise 0.6 ng/ml --> PSMA-PET-CT: solitary avid lymph node internal iliac vessels riight
04/2018: salvage lymphadenectomy --> pN1 (1/4)
06/2019: postOP-PSA: 0.1 ng/ml
08/2018: postoperative ("adjuvant") RT of the pelvis (excluding the prostatic fossa which was already treated) 50.4/1.8
10/2018: PSA-stable/drops to 0.05 ng/ml
07/2019: PSA-rise 0.5 ng/ml --> PSMA-PET-CT: solitary avid lymph node internal iliac vessels right (a few cms more cranial than the one 02/2018, still well within the treated volume of 08/2018)
10/2019: SBRT (I know you only call SBRT something with up to 6 fractions in the US...) of the node 10 x 6 Gy (10 x 4 Gy to 60% isodose)
12/2019: PSA-drops to 0.2 ng/ml


Still no ADT given (the patient refused to have any, I would have liked to give some when treating the lymphatics)

I guess I'm not seeing value in treating the larger field in this example, and is kind of what I'd expect to happen. It just ended up complicating the subsequent radiation. With Gleason 9 disease I'd likely limit my field even more because of the increased risk of occult distant mets.

 

[Palex80]

I guess I'm not seeing value in treating the larger field in this example, and is kind of what I'd expect to happen. It just ended up complicating the subsequent radiation. With Gleason 9 disease I'd likely limit my field even more because of the increased risk of occult distant mets.

On the other hand, I think this case represents a nice example of "What If" I had treated him 2016 with elective pelvic radiation ) and added some ADT on top (as in RTOG 0534.
The main limitation of course is that I treated him in the adjuvant scenario with an undetectable PSA and not in the salvage setting (as in RTOG 0534).
His PSA was undetectable in 2016 and he was ready to undergo treatment 3 months post-prostatectomy. What if I had to wait 1-2 months longer (for example if he had some issues with urinary incontinence) and he had a slowly rising PSA of 0.15 ng/ml prior to the planned adjuvant RT. Should I call it "early salvage", add lymphatics (he only had 5 nodes dissected!) and some ADT (he would have probably still refused that)?

And maybe that would have cured him and he wouldn't have needed any further treatment down the road?

 

[ramsesthenice]

On the other hand, I think this case represents a nice example of "What If" I had treated him 2016 with elective pelvic radiation ) and added some ADT on top (as in RTOG 0534.
The main limitation of course is that I treated him in the adjuvant scenario with an undetectable PSA and not in the salvage setting (as in RTOG 0534).
His PSA was undetectable in 2016 and he was ready to undergo treatment 3 months post-prostatectomy. What if I had to wait 1-2 months longer (for example if he had some issues with urinary incontinence) and he had a slowly rising PSA of 0.15 ng/ml prior to the planned adjuvant RT. Should I call it "early salvage", add lymphatics (he only had 5 nodes dissected!) and some ADT (he would have probably still refused that)?

And maybe that would have cured him and he wouldn't have needed any further treatment down the road?

All reasonable thoughts. Another possibility though is that 50.4 isn’t that good at controlling microscopic disease in prostate cancer. It’s a reasonable though considering how hard it has been to conclusively show a benefit for ENI prostate cancer in any setting.

 

[Mandelin Rain]

All reasonable thoughts. Another possibility though is that 50.4 isn’t that good at controlling microscopic disease in prostate cancer. It’s a reasonable though considering how hard it has been to conclusively show a benefit for ENI prostate cancer in any setting.

This has always been my thought. 5040cGy probably just doesn't do it. Otherwise, we'd probably have SOME decent evidence of ENI.

 

[evilbooyaa]

There's data for better control with comprehensive LN coverage. Can't find link now but Beriwal linked to it in a relatively recent med net post.

 

[Palex80]

There's data for better control with comprehensive LN coverage. Can't find link now but Beriwal linked to it in a relatively recent med net post.

We do have that old RTOG9413 sub-group analysis of mini-pelvis vs. whole-pelvis.

Whole-pelvis, "mini-pelvis," or prostate-only external beam radiotherapy after neoadjuvant and concurrent hormonal therapy in patients treated in the Radiation Therapy Oncology Group 9413 trial - PubMed

This subset analysis demonstrates that RT field size has a major impact on PFS, and the findings support comprehensive nodal treatment in patients with a risk of LN involvement of > 15%.

www.ncbi.nlm.nih.gov

 

[Mandelin Rain]

We do have that old RTOG9413 sub-group analysis of mini-pelvis vs. whole-pelvis.

Whole-pelvis, "mini-pelvis," or prostate-only external beam radiotherapy after neoadjuvant and concurrent hormonal therapy in patients treated in the Radiation Therapy Oncology Group 9413 trial - PubMed

This subset analysis demonstrates that RT field size has a major impact on PFS, and the findings support comprehensive nodal treatment in patients with a risk of LN involvement of > 15%.

www.ncbi.nlm.nih.gov

I mean, that was before daily image guidance and even routine CT sim. Sometimes having a bigger field just meant you were actually hitting the target organ each day.

Also, the actual, randomized evidence showed that the prostate only arm with adjuvant ADT had the best PFS.

I'm not saying that Roach would outright lie in a published article, but I'm sure that unplanned sub-group data has been "massaged" quite a bit. Looking at the "real data", there is literally no way the pelvic RT group had twice the PFS as the prostate only group, at any point, on any subset analysis without significant "massaging". Ignoring the whole, pelvis vs mini pelvis issue, you can certainly see that the median PFS for the prostate only group was not 2.9 years as quoted in the linked subset analysis.

 

[Burt Radnolds]

Current body of evidence suggests more comprehensive coverage better but SBRT cherry picking a viable strategy as well.

https://www.europeanurology.com/article/S0302-2838(19)30533-0/fulltext

Salvage Stereotactic Body Radiotherapy for Isolated Lymph Node Recurrent Prostate Cancer: Single Institution Series of 94 Consecutive Patients and 124 Lymph Nodes - PubMed

SBRT is safe and offers good in-field control. At 2 years after SBRT, 1 of 3 patients is progression-free. Further investigation is warranted to identify patients who benefit most from SBRT and to define the optimal combination with AD.

www.ncbi.nlm.nih.gov

 

[evilbooyaa]

There's data for better control with comprehensive LN coverage. Can't find link now but Beriwal linked to it in a relatively recent med net post.

Link:

Metastasis-directed Therapy in Treating Nodal Oligorecurrent Prostate Cancer: A Multi-institutional Analysis Comparing the Outcome and Toxicity of Stereotactic Body Radiotherapy and Elective Nodal Radiotherapy - PubMed

This study investigated the difference between stereotactic and elective nodal radiotherapy in treating limited nodal metastatic prostate cancer. Nodal relapse was less frequent following elective nodal radiotherapy than following stereotactic body radiotherapy, and thus elective nodal...

www.ncbi.nlm.nih.gov

Differences in ADT use between the two groups muddies the results, BUT:

Elective nodal RT with SIB to involved LNs had lower nodal recurrence rate than those getting SBRT, especially in those with only one LN positive. Downside is a 3-fold higher rate of toxicity (16 vs 5%) with elective nodal RT.

Oh, this is the same first link @radmonckey provided above.

Here's the mednet discussion for reference: theMednet - Login

 

[ramsesthenice]

Link:

Metastasis-directed Therapy in Treating Nodal Oligorecurrent Prostate Cancer: A Multi-institutional Analysis Comparing the Outcome and Toxicity of Stereotactic Body Radiotherapy and Elective Nodal Radiotherapy - PubMed

This study investigated the difference between stereotactic and elective nodal radiotherapy in treating limited nodal metastatic prostate cancer. Nodal relapse was less frequent following elective nodal radiotherapy than following stereotactic body radiotherapy, and thus elective nodal...

www.ncbi.nlm.nih.gov

Differences in ADT use between the two groups muddies the results, BUT:

Elective nodal RT with SIB to involved LNs had lower nodal recurrence rate than those getting SBRT, especially in those with only one LN positive. Downside is a 3-fold higher rate of toxicity (16 vs 5%) with elective nodal RT.

Oh, this is the same first link @radmonckey provided above.

Here's the mednet discussion for reference: theMednet - Login

This is one where OS really is what matters. Ok, so ENI might (and more ADT mind you) might get you longer bPFS. But does it change the disease course compared to repeat SBRT at progression? If it turns out the answer is no, then it becomes harder to justify the added toxicity. We need more data with the right end points.

 

[PhotonBomb]

Then again if you look at the toxicity data from 0534, adding elective pelvis added very very minimal toxicity

 

[ramsesthenice]

Then again if you look at the toxicity data from 0534, adding elective pelvis added very very minimal toxicity

sorry, but no. The difference in toxicity between 4 fraction SBRT to a single node and comprehensive pelvic RT is not minimal. I am by no means suggesting that comprehensive salvage RT is unacceptably toxic, but most patients getting single site SBRT have literally no detectable toxicity.

 

[PhotonBomb]

sorry, but no. The difference in toxicity between 4 fraction SBRT to a single node and comprehensive pelvic RT is not minimal. I am by no means suggesting that comprehensive salvage RT is unacceptably toxic, but most patients getting single site SBRT have literally no detectable toxicity.

I’m just saying that looking at the data it’s pretty minimal with prospectively collected modern IMRT data.