CUA 2018: Management of the Low Volume (1cm) Post-chemotherapy NSGCT Retroperitoneal Mass

Halifax, Nova Scotia ( 37 year old man, healthy, married with 2 kids, found to have a left testicular mass. Orchiectomy: pT3, +LVI, Rete+, Spermatic cord + (90% embryonal, 10% chorio). Post-orchiectomy his tumor markers remained elevated. Staging scans with 4.5 cm solitary left para-aortic LN. As he is good risk, he undergoes BEP x 3. Post-chemotherapy, his staging studies demonstrate a 0.9 cm left para-aortic node.

His options include:
1) Post-chemotherapy RPLND
2) Salvage chemotherapy
3) Radiation
4) Surveillance
Realistically, it is #1 and #4 that are the best options.

We had two excellent testicular cancer experts debate in favor of each treatment option.

PRESENTER #1: Robert Hamilton
INSTITUTION(S): Princess Margaret Cancer Centre, University of Toronto, Toronto, ON

Dr. Hamilton went first in support of surveillance.
As background, he some ground rules/assumptions that both would agree with:
1. A properly executed RPLND is a critical factor for NSGCT cure – particularly post-chemotherapy
2. Key post-chemo mass histology – teratoma (can grow or transform) and chemorefractory viable tumor must be removed
3. The challenge is knowing when those elements are present!
- 40-50% of the time, this post-chemo mass will be fibrosis/scar
- We know that smaller masses are more likely to be fibrosis/scar
- “Complete Response” (CR) – is defined as normal tumor markers and RP mass diameter < 1.0 cm
- Most groups advocate for surveillance in this setting because:
- Chance of necrosis/fibrosis is high
- PC-RPLND is morbid
- He will argue that overall survival (OS) is the same!

“Can we do less and achieve the same”? This is the Canadian way – and we have already adopted this for prostate cancer, CS1 TCa, and kidney cancer! Same paradigm applies here.

1. 1 cm cutoff – if the cutoff was 0 cm (true negative), then we would be doing too many PC-RPLNDs. If the cutoff was higher, then we would likely be doing too few. Many feel 1 cm is appropriate cutoff.
2. PC-RPLND histology distribution has changed over time!
- Original rule of “40-40-20” is now outdated
- Most recent series, including MSKCC and PMH, demonstrate that only about 5-7% of PC-RPLND mass histology is viable tumor; teratoma is approximately 20-25%. Between the two, histology that requires excision is around 30-35% - which means ~2/3 do not need excision!
3. Morbidity of PC-RPLND is not minimal
- Historical series, 18% risk of major complications (Baniel et al JUrol 1995)
- More recent series, 10% Grade 3-5 complication rate (Subramanian Urol Onc 2010)
- Morbidity due to desmoplastic reaction to chemotherapy, which may be even worse in small masses (more chemo response!) – amongst other things

I particularly like this point from Dr. Hamilton:

CUA image 2

Patients undergoing PC-RPLND for subcentimeter masses still have a 2-3% 5-year relapse rate (and these are usually outside the retroperitoneum)
Patients undergoing surveillance have a 5% 5-year relapse rate – but 60% of these are in the retroperitoneum. And an RPLND can be done at this time.
Therefore, the extra-peritoneal relapse rate is approximately the same – but you save some patients an unnecessary operation!

In terms of survival, he reported the PMH data – of 169 patients, 7.7% relapses on surveillance. All that underwent surgery were cured – no further relapses to-date. Patients with mixed relapse (including outside the RP) did worse – 3 patients died (1.8%).

His take-home points:

CUA image 2b

He briefly touched on clinical and novel markers that may be able to better predict the patients that need intervention – yet, these still need to be validated.

PRESENTER #2: Joel Sheinfeld
INSTITUTION: Memorial Sloan Kettering Cancer Centre, NYC, New York, USA

Dr. Sheinfeld followed with an argument to do a PC-RPLND in these patients.

He started off by saying the balance in medicine has always been a balance between overtreatment (excess morbidity, unnecessary cost) and undertreatment (increased risk, increased relapse, worse clinical outcome). It is a zero-sum game – risk of undertreatment increases as overtreatment decreases. Unfortunately, undertreatment often harms the favorable risk patient that had a chance at cure.

He had a few key counter points and arguments for why surveillance may not be the best option.

1. A “negative” PC-RPLND may still have therapeutic benefit – if the final pathology is fibrosis/scar, considered a negative PC-RPLND. Yet, interesting in desperation RPLND’s, even in this setting, 90% of patients had resolution of tumor markers – suggesting that pathologists may just be missing viable disease (Indiana data)
- The more extensive a negative PC-RPLND, the less the likelihood of relapse (MSKCC data)

2. Residual <1 cm node – 30-35% even in modern series have either teratoma or viable tumor. While viable tumor may only be 5-7%, even a small amount of teratoma is concerning and needs to be removed. Unfortunately, the biology of teratoma is unpredictable.

3. Potential consequences of small untreated viable tumors? Relapse and late relapse. But, does timely intervention at the time of relapse provide equivalent outcomes compared to early PC-RPLND?
- Ehrlich Y JCO 2010 – in subcentimeter masses with long-term (15+ year) follow-up, 12 patients had relapses, and 5 patients had late relapses. 4 men died of disease (3%). Median age at the end of follow-up was ~42 – so patients still have another 40+ years to develop relapses.
- In the MSKCC experience, 0 patients have died
- Hendry Cancer 2002 demonstrated that salvage RPLND patients have worse RFS and OS than early RPLND – yet there is inherent selection bias here

4. Full bilateral template is warranted in these patients. In addition, they are able to achieve good antegrade ejaculation in this population (<2 cm mass, 83% antegrade ejaculation rate).

His take-home points:

CUA image 2c

Presented by: Peter Black, MD, University of British Columbia, Vancouver, BC

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 73rd Canadian Urological Association Annual Meeting - June 23 - 26, 2018 - Halifax, Nova Scotia