April 2017 #urojc summary: Is SABR a viable therapeutic option for managing renal tumors in patients deemed unsuitable for surgery?

In April 2017, the International Twitter-based Urology Journal Club (@iurojc) #urojc reviewed an interesting recent article by Siva et. Al reporting their experience in a prospective cohort study utilizing Stereotactic Ablative Body Radiotherapy (SABR) on inoperable primary renal cell carcinomas. The article was made freely available courtesy of BJUI for the duration of the discussion (https://onlinelibrary.wiley.com/doi/10.1111/bju.13811/full). The journal club ran for 48 hours beginning on April 2nd at 21:00 UTC. The first author of the manuscript, Dr. Shankar Siva, a radiation oncologist at the Peter MacCallum Cancer Center joined the discussion using the Twitter handle @_ShankarSiva.

The study enrolled 37 total patients (T1a n=13, T1b n=23, and T2a n=1) due to one of three reasons: (1) deemed medically inoperable (n=28 Charlson Comorbidity >6), (2) high-risk group for surgery (n=11 high risk post-surgical dialysis), (3) refused surgery (n=1). The primary outcome measured was the successful delivery of radiotherapy. Secondary outcomes included (1) adverse events of radiotherapy, (2) local progression of the disease, (3) distant progression of the disease, and (4) overall survival.

@iurojc kicked things off with a starter question

If a tumour is inoperable due to patient morbidity, should we be doing anything at all?#urojc

— Urology JC #urojc (@iurojc) April 2, 2017

There was immediate debate regarding the validity of treating patients with inoperable tumors using alternative modalities.

@iurojc This is an outdated idea from the paternalistic era of medicine. Many live long enough to suffer from untreated & preventable progression.

— Drew Moghanaki, MD (@DrewMoghanaki) April 2, 2017

@DrewMoghanaki @iurojc Neither outdated nor paternalistic. https://t.co/TfduPLDba0 @uretericbud

— Patrick Kenney (@PatrickKenneyMD) April 2, 2017

@PatrickKenneyMD cited a retrospective analysis by Kutikov et. al (@uretericbud) of the SEER database on competing causes of mortality in elderly patients with localized RCC. The study reported the 5-year probability of mortality from non-cancer related etiology to be 11% while the RCC related mortality probability was 4%. The authors of the paper encourage that management decisions for localized RCC in older patients should take into account competing causes of mortality. @DrewMoghanaki argued that many patients will still suffer from the sequelae of cancer progression that could be prevented by treating with non-surgical modalities such as SABR.
@_ShankarSiva chimed in

@DrewMoghanaki @PatrickKenneyMD @iurojc @uretericbud Similar conversation in #lungcancer a decade ago; https://t.co/dn8Mec9IBj – SABR improved OS over no Tx in elderly @drdavidpalma #urojc

— Shankar Siva (@_ShankarSiva) April 3, 2017

@uretericbud questioned the comparison of two discrepant neoplasms

@_ShankarSiva @DrewMoghanaki @PatrickKenneyMD @iurojc @drdavidpalma #urojc not sure fair comparison. kinetics of progression of localized renal masses and lung masses vastly different

— Alexander Kutikov MD (@uretericbud) April 3, 2017

@_ShankarSiva @iurojc @uretericbud @DrewMoghanaki @PatrickKenneyMD @drdavidpalma Need to know if these were ~indolent tumors in very high risk patients. If so makes the treatment look fantastic. #urojc

— David Canes (@CanesDavid) April 3, 2017

@_ShankarSiva explained

@CanesDavid @iurojc @uretericbud @DrewMoghanaki @PatrickKenneyMD @drdavidpalma Agree – we treated > 4cms, or SRMs with initial surveillance and serial growth. We had a few distant failures; so not too indolent #urojc

— Shankar Siva (@_ShankarSiva) April 3, 2017

From Belgium, an important point was made about the question itself.

@iurojc Inoperable is not the same as short life expectancy otherwise you wouldn’t even have considered surgery! RT is a valid choice for many.

— Piet Ost (@piet_ost) April 3, 2017

While this conversation was occurring, a lively discussion on the utility of SABR compared to other established non-surgical modalities was taking place.

Why SABR and not cryo or RFA? Is there a potential for greater morbidity?#urojc

— Urology JC #urojc (@iurojc) April 2, 2017

@_ShankarSiva replied

@iurojc #urojc Good question – RFA / perc cryo often limited to exophytic SRMs, away from pelvis. SABR can ‘reach’ these safely @Rad_Nation #radonc

— Shankar Siva (@_ShankarSiva) April 2, 2017

Next, @CanesDavid posed a question regarding the most frequent factors of surgical disqualification in the cohort

@_ShankarSiva @iurojc @Rad_Nation How was inoperability determined? What were the typical limiting factors? #urojc

— David Canes (@CanesDavid) April 2, 2017

@CanesDavid @iurojc @Rad_Nation Surgeons may want to comment @declangmurphy @nickbrookMD @lawrentschuk – often CVS risk factors, need for RN in solitary func kidney #urojc

— Shankar Siva (@_ShankarSiva) April 2, 2017

@benchallacombe noted a limitation of the study which led to a discussion of the utility of one of the four secondary outcomes of the study- local progression.

@_ShankarSiva @iurojc @CanesDavid @Rad_Nation @declangmurphy @nickbrookMD @lawrentschuk #urojc appears no control/comparison group here & many with t1b/t2 tumours will go 2-5 years without progression. Too early for conclusion

— Ben Challacombe (@benchallacombe) April 3, 2017

@benchallacombe @_ShankarSiva @iurojc @CanesDavid @Rad_Nation @declangmurphy @lawrentschuk I think the soft endpoint of tumour growth is a helpful endpoint in these difficult studies. Not be all and end all, but helpful #urojc

— Nick Brook (@nickbrookMD) April 3, 2017

@nickbrookMD (co-author) cited an article by Crispen et. al that characterized the growth rate of untreated solid enhancing renal masses. @Rad_Nation proposed two follow-up studies that could be conducted.

@nickbrookMD @benchallacombe @_ShankarSiva @iurojc @CanesDavid @declangmurphy @lawrentschuk So another cohort could be used to test a nomogram for local growth & ideally cancer specific survival. Then test surg v RFA v SBRT #urojc

— Radiation Nation (@Rad_Nation) April 3, 2017

Even if these studies are conducted, there is skepticism around whether Urologists will view SBRT as a viable alternative treatment modality for RCC.

@Rad_Nation @benchallacombe @_ShankarSiva @iurojc @CanesDavid @declangmurphy @lawrentschuk I think surgeons won’t see SABR as another ‘option’ – rather a fall back when surgery doesn’t make sense #urojc

— Nick Brook (@nickbrookMD) April 3, 2017

@nickbrookMD @Rad_Nation @benchallacombe @_ShankarSiva @iurojc @CanesDavid @declangmurphy @lawrentschuk With change in age and comorbidity this will change I think. #prostatecancer had #EBRT “only” a long time. #urojc

— Alfred Honoré (@diamias) April 3, 2017

@iurojc posed an important question. What should be the overall goal of the urologist? Is it to cure cancer by all means? Or perhaps to find a balance between quality of life and management of the disease? SBRT may play a crucial role in the latter situation.

Putting aside comorbidity, what do you consider to be any factors that could make a renal tumour unsuitable for surgery? #urojc

— Urology JC #urojc (@iurojc) April 3, 2017

@iurojc If one prioritizes oncologic goal over function, there is no true inoperable tumor (if you can accept renal failure/dialysis as okay) #urojc

— David Y.T. Chen (@dytcmd) April 3, 2017

@iurojc Single kidney in a patient who doesnt want dialysis? #urojc

— Alfred Honoré (@diamias) April 3, 2017

To wrap things up, @iurojc asked a summary question.

What’s the next step to convince widespread use of SABR for renal tumours? Or are you sufficiently convinced? #urojc

— Urology JC #urojc (@iurojc) April 4, 2017

The authors of the manuscript provided a response and their thoughts on what needs to be done next.

@iurojc Role is in pts medically (incl sCKD) high risk for surgery with large and growing mass – in whom modern meds r extending life expec #urojc

— Nick Brook (@nickbrookMD) April 4, 2017

@nickbrookMD @iurojc Need more trials – this one might help https://t.co/T19jSnCeaM @lawrentschuk @DocJarad @Prof_IanD @ANZUPtrials @TROGfightcancer #urojc

— Shankar Siva (@_ShankarSiva) April 4, 2017

Thank you to everyone who participated in the April 2017 #urojc. Special thanks to the authors @_ShankarSiva and @nickbrookMD for joining in on the discussion and providing further insight to their work.

Akhil Saji is a third-year medical student at New York Medical College, Valhalla, NY.

Twitter @AkhilASaji

References

1. Siva, Shankar, et al. “Stereotactic ablative body radiotherapy for inoperable primary kidney cancer: a prospective clinical trial.” BJU international (2017)

2. Kutikov, Alexander, et al. “Evaluating overall survival and competing risks of death in patients with localized renal cell carcinoma using a comprehensive nomogram.” Journal of Clinical Oncology 28.2 (2009): 311-317.

3. Crispen, Paul L., et al. “Predicting growth of solid renal masses under active surveillance.” Urologic Oncology: Seminars and Original Investigations. Vol. 26. No. 5. Elsevier, 2008