Old and New Radiation for Bladder and Upper Tract Cancers. Bridget Koontz Radiation Oncology Duke Cancer Institute

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1 Old and New Radiation for Bladder and Upper Tract Cancers Bridget Koontz Radiation Oncology Duke Cancer Institute

2 Disclosures Janssen funded clinical research BlueEarth Diagnostics advisory board member

3 Agenda Bladder Preservation what s new? Upper Tract and Renal Cell Cancer SBRT for oligometastases

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5 Audience Poll How many routinely offer bladder preservation? If not why? Don t see MIBC Cystectomy is better CRT has too much toxicity CRT criteria too restrictive

6 MIBC: AUA/ASCO/ASTRO/SUO Guideline For patients with newly diagnosed non-metastatic MIBC who desire to retain their bladder and for those with significant comorbidities for whom radical cystectomy is not a treatment option, clinicians should offer bladder preserving therapy when clinically appropriate. (Clinical Principle) A multi-modal bladder preserving approach with its merits and disadvantages should be discussed in each individual case. Chang J Urol. 2017;198(3):552.

7 History of Radiation for Bladder Cancer 1960s: cystectomy alone disappointing 1960s/1970s: definitive RT not effective 1970s: PRE-OP RT (Whittmore MSKCC) gratifyingly improved RCT showed no benefit 1980s: chemotherapy reduced systemic failures 1980s: MGH subset analysis showed improvement in papillary tumors, complete resection Cummings Semin Oncol 1979; 6:220. Shipley J Urol 1985:134:679.

8 Bladder Preservation Trials Jani Hem Onc Clin NA 2015; 29:289.

9 SPARE Trial RC vs RT for MIBC multicentre phase III randomised controlled trial with an initial feasibility study for accrual UK NHS study Adult patients with T2 T3 N0 M0 TCC of the bladder and normal kidney/heme function (No HN, upper tract disease) Gem/Cis x 2, then randomized to radical cystectomy versus bladder preservation Huddart BJU Int Nov;120(5): This was RT ALONE after 2 cycles gem/cis, NOT US standard of care

10 SPARE Trial RC vs RT for MIBC Radical Cystectomy 25 Bladder Preservation 20 Huddart BJU Int Nov;120(5):639.

11 SPARE Trial RC vs RT for MIBC Huddart BJU Int Nov;120(5):639.

12 SPARE Trial RC vs RT for MIBC Huddart BJU Int Nov;120(5):639.

13 SPARE Trial RC vs RT for MIBC P=.13 Huddart BJU Int Nov;120(5):639.

14 SPARE Trial RC vs RT for MIBC In chemotherapy responders: Due to the small number of patients, firm conclusions about disease and toxicity outcomes following these interventions cannot be drawn, although high rates of bladder preservation appear to be achievable in chemotherapy responders without compromising OS. Strong clinician and patient preferences for treatments impacted willingness to undergo randomisation and acceptance of treatment allocation. Huddart BJU Int Nov;120(5):639.

15 Meta-Analysis comparing RC/CRT 10 year Overall Survival Vashistha IJROBP 2017 Apr 1;97(5):1002.

16 Meta-Analysis comparing RC/CRT 10 year Disease-Specific Mortality Vashistha IJROBP 2017 Apr 1;97(5):1002.

17 Quality of Life with CRT 173 patients at MGH/DFCI Adults with MIBC treated with either RC or BPT between Disease free for at least 2 years Prospective QOL questionnaires: EORTC QLQ-C30 EORTC MIBC (QLC-BLM30) and bowel (EPIC) EuroQOL EQ-5D Mak IJROBP 2016;96(5):1028.

18 Quality of Life with CRT Mak IJROBP 2016;96(5):1028.

19 Quality of Life with CRT Mak IJROBP 2016;96(5):1028.

20 Real World Bladder Preservation Those choosing bladder preservation OR Those inappropriate for radical cystectomy Maximize TURBT Don t do RT alone purely palliative Chemo choices: CDDP, MMC/5FU, or gemcitabine

21 Alternative Regimens Gemcitabine / Cisplatin Caffo Cancer 2011;117: patients; CCDP d1, 22; Gem weekly 5yo OS 70%; IBS 74% MMC / 5FU BC2001 James N Engl J Med 2012; 366: patients; MMC d1, bolus 5FU d 1, 16 2y DFS 67%

22 Kalbasi J Clin Invest. 2013;123(7):2756. New Directions Radiation can increase antigen presentation and pro-inflammatory cytokines

23 Upcoming SWOG/NRG Trial Bladder Preservation +/- Atezolizumab ct2-t4a muscle invasive urothelial ca No severe hydronephrosis All three chemo regimens allowed Once daily, no TURBT halfway through

24 Radiation for Upper Tract Ca UpToDate There is no role Localized surgery Metastatic chemo / immunotherapy Where can radiotherapy benefit?

25 SBRT for RCC mets SD = 18, 20, 22, or 24 Gy x 1; Hypofrac = 6 x 5 or 8 x 3 Zelefsky IJROBP 2012:1744.

26 Preclinical Evidence - RCC Park Cancer Immunol Res

27 Evaluation of RT with PD1 Inhibition Sundahl J Transl Med 2017 Jun 29;15(1):150.

28 SBRT for Limited Metastases/Unresectable Solitary Adrenal or LN Metastasis 59yo man diagnosed with RCC 2007 Recurrent with R adrenalectomy 2009 Pulm mets since 2013 on sunitinib, then cabozantinib, then nivolumab 35 Gy / fractions left adrenal 9 months, stable/decreasing lesions Distal Ureter: 87yo man with occult hematuria and ct2n0 tumor at the distal one-third of the left ureter with dilation of the upper ureter and ipsilateral renal pelvis 50 Gy / 10 fractions 12mo LC Died 13mo Maehata Case Rep Urol. 2015;2015:

29 Summary Bladder preservation is real world option for those who prefer to keep bladder or are not good cystectomy options Radiation is being evaluated in combination with immune checkpoint inhibitors for both primary MIBC and urothelial metastases SBRT is an option for oligomets, local control is high