MAMTA PARIKH, MD, MS CHALLENGING CASE #2: GU CANCER & STATE OF THE ART: CASTRATION RESISTANT PROSTATE CANCER

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1 MAMTA PARIKH, MD, MS CHALLENGING CASE #2: GU CANCER & STATE OF THE ART: CASTRATION RESISTANT PROSTATE CANCER NO RELEVANT FINANCIAL RELATIONSHIPS IN THE PAST TWELVE MONTHS BY PRESENTER OR SPOUSE/PARTNER. THE SPEAKER WILL DIRECTLY DISCLOSURE THE USE OF PRODUCTS FOR WHICH ARE NOT LABELED (E.G., OFF LABEL USE) OR IF THE PRODUCT IS STILL INVESTIGATIONAL. 14 th Annual California Cancer Conference Consortium August 10-12, 2018

2 Challenging Case #2: Genitourinary Cancer Mamta Parikh,MD,MS UC Davis Comprehensive Cancer Center

3 Patient Case 74 year old man with epiphora Past Medical History T1 urothelial carcinoma at age 63 s/p TURBT and subsequent cystoscopic surveillance Diagnosed with Gleason 4+3 prostate adenocarcinoma at age 66 Treated with EBRT with undetectable PSA subsequently until ~3 years ago Social History: 25 pack year smoking history Family History: negative for malignancies

4 HPI Developed LUTS after EBRT, which was stable Developed tearing of the right eye MRI brain benign Given eye drops (Restasis) Then pain, ptosis and diplopia of the right eye 1 month later Numbness/tingling on the right side of face Had not undergone cystoscopy in 1 year PSA increasing gradually to 9 over last 3 years, no recent doubling Repeat MRI showed a right sphenoid wing mass consistent with meningioma

5 Subsequent findings Right frontotemporal craniotomy, resection of tumor from orbital bone and sphenoid wing- unable to safely resect all tumor Pathology: metastatic poorly differentiated adenocarcinoma of prostate

6 Staging Post-op PSA: 23 Received 30 Gy RT in 10 fractions to right sphenoid wing Then presented for further treatment options

7 Treatment Options for Newly Diagnosed Metastatic Prostate Cancer Options: Androgen Deprivation Therapy (ADT) ADT + docetaxel for 6 cycles ADT + abiraterone plus prednisone

8 Docetaxel benefit in high volume metastatic disease E3805 CHAARTED trial CE Kyriakopoulos et al, J Clin Oncology 2018

9 Abiraterone + prednisone benefit in hormone-sensitive prostate cancer STAMPEDE LATITUDE ND James et al. N Engl J Med 2017 K Fizazi et al. N Engl J Med 2017

10 Case continued Treated with leuprolide with abiraterone + prednisone PSA nadir: 1.12 (at 3 months of treatment) PSA at 6 months: Repeat PSA 1 week later: 23.9 Testosterone appropriately suppressed Pain in right arm Early PSA progression correlates to poor prognosis

11 Onset of Castration Resistant Prostate Cancer Radiographic progression with increased size of right humerus metastasis, new rib and spinal mets RT to R humerus (30 Gy in 10 fractions)

12 Options for treatment of newly diagnosed mcrpc Docetaxel + prednisone Abiraterone + prednisone Enzalutamide Radium-223 Sipuleucel-T

13 Clinical Course Completed 6 cycles of docetaxel + prednisone PSA from Discontinued due to Grade 2 peripheral neuropathy Continued on ADT + monthly denosumab alone 2 months later, PSA 2.8 And new onset right-sided swelling on the face and fatigue

14 Visceral progression 2 months after docetaxel

15 Liver biopsy Poorly differentiated neuroendocrine carcinoma Synaptophysin positive Chromogranin positive PSA negative Ki67 high

16 Neuroendocrine Small Cell Prostate Cancer Can occur de novo or with progression of mcrpc Primary prostatic small cell carcinoma (de novo) quite rare (~0.5 2% of all cases of prostate cancer at diagnosis) Progression of mcrpc (t-scnc)- Has been reported in 10-20% of autopsy specimens in patients who died of mcrpc Often low-psa producing or with mcrpc, discordance of progression with extent of PSA increase

17 Management of t-scnc Extrapolated largely from small cell lung cancer experience Platinum-based chemotherapy often used firstline Carboplatin + docetaxel Carboplatin/cisplatin + etoposide

18 Continued Clinical Course Carboplatin and etoposide x 4 cycles PSA decreased to 0.2 Decrease in hepatic metastases, retroperitoneal adenopathy and pulmonary nodules Completed total of carboplatin and etoposide x 6 cycles PSA stable at 0.2

19 Other testing Next-generation sequencing PTEN Y68H TP53 A138V RB1 loss exons 7-20 MSI-stable TMB-low PD-L1 <1%

20 Clinical Course Did not tolerate trial of irinotecan Cytopenias Nausea/vomiting Worsening performance status Patient declined further treatment, opted for hospice

21 Key Points PSA kinetics at 7 months with newly diagnosed metastatic prostate cancer is prognostic Small increases in PSA with significant progression should prompt a biopsy/suspicion for t-scnc Like small cell lung cancer, t-scnc is responsive to platinum-based therapies but eventually recur/progress May be a role for immunotherapy

22 Questions?