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.

14th Annual California Cancer Conference Consortium

August 10-12, 2018

Challenging Case #2:

Genitourinary Cancer

Mamta Parikh,MD,MS

UC Davis Comprehensive Cancer Center

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

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

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

Staging

• Post-op PSA: 23

• Received 30 Gy RT in 10 fractions to right sphenoid wing

• Then presented for further treatment options

Treatment Options for Newly Diagnosed Metastatic Prostate Cancer

• Options:

– Androgen Deprivation Therapy (ADT)

– ADT + docetaxel for 6 cycles

– ADT + abiraterone plus prednisone

Docetaxel benefit in high volume metastatic disease

E3805 CHAARTED trial

CE Kyriakopoulos et al, J Clin Oncology 2018

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

Case continued

• Treated with leuprolide with abiraterone + prednisone

– PSA nadir: 1.12 (at 3 months of treatment)

– PSA at 6 months: 10.38

• Repeat PSA 1 week later: 23.9

• Testosterone appropriately suppressed

– Pain in right arm

• Early PSA progression correlates to poor prognosis

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)

Options for treatment of newly diagnosed mCRPC

• Docetaxel + prednisone

• Abiraterone + prednisone

• Enzalutamide

• Radium-223

• Sipuleucel-T

Clinical Course

• Completed 6 cycles of docetaxel + prednisone

– PSA from 23.9 0.7

– 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

Visceral progression 2 months after docetaxel

Liver biopsy

• Poorly differentiated neuroendocrine carcinoma

– Synaptophysin positive

– Chromogranin positive

– PSA negative

– Ki67 high

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

Management of t-SCNC

• Extrapolated largely from small cell lung cancer experience

• Platinum-based chemotherapy often used first-line

– Carboplatin + docetaxel

– Carboplatin/cisplatin + etoposide

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

Other testing

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

Clinical Course

• Did not tolerate trial of irinotecan

– Cytopenias

– Nausea/vomiting

– Worsening performance status

• Patient declined further treatment, opted for hospice

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

Questions?