Treating mHSPCa or mCRPC in a Community Setting

Jorge Garcia, MD:Owning the patient doesn’t really matter that much. I think that understanding the importance of a multidisciplinary approach is the key to success here. In my institution [Cleveland Clinic], none of us has a lot of ego in the sense that it’s my patient and I just send them to you when the patient needs chemotherapy. I think men with metastatic hormone-sensitive disease may require urology, may need radiation oncology, and will need a medical oncologist.

If you have metastatic low-volume disease and you happen to have your primary prostate in place, the standard of care, in my opinion today, with the STAMPEDE data, with other pieces of data, would indicate that you want to put that patient on your best systemic therapy. At this stage of the game, in my opinion, that would be suppression of testosterone in addition to abiraterone acetate and prednisone; and you should consider treating their primary tumor. As STAMPEDE clearly has suggested, the men with low-volume metastatic disease who get intensified with ADT [androgen deprivation therapy] and abiraterone may in fact have a survival improvement when you give radiation therapy to a primary tumor.

That data were actually looking at ADT, chemotherapy, and radiation against ADT and chemotherapy. But since we believe ADT and chemotherapy tend to be very similar in nature, if I’m allowed to use that expression, compared with ADT and abiraterone for that patient population, I think that the consideration of radiation therapy for those men with low-volume disease is key. The field is changing drastically.

There is a lot of movement in trying to actually even subset patients with low-volume disease into what we call oligometastatic disease.Oligo, obviously from the Latin root, means “small” or “little.” So I think the bigger question is, how do we define oligometastatic disease? Is it 1 lesion, 2 lesions, or 3 lesions? Those patients do have metastatic disease, but we may be able to render them free of disease if we intensify their therapy. So now we’re talking about maybe the potential of actually getting intensification of your systemic therapy, radiating your primary tumor, and for that matter, considering radiation therapy approaches to sites of disease that are outside the pelvic area or in the bony structures.

For castration-resistant disease, I think that it is an oncological-driven approach, obviously. I recognize that the market has changed, and there’s a lot of interest from some specialty groups, especially within the urology practices in America, to use oral therapies such as abiraterone, enzalutamide, and maybe darolutamide if it gets approved. But the reality of it is, again, I continue to believe in the principle of working as a team to maximize the outcomes for our patients. If a urology group is treating somebody with CRPC [castration-resistant prostate cancer], at some given time, that patient may require chemotherapy. And that partnership with a medical oncologist will be key.

So regardless of how you treat the patient or who treats the patient, I think the importance, even in the setting of metastatic castration-resistant prostate cancer, is that you do want to have your patients exposed to all the life-prolonging treatments that we have. There are many changes in the field. We talk about genomics right now, and not only just counseling you for your family history and so forth. For instance, in this case, the patient had a history of colorectal cancer. So the question is, is there potentially a genomic change in your tumor that we can tap for therapeutic purposes? There’s a lot of movement with DNA-repair deficiency in men with prostate cancer. There are new immuno-oncology agents approved for patients with prostate cancer who happen to have microsatellite unstable tumors.

So I think the field is changing drastically. Perhaps the biggest change, in my mind, is for patients who have low-volume metastatic disease. The movement of many of these oral agents is getting pushed all the way to the radiation setting with primary radiation and with salvage radiation therapy. We are obviously pioneers in neoadjuvant concepts, where we actually put patients on oral therapy prior to surgery or even do surgery for high-risk patients and try to minimize their risk of recurrence by adding these novel oral therapies.

Transcript edited for clarity.

Case: Met HSPCa Progressing to mCRPC

June 2016

H&P

• A 64-year old gentleman referred to a medical oncologist with lower back pain
• Initial work-up included:
  • PSA of 79.5 ng/ml
  • WBS showing 3 bone metastasis — 1 Right pelvic area and 2 in lumbar spine
  • CT Chest/Abdomen and Pelvis showed no pelvic lymph nodes and no evidence of visceral disease
  • TRUS/Bx revealed adenocarcinoma of the prostate gland with a Gleason score of 9 [5+4]
• PMH: HTN, Hyperlipidemia - both controlled on oral medications and a family history of colon cancer
• His KPS is 90% and the remaining of his blood work is unremarkable

Pt was started on ADT with LHRH agonist-based therapy and abiraterone + prednisone. He also was placed on monthly zoledronic acid.

• During therapy minimal AEs that included G1 fatigue, hot flashes and muscle aches
• Nadir PSA at 6 months was 0.9 ng/mL

August 2017

• Despite a Testosterone level < 50 ng/dL, patients PSA began to rise
  • PSA August 1.56 ng/mL
  • PSA November 4.4 ng/mL
  • Patient remain completely asymptomatic

February 2018

• Patient is complaining of new back pain (L spine radiating to right hip area) for which he takes over the counter NSAIDs
• PSA now is 6.5ng/mL
• Repeat WBS and CT C/A/P demonstrated 2 new lesions in L spine. No epidural disease or fractures and no evidence of visceral disease.
• Patient is diagnosed as minimally symptomatic Metastatic castration-resistant and abiraterone + prednisone was discontinued.
• Radium 223 therapy was initiated — 6 cycles were completed with improvement of bone pain and minimal AEs that included G1 fatigue and G1 anemia.
  • PSA during therapy ranged from 6.5 to 8.9ng/mL

September 2018

• Patient now is experiencing anorexia, fatigue and progressive abdominal pain
• WBS showed stable disease however CT C/A/P now showed progressive liver metastases
• PSA is now 10.7 ng/ml
• Hemoglobin is 10 g/dL, ANC is 3900 and Platelets are 331,000
• Normal Liver function tests (ALT/AST, Alk Phos, TBili) and LDH of 565

Patients is started on Docetaxel-based chemotherapy (75mg/m2 on 21-day cycles)

Patient completes 6 cycles of therapy with expected AEs including G1 fatigue, G1 alopecia and G1 peripheral neuropathy. His scans at the completion of chemotherapy showed SD with tumor burden reduction in liver lesions and SD in bones. His Hemoglobin level at the completion of chemotherapy is 12.1 g/dL and his ANC and platelets are also within normal limits.