A 65-year-old man was diagnosed with localized prostate cancer
Biopsy revealed adenocarcinoma of the prostate gland, Gleason score 7 [4+3]
PSA 15.7 ng/mL
Baseline staging: T3bN1M0 with right seminal vesicle and pelvic lymph node involvement

Initial Treatment

He undergoes radical prostatectomy with PLND
- PSA nadir of 0.4 ng/mL post-surgery
- Gleason 7 (4 + 3) confirmed
- Positive surgical margins
- Baseline staging confirmed – AJCC Stage IVA

February 2019

Follow-Up Notes

Serum PSA, 38 ng/mL; ALP, 289 IU/L
PSMA PET CT:
- Metastatic retroperitoneal LNs outside resection field
- Abdominal nodes
- Bone mets in ribs and thoracic spine
Genetic testing: BRCA2 mutation-positive

Additional Treatment

Abiraterone + prednisone initiated
Improved pain, PSA, and ALP

October 2019

Follow-Up Notes

Patient reported bone pain
Laboratory testing revealed rising PSA and ALP (serum PSA, 350 ng/mL; ALP, 2500 IU/L)
Imaging showed radiologic progression
ECOG PS 1
PSMA PET CT: increased uptake in retroperitoneal and abdominal LNs

mCRPC Treatment

Treated with docetaxel x4 cycles and denosumab
- Serum PSA, 38 ng/mL; ALP, 289 IU/L
- Reporting bone pain increased in back, now reporting pain in hip area
Bone scan and CT scan:
- Enlargement of retroperitoneal and abdominal LNs
- Additional bone mets noted in pelvic region

Transcript:

Daniel J. George, MD: Hi, I’m Dr Dan George, professor of medicine and surgery in the divisions of medical oncology and urology, and director of GU [genitourinary] oncology at the Duke Cancer Institute, in North Carolina. Today, I’ll be presenting a case of a 65-year-old man with prostate cancer. Our case starts in January 2018 when he was diagnosed initially with localized prostate cancer. A prostate biopsy revealed adenocarcinoma of the gland with a Gleason score of 7; it was 4 plus 3. His pre-biopsy PSA [prostate-specific antigen] was 15.7, and his baseline staging revealed a T3b N1M0 disease with seminal vesicle and pelvic lymph node involvement. He was initially treated with a radical prostatectomy and pelvic lymph node dissection, and his PSA post-surgery nadired at 0.4 nanograms per milliliter. His pathology confirmed a Gleason score of 4 plus 3 cancer, his surgical margins were positive, and by AJCC [American Joint Committee on Cancer] stage he was a stage IVa disease.

The patient’s case goes on to progress, unfortunately, with PSA rising to 38 nanograms per milliliter over the course of about a year. At that point, his alk phos [alkaline phosphatase] is 89, and a PSMA PET [prostate-specific membrane antigen positron emission tomography]-CT reveals metastatic retroperitoneal lymphadenopathy outside of the resection field, now into the retroperitoneum. He has abdominal nodes, evidence of bone metastases with rib and thoracic spine involvement, and he undergoes genetic testing on his tissue and is found to have BRCA2-mutant positive disease. He started on treatment with abiraterone [Zytiga] and prednisone, and he notices an immediate decline in PSA, a slightly delayed decline in alk phos, and improvement in his pain associated with his rib and spine lesions.

Over the course of the next 6 or 8 months, the patient slowly starts to develop recurrent bone pain, and he’s noted to have a rising PSA and alkaline phosphatase. His PSA nadired quickly but then began rising. And by October of 2019, roughly 7 months from his initiation of abiraterone and ADT [androgen deprivation therapy], his PSA is up to 350 nanograms per milliliter, his alk phos is up to 2500, imaging shows clear radiographic progression in his bones, he now has a decreased performance status to 1, and his PSMA PET scan shows further increased uptake of PSMA in his retroperitoneal and abdominal lymph nodes. At this point, the patient is diagnosed with metastatic castrate-resistant prostate cancer, and he’s treated with docetaxel and receives 4 cycles. He’s also started on denosumab for prevention of skeletal events. His PSA declines on the docetaxel down to 38. His alk phos declines as well, from 2500 down to 289. His pain initially responds, but by the fourth cycle, he’s noting recurrence of back pain and pain in his hip area. Repeat staging with a bone scan and CT scan reveal further enlargement of his retroperitoneal and abdominal lymph nodes, and new bone metastases in his pelvic region. Currently, the patient has docetaxel-refractory metastatic castrate-resistant prostate cancer.

This case reflects to me a much more accelerated natural history for prostate cancer than what we typically see. Although the patient presented with what appeared to be an intermediate risk of prostate cancer that was locally advanced at presentation, his disease progression happened rapidly. His PSA nadired at 0.4 and rapidly increased over the course of a year to 38. That’s a very rapid PSA doubling time, in just a matter of weeks.

He subsequently responded to hormonal therapy, and was found to have metastatic disease within a year of that timeframe. Then he responded to hormonal therapy briefly, even with the addition of abiraterone to ADT. His response was a matter of months before, again, he was progressing, and the progression was rapid. It was associated with a very high increase in alk phos, as well as a rapid PSA progression. It suggests that there was inherent resistance present in his disease. It’s not surprising that this patient was a BRCA2-mutated tumor, as these tumors tend to be associated with a much more aggressive course and with other genetic alteration that can drive disease resistance to androgen deprivation therapies. Subsequently, the patient’s treated with docetaxel, and again shows an initial response, but quickly, within a matter of 4 cycles, is having both clinical radiographic evidence of disease progression. It’s this kind of pattern of a brief response and then rapid progression that we see in many of our patients who have BRCA-mutated prostate cancer that typifies this aggressive, accelerated course of disease.

Transcript edited for clarity.