Challenging Cases in GU Malignancies: Panel Discussion

This ASTRO panel was moderated by Anthony D’Amico, MD, PhD

The panel discussion was based on the case of a 54-year-old man with no significant past medical history other than hair loss, for which he was receiving treatment with Propecia (finasteride) . His current prostate-specific antigen (PSA) level was 1.5 ng/mL; 1 year ago it had been 0.5 mg/mL. Dr Anthony D’Amico noted that the treatment has the same impact on PSA that it has in the setting of benign prostate hyperplasia: after 6 months, PSA is reduced by approximately half and needs correction. In this case, the corrected PSA would be 3.0 ng/mL. The patient’s testosterone level was 547 ng/dL, which is within normal limits. A digital rectal exam revealed a right nodule at the base, spanning more than half the lobe, which was at clinical stage T2b. The patient underwent a 12-core transrectal ultrasound-guided prostate biopsy with 4 cores taken from the nodule-containing area. The biopsy results revealed Gleason grade of 4+3 (in the right mid and base posteriorly and laterally), indicating unfavorable intermediate-risk prostate cancer.

The discussion started by considering the available choices for imaging. If the patient is interested in pursuing surgical intervention with a radical prostatectomy (RP), multiparametric magnetic resonance imaging (mpMRI) should be considered. In this patient a bone scan is unlikely to be positive. One discussant noted that, in his practice, the mpMRI would have been done prior to the patient undergoing a prostate biopsy.

Dr D’Amico questioned whether a positron emission tomography (PET) scan would have any utility for this patient. A panelist responded that, in the United Kingdom, a PET scan would not be obtained in this case because the patient is not at high risk. She noted that prostate-specific membrane antigen PET (PSMA-PET) imaging currently is not approved in her country, although it is available at certain centers.

Another panelist, who is a medical oncologist, opined that he would fully stage this patient with a bone scan, even though it is likely to be negative. He noted that use of mpMRI would have the added benefit of identifying further tumor burden and could potentially influence treatment choice.

Dr D’Amico continued to explain the case: the patient underwent a bone scan that was negative; mpMRI showed a PIRADS-5 lesion at the right anterior base with possible bladder neck invasion and a 0.9 cm left external iliac lymph node that was equivocal. Dr D’Amico reinforced that it is considered equivocal because it would have to be at least 1.5 cm to be classified as a positive lymph node. The patient subsequently underwent a magnetic resonance– transrectal ultrasound fusion prostate biopsy of the lesion, and the Gleason grade was adjusted to 5+4.

The ensuing conversation focused on appropriate treatment for this patient. The options included: (1) RP and pelvic lymph node dissection, with a possible need for postoperative radiation therapy (RT) and androgen-deprivation therapy (ADT); (2) external beam radiation therapy (EBRT) and prostate salvage radiotherapy + ADT with or without abiraterone for 2 years; or (3) obtaining additional imaging.

One panelist thought that surgical intervention with RP should be encouraged, “not only for the therapeutic aspect but also the added benefit of being able to assess the lymph nodes for a better prognosis.” He believed it is important to preoperatively counsel the patient that there is a possibility of positive margins or more extensive disease, in which case he would likely be a candidate for postoperative radiation. If the patient were to undergo RT, he would be a good candidate for brachytherapy. It was noted that PSMA-PET should be performed prior to RT to assess lymph node status and the possibility of other metastatic lesions.

Dr D’Amico next asked how bladder neck invasion might change the indication for brachytherapy in this patient. The discussion then focused on the benefit of brachytherapy because the optimal dose for primary disease and treatment can extend readily to include the seminal vesicles or a known invasion of the bladder neck.

The forum moved on to debating management of lymph node involvement, and whether there is any benefit to performing surgery for the purpose of lymph node excision. The panelists generally agreed that PSMA-PET would be beneficial before intervention. Because lymph node resection is based on a template, and a 0.9-cm node will look normal intraoperatively, it is unlikely to change the pelvic lymph node dissection significantly. In the bladder neck, surgery could be modified to try to obtain negative margins by taking a wider margin of the bladder neck. This would have minimal impact on the bladder neck because the key to continence recovery is the quality of the apical dissection, which has a more favorable impact than wider bladder neck excision.

Dr D’Amico presented the next part of the case: the patient was given a PSMA-PET scan, and the pelvic lymph nodes were found not to be PET-avid. He then underwent a left-side nerve-sparing RP and pelvic lymph node sampling. Seminal vesicle invasion was found on the right side. Negative results were found in the 14 lymph nodes that were sampled, but there was a positive bladder neck margin. The Gleason grade was determined as 5+4. At 4 weeks postoperatively, the patient’s PSA was undetectable; however, he complained of erectile dysfunction and stress urinary incontinence. A Decipher score was obtained on the pathology from the RP, and the patient was found to be in the intermediate-risk group. Dr D’Amico explained that the Decipher score is a 22-gene genomic classifier that can predict risk of metastasis up to 5 years postoperatively. Summarizing that this was a case of a patient with high-risk features and an intermediate Decipher score, he asked panelists what they would consider to be the next step options included: (1) PSA surveillance until a PSA level of 0.10 ng/mL, followed by pelvic lymph node and prostate bed RT with ADT; (2) adjuvant pelvic lymph node and prostate bed RT with ADT; (3) PSA surveillance until a PSA level of 0.10 ng/mL, followed by prostate bed RT with ADT; or (4) adjuvant RT to the prostate bed with ADT.

A panelist from the UK pointed out that her country currently does not use the Decipher score. Because the PSA is undetectable, the first inclination would be to wait and not rush to treatment. There was significant agreement among the panelists regarding this approach. Most thought a PSA should be obtained every 6 to 8 weeks. Although there is a good chance that the patient might need additional therapy, given his Gleason grade and pathology, they recommended trying to have him achieve continence before pursuing additional therapies. There is no evidence that earlier treatment is better in the setting of an undetectable PSA. They also thought the appropriate time to weigh the benefit of adjuvant versus early salvage treatment would be after continence was recovered, if the patient was feeling better, and PSA assessment could be moved to every 6 to 12 months.

Dr D’Amico presented the audience with another challenge: If this patient returns in 6 months, with a PSA level of 0.05 ng/mL, and he still has mild ED but is continent, what should be done?

One panelist shared a study showing that, in a patient with a PSA <0.02 ng/mL, there can be a benefit from treatment. The panelist suggested advising the patient that he has concerning risk factors, and that while the first step was close observation, it might be time to consider treatment. The patient should be made to understand that although there might not be an imperative to begin treatment immediately, he will likely need it in the near future.

Dr D’Amico mentioned that there are randomized trials—the most famous of which is the RADICALS trial— comparing adjuvant with early salvage therapy, but none has shown a statistically significant difference between the treatments. He noted, however, that the trials did not contain many patients in their populations who were similar to the one in the current case; the patients in those trials did not have multiple high-risk factors. He indicated that there is some level 2 evidence suggesting that such patients may benefit from earlier rather than later treatment. He opined that at his institution they would discuss treatment options, including radiation to the nodes, prophylactically to the bed, plus 6 months of ADT. However, he underlined that this approach is not based on level 1 evidence.

One panelist disputed this approach, noting that many experts would not go on to administer radiation to the nodes, given that, on resection, the nodes were negative. Dr D’Amico responded that there is a trial in which PSMA-PET showed that 80% of patients had node-negative disease yet received benefit from pelvic- node treatment, although they did not receive surgical resection. He gave the rationale that, because PSMA-PET cannot see microscopic disease in the pelvic lymph nodes, patients may benefit from a prophylactic radiation dose to the lymph nodes even in the setting of a negative PSMA- PET result.

David Ambinder, MD is a urology resident at New York Medical College/Westchester Medical Center. His interests include surgical education, GU oncology and advancements in technology in urology. A significant portion of his research has been focused on litigation in urology.