Question
A routine test revealed a prostate-specific antigen (PSA) of 11.5 in a 56-year-old man. Two weeks later, his PSA was 12.1, with a free PSA of 0.4. Ultrasound showed a prostate volume of 29 cm, with a 2-cm "sonic shadow" attached to the capsule. On biopsy, the tumor was diagnosed as an adenocarcinoma, stage T3A, with a Gleason score of 2+3. CT of the pelvis and abdomen were negative, as was a chest x-ray and bone scan. The patient underwent a radical prostatectomy, during which the tumor was measured as 1.5 cm, mostly in the right lobe and partly in the left lobe. The capsule was infiltrated but not penetrated. Spermatic cord and regional lymph nodes were clear. Six months later, his PSA was 1.59. At this point, would you recommend "watch and wait" with rectal ultrasounds every 3 months? Radiotherapy with or without hormonal therapy?
Response
from Zvi Symon, MD, 04/23/2002
This scenario is a classic case of biochemical failure after radical prostatectomy. The pathology following surgery is consistent with a T2BN0 tumor, Gleason score 2+3; clinical staging for metastatic disease was negative. The fact that the capsule was infiltrated but not penetrated may suggest that 1 or more of the inked surgical margins were positive with likely presence of residual disease. Ultimately, the crux of the issue is to determine whether the biochemical failure represents local recurrent/persistent disease or metastatic disease.
A recent study from the Mayo Clinic showed that of the 31% of men who had biochemical failure after radical prostatectomy, PSA doubling time was identified as the most important prognosticator of local and systemic progression. A PSA doubling time of less than 6 months was predictive of systemic progression in 48%, compared with local recurrence in 18% (P < .001).[1]
If the PSA had dropped to zero after radical prostatectomy, a validated PSA of 1.59 6 months later represents a rapid doubling time and suggests both a higher risk of systemic disease, which can be detected via a bone scan and/or an indium-111 capromab pendetide scan, as well as a lower incidence of local recurrence, which can be diagnosed by fiberoptic cystoscopy with visualization and biopsies of the anastomosis/prostatic bed. However, in this case, the low Gleason score, the absence of lymph node and seminal vesicle involvement, and the possible positive margins are more suggestive of residual local disease (with a PSA that did not drop to zero after surgery). Therefore, radiation therapy would be the treatment of choice, even in the absence of biopsy-proven local recurrence.[2,3]
The efficacy of radiotherapy in controlling local recurrence is approximately 40% to 50%. Researchers at Memorial Sloan Kettering Cancer Center[4] have identified 4 risk factors for failure of salvage radiotherapy: (1) pre-treatment PSA > 0.6 ng/mL; (2) margin status; (3) Gleason score > 7; and (4) seminal vessel invasion. Patients with 0, 1, and 2 risk factors had 4-year actuarial PSA relapse-free survival of 94%, 73%, and 22%, respectively. Thus, in this instance, salvage conformal radiotherapy is the preferred treatment option and is associated with a 22% to 73% chance of long-term PSA failure-free survival.[5]
Whether adjuvant hormonal treatment in addition to radiation is useful in this setting is currently under investigation in the Radiation Therapy Oncology Group (RTOG) 9601 trial, which is testing the role of prostatic fossa radiation with or without bicalutamide. Indeed, this patient would likely be a good candidate for participation in this trial.
Patients with low-risk features and slow PSA doubling times are good candidates for expectant management, and treatment may be deferred for years until symptoms develop. Patients with probable metastatic disease would be candidates for immediate vs delayed androgen ablation, which is currently under investigation in the European Organization for Research and Treatment of Cancer (EORTC) 30943 trial.
References
- Roberts SG, Blute ML, Bergstralh EJ, Slezak JM, Zincke H. PSA doubling time as a predictor of clinical progression after biochemical failure following radical prostatectomy for prostate cancer. Mayo Clin Proc. 2001;76:571-572.
- Forman JD, Sharma MC, Lee DJ, et al. definitive radiotherapy following prostatectomy. Results and complications. Int J Radiat Oncol Biol Phys. 1986;12:185-189.
- Koppie TM, Grossfeld GD, Nudell DM, Weinberg VK, Carroll PR. Is anastomotic biopsy necessary before radiotherapy after radical prostatectomy? J Urol. 2001;166:111-115.
- Katz MS, Zelefsky MJ, Venkatraman ES, et al. Risk stratification predicts biochemical outcome after salvage post-prostatectomy three-dimensional conformal radiation therapy. Int J Radiat Oncol Biol Phys. 2001;51(suppl 1):170. Abstract 305.
- Leventis AK, Shariat SF, Kattan MW, Butler EB, Wheeler TM, Slawin KM. Prediction of response to salvage radiation therapy in patients with prostate cancer recurrence after radical prostatectomy. J Clin Oncol. 2001;19:1030-1039.
About the Panel Members
Senior Lecturer, Department of Radiation Oncology, Sackler School of Medicine-Chaim Sheba Medical Center, Tel Aviv, Israel, and Attending physician, Department of Radiation Oncology, Institute of Oncology, Tel Aviv, Israel.
(This is not medical advice but presented solely to allow you to more easily discuss this with your physician who is the only one who can make a diagnosis. - Phoenix5)
