The patient, L.E., is a 72-year-old white male who has been under our care for 10 years. He initially presented to our clinic in 1992, with a diagnosis of localized prostate cancer.
In 1990, the patient had requested that his health-care provider screen him for prostate cancer. Citing the lack of data to support the value of early detection in prostate cancer, that physician had discouraged him from being screened. In 1991, he participated in a local health fair, where he had his prostate-specific antigen (PSA) level tested. Several weeks later, he learned that his PSA level was elevated at 13 ng/mL. His digital rectal exam was normal. Sextant biopsies were performed, revealing a Gleason 4+3, sum 7 in two of six biopsies.
The Gleason sum is an important pathologic scoring system. The most prevalent grade and second most prevalent grade of tumor on the needle biopsy are added together to achieve a Gleason sum. The lowest sum is 2 and the highest is 10. Sums 2-6 are considered low grade; 7 is intermediate; and 8-10 are high-grade cancers.
The patient was in good health and oversaw the activities on a ranch in southern Colorado. He related a past smoking history and moderate alcohol intake. He had no history of any cardiac or pulmonary disease. His father died of prostate cancer at age 93. Bone scans and pelvic computed tomography scans were normal at that time.
He was counseled as to treatment options, and it was recommended that he undergo either a radical prostatectomy or external-beam radiation. During the early 1990s, cryotherapy for prostate cancer was very popular. One patient advocate group strongly recommended this treatment option. There were claims of superior response and less morbidity then either of the two recommendations made to the patient. Despite the fact that this treatment was not covered by his health-care insurance, the patient chose cryotherapy.
In June 1992, the patient underwent cryotherapy for his prostate cancer. His postoperative course was complicated in that he was urinating flecks of tissue and had two episodes of urinary retention, necessitating placement of a Foley catheter. He maintained his potency for 3 months and then experienced the gradual onset of erectile dysfunction. At 18 months posttherapy, his PSA was
In 1995, he was diagnosed with colon cancer and treated with a partial colectomy. Pathology revealed a Duke’s class C carcinoma of the colon. He was treated with adjuvant chemotherapy consisting of fluorouracil (5-FU) plus levamisole (Ergamisol). At the present time, he is considered to be disease-free.
Because of persistent erectile dysfunction and lack of response to sildenafil (Viagra) and alprostadil injections, a penile prosthesis was inserted. Both he and his partner were very satisfied with the results.
Over the past 3 years, his PSA has begun to rise. In April 2000, when his PSA level reached 3.1 ng/mL, prostate biopsies were obtained in an attempt to document a local recurrence (Figure 1). No evidence of malignancy was found. The patient did not have a follow-up until October 2001, when his PSA level was 5.4 ng/mL. He had no new complaints, but was concerned about the implications of the rising PSA. He stated that he wanted us to keep him alive for at least another 10 years.
The physical examination revealed a healthy 72-year-old male. A penile prosthesis was in place, and the digital rectal exam showed a 25-g small fibrotic prostate with no nodularity. For this conference, a bone scan and ProstaScint scan were obtained.
In summary, we have a healthy 72-year-old male diagnosed with prostate cancer in 1991. He was treated with a nontraditional therapy—cryotherapy—and has done reasonably well, with the exception of biochemical failure. The patient is quite concerned about the implications of the rising PSA blood test.
Dr. Michael Glode: Dr. Lucia, what is your feeling about the difference, if any, between Gleason patterns 4+3 vs 3+4?
Dr. Scott Lucia: Data from the Stanford and Wayne State groups show that the greater the volume of a high-grade component (Gleason grade 4 or 5), the worse the prognosis. Thus, disease-free survival following prostatectomy is lower for 4+3 tumors compared to 3+4 tumors at 5 years. These data are for prostatectomy specimens; it is not clear that this holds for biopsies. D’Amico in 1999 reported that 5-year PSA failure-free survival was significantly lower in patients whose biopsy scores were 4+3 vs 3+4. However, sampling is a major problem with needle biopsies. Therefore, the difference between a 3+4 and 4+3 biopsy may be more of a sampling issue than a truly prognostic one.
Dr. Andrew Kraft: How accurate are biopsies in determining the presence of prostate cancer in a gland following radiation therapy, or in this case, cryotherapy?
Dr. Lucia: Certainly if tumor is present we can diagnose it on biopsy. However, although I still grade tumors following radiation therapy, some feel that Gleason grading can be inaccurate following therapy. There can be sampling errors by which persistent cancer is missed.
Local vs Distant Recurrence
Dr. Marcus Chen: The patient’s bone scan has a small linear focus of increased activity involving the left anterior pubic ramus, which is not suspicious for metastases (Figure 2). There are no other areas of focal increased uptake. The ProstaScint scan demonstrates activity in the region of the prostatic bed, suspicious for prostate cancer recurrence (Figure 3). There is no focal increased activity in the pelvic lymph nodes.
Dr. E. David Crawford: Biochemical failure is the most common presentation for advanced prostate cancer. To me, and I believe to patients, advanced is synonymous with incurable. In many patients with biochemical failure there is a risk of dying "of" rather than "with" prostate cancer. In a manuscript published 3 years ago, we labeled this stage D1.5. (This refers to a rising PSA after failed local therapy.) Less than a decade ago, most patients with advanced prostate cancer presented with bone metastasis stage D2 (Tx, Nx, M+). Early-detection efforts have changed this pattern. A great deal of controversy exists regarding treatment for stage D1.5. Unfortunately, we don’t have any randomized clinical trials to address this issue.
In evaluating these patients, I ask two important questions: First, was this patient curable when initially diagnosed? And second, does this represent a local recurrence, a distant recurrence, or a combination of both?
A patient with an initial Gleason sum of 5, a PSA of 6 ng/mL, and a normal rectal exam (T1C) should be curable with local modalities. A patient with an initial Gleason sum of 8, PSA of 32 ng/mL, and a rock hard prostate is not going to be cured with local therapies such as radical prostatectomy or radiation therapy alone. This patient is in a gray zone. If we look up his chance of failing in well-publicized tables or artificial neural networks, again he is in a gray zone.
Using our artificial neural network programs (http://www.annsincap.org or www.prostatecalculator.org), which provide a method of analyzing multiple variables, he has a 57.3% chance of having extracapsular disease, an 84% 5-year chance of having a now rising PSA (undetectable) and a 76% chance at 10 years, all based on radical prostatectomy figures. Our current radiographic staging would suggest that this is a local rather than a distant recurrence.
Another factor in the patient’s history that favors a local rather than a distant recurrence is the fact that his PSA fell to a low level and gradually rose only in the past couple of years. Men who fail to reduce their PSA to negligible levels or have a rise in the first 18 months of therapy are more likely to have distant disease. A third factor favoring local disease is the slow doubling time of the PSA.
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