Case 21-2004 — A 63-Year-Old Man with Metastatic Prostate Carcinoma Refractory to Hormone Therapy
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《新英格兰医药杂志》
Presentation of Case
A 63-year-old man was evaluated in the clinic because of metastatic prostate cancer that was no longer responding to hormone therapy.
The patient had been well until eight years before he came to the clinic, when he had noticed a decreased urinary stream and urinary hesitancy. A test for prostate-specific antigen (PSA) six months later showed a level of 2.7 ng per milliliter; six months after that, the PSA level was 7.7 ng per milliliter. A transrectal needle biopsy of the prostate showed adenocarcinoma, Gleason grade 3 to 4 (on a scale of 1 to 5, with 1 indicating low-grade carcinoma, and 5 high-grade carcinoma), involving all the biopsy cores (Figure 1A and Figure 1B). Computed tomographic (CT) scans of the abdomen and pelvis and a bone scan showed no abnormalities. The general physical examination also showed no abnormalities. Rectal examination revealed a firm, nodular area, 2 to 3 cm in diameter, that involved the left lobe of the prostate and that appeared to go to the edge of the gland. The right lobe was diffusely firm. Laboratory studies and chest radiographic studies showed no abnormalities.
Figure 1. Biopsy Specimens of the Prostate and a Paraaortic Lymph Node (Hematoxylin and Eosin Stains).
The initial, diagnostic biopsy specimen obtained contains extensive adenocarcinoma with several patterns (Panel A, x31). A large glandular pattern and a focal cribriform pattern, graded as Gleason 3C/5 was prominent, but there were also small fused glands (Gleason grade 4/5) (Panel B, x250), for a Gleason score of 7/10. The lymph-node biopsy specimen obtained at laparotomy (Panel C, x31) contains a large nodule (Gleason grade 4/5 adenocarcinoma) with a fused glandular pattern, similar to that seen in some areas of the prostate.
Two months later, the patient was taken to the operating room for a radical prostatectomy. On intraoperative examination of specimens obtained by bilateral pelvic lymph-node biopsy, involvement by metastatic prostate cancer was grossly evident (Figure 1C). The procedure was terminated, and the prostatectomy was not performed. After the operation, the patient's disease was staged as T2N2M0 (a tumor that is palpable or visible on ultrasound, involves both lobes, is associated with more than one positive regional lymph node, and is not accompanied by distant metastases). He was discharged, and treatment with flutamide at a dose of 250 mg three times daily was prescribed. Two months later, the patient's PSA level was 1.1 ng per milliliter. External-beam radiation treatments were administered, with a total dose of 69.4 Gy, and were completed six months after the initial diagnosis.
At that time, the patient's PSA level was 0.5 ng per milliliter, and it remained at or below that level for the next six years while he continued taking flutamide. Magnetic resonance imaging (MRI) of the lumbar spine that was performed four years after the diagnosis showed no abnormalities, and the results of all liver-function tests were normal. Five and a half years after the diagnosis, a bone scan showed no abnormalities. Six years after the diagnosis, the patient's PSA level was 0.2 ng per milliliter.
Eleven months later, the PSA level was 0.9 ng per milliliter; one month after that (seven years after the initial diagnosis), it was 1.4 ng per milliliter. The daily flutamide treatment was discontinued. One month later, a bone scan showed increased uptake at the T11 vertebra, which was suggestive of metastatic disease, but an MRI scan showed no abnormalities. Over the next five months, the patient's PSA level rose to 4.0 and then to 6.6 ng per milliliter. An abdominopelvic CT scan showed newly enlarged retroperitoneal lymph nodes, which were thought to represent metastatic disease. A bone scan showed no metastatic disease.
One month later, leuprolide by intramuscular injection was begun at an initial dose of 7.5 mg, followed one month later by 22.5 mg, which was then given every three months. Four months later, the PSA level was 6.4 ng per milliliter. A bone scan obtained one month later showed metastatic disease at T10, L5, the right humerus, and the ribs bilaterally (Figure 2A). An abdominopelvic CT scan obtained the same day showed progression of the retroperitoneal lymphadenopathy and a newly enlarged lymph node in the right retrocrural area (Figure 3A). A CT scan of the chest showed multiple pulmonary nodules and mediastinal and left hilar lymphadenopathy, which were thought to represent metastatic disease (Figure 4A).
Figure 2. Bone Scans Obtained before and after Chemotherapy.
A scan obtained 7 years and 10 months after the diagnosis (Panel A) reveals metastatic lesions (arrows) in the lower thoracic and lumbar spine. Seven weeks after the initiation of chemotherapy (Panel B), the lesions show increased activity (arrows). This "flare" phenomenon results from an increase in osteoblastic activity in healing bone lesions.
Figure 3. Axial CT Images of the Abdomen Obtained after the Intravenous Administration of Contrast Material.
A CT image obtained 7 years and 10 months after the diagnosis reveals an enlarged lymph node close to the aortic bifurcation (Panel A, arrow). An image from a repeated CT scan obtained at the same level seven weeks after the initiation of chemotherapy shows diminution in the size of the pelvic lymph node (Panel B, arrow).
Figure 4. Axial CT Images of the Chest Obtained after the Intravenous Administration of Contrast Material.
An image obtained seven years and eight months after the diagnosis shows multiple nodules in both lungs (Panel A, arrows). An image obtained seven weeks after the initiation of chemotherapy shows a decrease in size and cavitation of some of the nodules (Panel B, arrows).
Discussion of Management
Dr. Donald S. Kaufman: Over a span of eight years, this man has been cared for by urologists, radiation oncologists, and medical oncologists, and his care has included prostate biopsies, an exploratory laparotomy, radiation treatment, and hormone therapy. Each of these treatment decisions required a risk–benefit analysis, from his initial presentation with an elevated PSA level, when the primary treatments considered included radical prostatectomy and intensive radiation treatment, to his current evaluation, when a decision about the use of chemotherapy had to be made in the context of widespread disease.
Dr. Young, would you show us the slides of the specimens from the initial prostate biopsy?
Dr. Robert H. Young: Most of the cores were extensively involved by adenocarcinoma, even more extensively on the left side than on the right side. The pattern was not that of the usual small acinar adenocarcinoma that is seen in 80 to 90 percent of prostate cancers, but rather a pattern of larger glands. Some areas were well differentiated and were classified as Gleason grade 2, and some were Gleason grade 3C, with a cribriform pattern (Figure 1A). Some clinicians believe that Gleason grade 3 carcinomas with a cribriform pattern have a somewhat worse prognosis than Gleason grade 3 adenocarcinomas without a cribriform pattern. In other areas, there were fused small glands in a packed, microacinar pattern typical of a Gleason grade 4 adenocarcinoma (Figure 1B). The Gleason score, as opposed to grade, was 7 (the sum of the two highest grades, in this case 3 and 4).
Management of Localized Prostate Cancer
Dr. Kaufman: At the time of his initial presentation, the patient appeared to have cancer localized to the prostate. The treatment options included radical prostatectomy and radiation therapy. I would like to ask Drs. McDougal and Shipley to discuss the roles of radical prostatectomy and radiation therapy in the curative treatment of this patient.
Radical Prostatectomy
Dr. W. Scott McDougal: Radical prostatectomy has several advantages: examination of the specimen offers definitive knowledge of the pathological stage and grade of the disease, and the patient benefits from what I consider the most durable method of disease eradication over the long term. Patients may be stratified according to the pathological stage of their disease. If the Gleason score is 2 to 4 and the clinical stage is T1c (i.e., the patient has an elevated PSA level without a palpable mass), the progression-free survival rate after a radical prostatectomy is approximately 90 percent; if the Gleason score is 5 to 6, the rate is about 80 percent; if the score is 7, the rate is about 55 percent; and if the score is 8 to 10, the rate is less than 20 percent.1 For patients who have T2 disease, such as the patient under discussion, the probability of 15 years of progression-free survival is approximately 69 percent. The higher the Gleason score, and the more extensive the disease, the greater the likelihood of intraoperative and postoperative complications. Intraoperative complications include bleeding and injury to the obturator nerve, the urethra, the rectum, or a major pelvic artery or vein. Postoperative complications may substantially alter the patient's quality of life; they fall into three categories: incontinence, impotence, and urethrovesical stricture.
The incidence of complications reported by primary caregivers in single-institution studies tends to reflect better results than the incidence reported by investigators who are not the primary caregivers in large, multi-institution studies. The incidence of urethrovesical stricture, for example, varies from less than 1 percent to 9 percent. The incidence of incontinence in single-institution studies is about 8 percent, with 6 percent of the patients having stress incontinence and 2 percent wearing more than one pad a day. In assessments of incontinence in multi-institutional studies one year after the surgery, about one third of the patients are reported to wear a pad.2 Potency rates also vary, depending on who asks the question of the patient, the age of the patient, and the patient's erectile status before the operation. In studies in which the patient's own assessment is used, potency rates vary from 90 percent in patients less than 50 years of age to 25 percent in those greater than 70 years of age.3 However, when patients are assessed with the use of appropriate outcome measures by a disinterested third party in multi-institutional studies, only 31 percent of patients report that they have an erection and only 9 percent report successful intercourse.2 In a population-based study of 1291 men who were evaluated 18 or more months after radical prostatectomy, 8 percent were incontinent and 60 percent were impotent.4
This patient was thus a good candidate for radical prostatectomy, and at the age of 55 years, he had a low risk of side effects.
Radiation Therapy
Dr. William U. Shipley (Radiation Oncology): The advantages of external-beam radiation therapy as the primary treatment for this patient with localized prostate cancer are that it poses a very low risk of urinary incontinence and stricture; it may eradicate extensions of the tumor beyond the capsule of the prostate; and when it is combined with hormonal therapy, it may offer a chance of cure for some patients, such as this one, with intermediate-risk tumors. The disadvantages of radiation therapy are that the treatment is long, eight to nine weeks; a three-dimensional, conformal technique that allows the delivery of doses of at least 72 Gy may be required; and the treatment adds a low risk of subsequent rectal symptoms. In addition, this therapeutic method does not inform the clinician about possible metastases to lymph nodes, and the long-term sequelae of ultra–high-dose radiation treatments are not known.
The chance of recurrence-free survival after irradiation, with the use of post-treatment PSA level as the monitoring criterion, can be predicted by the risk group of the patient at presentation. For patients with low-risk tumors (stage T1c, a Gleason score of 6 or less, and a PSA level of 10 ng per milliliter or less), the rate is 70 to 80 percent.5 This patient had an intermediate-risk tumor (stage T2 tumor, Gleason score 7, and an initial PSA level of 10 to 20 ng per milliliter), and his expected chance of survival would range from 50 to 55 percent if he were given conventional external-beam radiation therapy alone.
Over the past decade, the development of three-dimensional conformal therapy, which uses computer software to integrate CT images of the patient's internal anatomy in the treatment position, has allowed the volume of tissue to which a high dose of radiation is delivered to conform more exactly to the shape of the tumor. This advance has reduced the incidence of both early and late toxic effects on normal tissue in patients with prostate cancer and allows higher cumulative doses to be delivered with a reduced risk of late effects.6,7 There is now evidence from both randomized and nonrandomized clinical trials of significant improvement in the rates of recurrence-free survival in patients with intermediate-risk tumors when doses greater than 70 Gy are used.8,9,10 In addition, patients who have intermediate-risk tumors have significantly higher disease-specific survival rates with a short course of neoadjuvant androgen-suppression therapy and radiation treatment than they do with radiation treatment alone.10
Thus, the current recommendation for this patient would be irradiation to a total dose of 75 to 76 Gy by the three-dimensional conformal technique, preceded by a short course of neoadjuvant androgen suppression. In recent reports, the rates of disease progression 6 to 10 years after irradiation are similar to those in reports of series of patients undergoing prostatectomy.8,11
Strict contraindications to external-beam radiation therapy include prior pelvic irradiation, active inflammatory bowel disease, a permanent Foley catheter, and morbid obesity. For this patient, who had none of these problems, radiation therapy is a reasonable alternative to radical prostatectomy.
Dr. Kaufman: Both radical prostatectomy and conformal external-beam radiation treatment can cure localized prostate cancer; cure is more likely for patients with low-risk disease than for patients in the intermediate-risk and high-risk groups. The incidence of serious incontinence after radical prostatectomy is about 5 percent when the procedure is performed by experienced surgeons and virtually nonexistent after radiation treatment; the rate of impotence is about 50 percent after either treatment. Not surprisingly, surgeons prefer prostatectomy and radiation oncologists favor irradiation as the treatment of choice.12 No prospective comparative study of conformal external-beam radiation treatment with higher total doses of radiation and surgery has been reported.
After consultation with his physicians, this patient chose to undergo radical prostatectomy. At laparotomy, enlarged pelvic lymph nodes were seen. Dr. Young, would you describe the specimens for us?
Dr. Young: On intraoperative gross examination, the three right obturator lymph nodes sampled were rubbery in texture and ranged from 0.5 to 2.0 cm in greatest dimension; the single left obturator lymph node was 1.4 cm in its greatest dimension and contained a nodule of firm, tan-to-white tissue, a finding indicating the presence of tumor. On microscopical examination of both frozen and permanent sections (Figure 1C), the tumor had a small, acinar, fused glandular pattern similar to that seen in the prostate biopsy specimen. Two of the three lymph nodes on the right side and the one on the left side contained cancer.
Management of Locally Advanced Prostate Cancer
Dr. Kaufman: Dr. Gomery, you were the surgeon caring for this patient. Please tell us what you did and the reasons for your decisions.
Dr. Pablo Gomery (Urology): Because the biopsy had revealed a rather poorly differentiated prostatic carcinoma and examination of several lymph nodes had shown grossly evident carcinoma, I believed that the likelihood of a cure for this patient by prostatectomy was low and did not justify the potential complications of the operation in a man of his age who was sexually active, so I terminated the procedure without completing the prostatectomy.
Dr. Kaufman: Dr. Zietman, what is the role of radiation treatment in this patient, who had positive nodes and in whom surgery was aborted?
Radiation Therapy
Dr. Anthony L. Zietman: More than 90 percent of patients who have node-positive prostate cancer have occult metastatic disease elsewhere. As a consequence, cure is unlikely with any localized therapy. Many patients, however, have bulky or aggressive disease at the primary site, which may cause local symptoms and may be the first site of tumor progression. Two studies, one from the M.D. Anderson Cancer Center13 and one from this institution,14 found that in patients treated with androgen deprivation alone, the primary site was the most common first site of progression, requiring subsequent local therapy in up to 73 percent of the patients. In contrast, of the patients treated with both androgen deprivation and local therapy (radiation therapy or transurethral prostatectomy), local recurrence of disease requiring therapy developed in 11 percent or less.
Local therapy plus androgen deprivation may therefore be justified to extend the initial disease-free interval and to reduce symptomatic local progression. In this patient, I recommended radiation therapy; this was before the days of three-dimensional conformal treatment, and he received what was then our standard dose — approximately 69 Gy.
Dr. McDougal: The fact that you treated him locally does not necessarily mean that you eradicated the local disease or eliminated the possibility of local progression.
Dr. Zietman: Absolutely not.
Dr. Kaufman: The patient did not experience any local side effects from the radiation therapy, and he stated that his sexual potency was unaffected. He was free of symptoms for seven years after the diagnosis; then, while he was receiving flutamide, the PSA level rose to 0.9 ng per milliliter and then to 1.4 ng per milliliter. The flutamide was discontinued. Intramuscular leuprolide was begun six months later, but the PSA level continued to rise. A bone scan and chest and abdominal CT scans were obtained four months later.
Dr. Mukesh G. Harisinghani: The bone scan at this time (Figure 2A) shows areas of increased uptake in T10, the ribs bilaterally, and the right humerus. Images from a contrast-enhanced CT scan of the abdomen and pelvis (Figure 3A) show newly enlarged retroperitoneal lymph nodes adjacent to the upper and lower abdominal aorta and the bifurcation — a finding that probably represents metastatic disease. The lung windows from the chest CT scan (Figure 4A) show multiple nodules in both lungs, and the mediastinal windows show enlarged precarinal and subcarinal lymph nodes; all of these findings almost certainly represent metastatic disease.
Dr. Kaufman: What are the treatment options at this point? The patient has been receiving leuprolide for four months, with no improvement. Dr. Smith, would you discuss hormone treatment for advanced prostate cancer?
Hormonal Therapy
Dr. Matthew R. Smith (Hematology/Oncology): Androgen-deprivation therapy by either bilateral orchiectomy or administration of a gonadotropin-releasing hormone agonist such as leuprolide is the mainstay of treatment for advanced or metastatic prostate cancer. Androgen-deprivation therapy by either method decreases serum testosterone levels by more than 95 percent and leads to objective responses in the majority of patients. Monotherapy with antiandrogens is an alternative to standard androgen-deprivation therapy. Flutamide is a nonsteroidal antiandrogen that blocks the action of testosterone by binding to the androgen receptor in target tissue. This man's disease responded to flutamide monotherapy for more than six years. About two thirds of men with progressive disease who receive antiandrogen monotherapy will respond to subsequent androgen-deprivation therapy. The long duration of the response to flutamide monotherapy in this case suggests a higher-than-average chance of a response to subsequent medical or surgical castration. In addition, in a few men treated with a gonadotropin-releasing hormone agonist, testosterone levels approaching those achieved by bilateral orchiectomy are not reached. I recommend the measurement of serum-testosterone levels for patients who either do not have a response or who have unexpectedly short responses to a gonadotropin-releasing hormone agonist. Bilateral orchiectomy may prove effective in the men whose testosterone production cannot be adequately suppressed with a gonadotropin-releasing hormone agonist.
Dr. Kaufman: Given the patient's progression of disease while he was receiving hormonal treatment, we considered multiagent chemotherapy. Dr. Michaelson, would you discuss the role of chemotherapy in the treatment of a patient, such as this one, who has advanced, hormone-refractory prostate cancer?
Chemotherapy
Dr. M. Dror Michaelson (Hematology/Oncology): The early experience with cytotoxic chemotherapy in prostate cancer was largely unsuccessful, and until the 1990s, chemotherapy was not considered a standard treatment for this disease. Two randomized, phase 3 studies in the mid-1990s showed a benefit with mitoxantrone and corticosteroids as compared with corticosteroids alone, with improvement in the patients' scores on pain scales and in their overall quality of life.15,16 However, even this combination produced a decrease in the PSA level in only 30 to 35 percent of the patients. The same studies also failed to show a benefit in overall or disease-specific survival among patients treated with mitoxantrone and corticosteroids as compared with those treated with corticosteroids alone.
Taxane-based regimens have now been studied in numerous phase 1 and 2 clinical trials, and they appear to be more promising than previously studied therapies. Paclitaxel and docetaxel alone or in combination with estramustine, with or without carboplatin and etoposide, have been studied in multiple phase 1 and 2 trials. Many of these trials have documented response rates in excess of 50 percent.17,18 In response to these data, an Intergroup phase 3 study comparing docetaxel and estramustine with the current standard therapy, mitoxantrone plus corticosteroids, is under way.
In the past few years, clinical trials have evaluated the usefulness of adding a third agent to the combination of docetaxel and estramustine. These have included biologic agents targeted against growth-factor pathways and traditional cytotoxic chemotherapy drugs. At this hospital, my colleagues and I have conducted a study of a regimen that combines docetaxel, estramustine, and carboplatin in men with hormone-refractory prostate cancer. Accrual to this study has been completed, but the results are not yet available. The patient under discussion was enrolled in this trial.
Dr. Kaufman: Eight years after the initial diagnosis, chemotherapy consisting of docetaxel, estramustine, and carboplatin was initiated, carried out for six cycles, and completed in six months. During the six months of chemotherapy, the patient had virtually no symptoms except for very mild fatigue. He did not miss work and was able to continue his activity of mountain climbing. His PSA level dropped to 0.5 ng per milliliter shortly after the start of chemotherapy, and at the completion of chemotherapy his PSA level was less than 0.2 ng per milliliter.
Dr. Harisinghani, would you show us the images that were obtained after the treatment?
Dr. Harisinghani: On the bone scan obtained seven weeks after the start of chemotherapy (Figure 2B), the preexisting lesions all showed increased activity. This phenomenon, which has been called a flare, represents increased osteoblastic activity within the metastases, which is a sign of improvement after treatment. No new lesions were identified. The paraaortic lymphadenopathy has regressed in size as compared with that seen on the previous abdominal CT scan (Figure 3B). A chest CT scan obtained at the same time reveals that the pulmonary nodules have regressed in size (Figure 4B) and show some cavitation, indicating a response to therapy. The mediastinal nodes have all decreased in size.
Dr. Kaufman: These images illustrate an important point. When the patient's chest and abdominal CT scans showed that there had been dramatic improvement, the bone scan was initially read as revealing an increase in metastatic disease. On review, however, it became clear that this finding was a flare reaction — all of the increased uptake was in areas that had previously been involved by tumor. This is a rare phenomenon that occurs as a result of treatment, and it is important to recognize.
Unfortunately, four months after the completion of chemotherapy, the patient's PSA level began to rise, and three months later — nine years after the initial diagnosis and one year after the initiation of chemotherapy — it was 6.3 ng per milliliter. Repeated CT scans revealed stable lung nodules. An abdominopelvic CT scan showed an increase in the size of the left paraaortic lymph nodes. A bone scan showed a new lesion in the T9 vertebral body and a lesion in T10 that had increased in size.
Because of his good response and because he did not have a toxic reaction to the chemotherapy regimen, we decided to treat him again, using the same agents. At the time of the first chemotherapy visit, he reported smoky vision in his left eye, with no gait disturbance or headaches. He was evaluated by a vitreoretinal specialist, who conducted fluorescein testing, indocyanine green angiography, and optical coherence tomography; a 1-mm area of thickening was observed, a finding consistent with a single choroidal metastatic lesion on the left retina. After one cycle of chemotherapy, the patient noted an improvement in visual clarity. His PSA level decreased from 6.0 to 3.0 ng per milliliter after the first cycle of chemotherapy; after seven cycles, his PSA level was less than 0.2 ng per milliliter.
Dr. Alex F. Althausen (Urology): What is the average duration of tumor-free survival for a patient who presents with known nodal disease and is given all these therapies? Is this patient's course unusual in being protracted over nine years? Or, can we tell patients that even if the results of an MRI or CT scan are positive for cancer, with appropriate chemotherapy they can expect nine or more years of a reasonable quality of life?
Dr. James Talcott (Medical Oncology): This patient's long survival is unusual, but the course of prostate cancer is highly variable, even after adjustments for tumor stage, Gleason score, and PSA level. Earlier diagnosis as a result of PSA screening has led to a longer survival for all patients, through "stage migration."19 In a small, randomized trial of immediate hormone treatment as compared with treatment at the time of clinical relapse in patients, such as this man, with positive nodes, survival was improved in the immediate-treatment group,20 but growing evidence of toxicity from long-term androgen-deprivation therapy suggests that discussion should precede chemical castration of asymptomatic men without metastases.21
Dr. Kaufman: At the most recent follow-up, the patient's PSA level was 0.2 ng per milliliter. A bone scan and abdominal, pelvic, and chest CT scans all showed stable disease. Unfortunately, his eye lesion recently recurred, and he is now receiving proton-beam therapy to the eye. In the care of this patient over what is now a 10-year span, we have used almost every known treatment for prostate cancer. Remarkably, the patient has felt well throughout the entire course of his illness, carrying on with his normal occupation and activities.
Anatomical Diagnosis
Adenocarcinoma of the prostate with metastases.
Source Information
From the Division of Medical Oncology, Department of Medicine (D.S.K.), and the Departments of Urology (W.S.M.), Radiation Oncology (A.L.Z.), Radiology (M.G.H.), and Pathology (R.H.Y.), Massachusetts General Hospital; and the Departments of Medicine (D.S.K.), Urology (W.S.M.), Radiation Oncology (A.L.Z.), Radiology (M.G.H.), and Pathology (R.H.Y.), Harvard Medical School.
References
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Talcott JA, Rieker P, Clark JA, et al. Patient-reported symptoms after primary therapy for early prostate cancer: results of a prospective cohort study. J Clin Oncol 1998;16:275-283.
Quinlan DM, Epstein JI, Carter BS, Walsh PC. Sexual function following radical prostatectomy: influence of preservation of neurovascular bundles. J Urol 1991;145:998-1002.
Stanford JL, Feng Z, Hamilton AS, et al. Urinary and sexual function after radical prostatectomy for clinically localized prostate cancer: the Prostate Cancer Outcomes Study. JAMA 2000;283:354-360.
Shipley WU, Thames HD, Sandler HM, et al. Radiation therapy for clinically localized prostate cancer: a multi-institutional pooled analysis. JAMA 1999;281:1598-1604.
Michalski JM, Purdy JA, Winter K, et al. Preliminary report of toxicity following 3D radiation therapy for prostate cancer on 3DOG/RTOG 9406. Int J Radiat Oncol Biol Phys 2000;46:391-402.
Hanlon AL, Watkins Bruner D, Peter R, Hanks GE. Quality of life study in prostate cancer patients treated with three-dimensional conformal radiation therapy: comparing late bowel and bladder quality of life symptoms to that of the normal population. Int J Radiat Oncol Biol Phys 2001;49:51-59.
Kuban DA, Thomas HD, Levy LB, et al. Long-term multi-institutional analysis of stage T1-T2 prostate cancer treated with radiotherapy in the PSA era. Int J Radiat Oncol Biol Phys 2003;57:915-928.
Pollack A, Zagars GK, Smith LG, et al. Preliminary results of a randomized radiotherapy dose-escalation study comparing 70 Gy with 78 Gy for prostate cancer. J Clin Oncol 2000;18:3904-3911.
Pilepich MV, Winter K, John MJ, et al. Phase III Radiation Therapy Oncology Group (RTOG) trial 86-10 of androgen deprivation adjuvant to radiotherapy in locally advanced carcinoma of the prostate. Int J Radiat Oncol Biol Phys 2001;50:1243-1252.
Yock TI, Zietman AL, Shipley WU, Thakral HK, Coen JJ. Long-term durability of PSA failure-free survival after radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 2002;54:420-426.
Fowler FJ Jr, McNaughton Collins M, Albertsen PC, Zietman AL, Elliott DB, Barry MJ. Comparison of recommendations by urologists and radiation oncologists for treatment of clinically localized prostate cancer. JAMA 2000;283:3217-3222.
Sands ME, Pollack A, Zagars GK. Influence of radiotherapy on node-positive prostate cancer treated with androgen ablation. Int J Radiat Oncol Biol Phys 1995;31:13-19.
Morris AD, Zietman AL, Althausen AF, Kaufman DS, Shipley WU. The value of external beam radiation in node positive prostate cancer. Urol Oncol 2001;6:255-260.
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Tannock IF, Osoba D, Stockler MR, et al. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol 1996;14:1756-1764.
Hudes GR, Nathan F, Khater C, et al. Phase II trial of 96-hour paclitaxel plus oral estramustine phosphate in metastatic hormone-refractory prostate cancer. J Clin Oncol 1997;15:3156-3163.
Petrylak DP, Macarthur RB, O'Connor J, et al. Phase I trial of docetaxel with estramustine in androgen-independent prostate cancer. J Clin Oncol 1999;17:958-967.
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Messing EM, Manola J, Sarosdy M, Wilding G, Crawford ED, Trump D. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med 1999;341:1781-1788.
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A 63-year-old man was evaluated in the clinic because of metastatic prostate cancer that was no longer responding to hormone therapy.
The patient had been well until eight years before he came to the clinic, when he had noticed a decreased urinary stream and urinary hesitancy. A test for prostate-specific antigen (PSA) six months later showed a level of 2.7 ng per milliliter; six months after that, the PSA level was 7.7 ng per milliliter. A transrectal needle biopsy of the prostate showed adenocarcinoma, Gleason grade 3 to 4 (on a scale of 1 to 5, with 1 indicating low-grade carcinoma, and 5 high-grade carcinoma), involving all the biopsy cores (Figure 1A and Figure 1B). Computed tomographic (CT) scans of the abdomen and pelvis and a bone scan showed no abnormalities. The general physical examination also showed no abnormalities. Rectal examination revealed a firm, nodular area, 2 to 3 cm in diameter, that involved the left lobe of the prostate and that appeared to go to the edge of the gland. The right lobe was diffusely firm. Laboratory studies and chest radiographic studies showed no abnormalities.
Figure 1. Biopsy Specimens of the Prostate and a Paraaortic Lymph Node (Hematoxylin and Eosin Stains).
The initial, diagnostic biopsy specimen obtained contains extensive adenocarcinoma with several patterns (Panel A, x31). A large glandular pattern and a focal cribriform pattern, graded as Gleason 3C/5 was prominent, but there were also small fused glands (Gleason grade 4/5) (Panel B, x250), for a Gleason score of 7/10. The lymph-node biopsy specimen obtained at laparotomy (Panel C, x31) contains a large nodule (Gleason grade 4/5 adenocarcinoma) with a fused glandular pattern, similar to that seen in some areas of the prostate.
Two months later, the patient was taken to the operating room for a radical prostatectomy. On intraoperative examination of specimens obtained by bilateral pelvic lymph-node biopsy, involvement by metastatic prostate cancer was grossly evident (Figure 1C). The procedure was terminated, and the prostatectomy was not performed. After the operation, the patient's disease was staged as T2N2M0 (a tumor that is palpable or visible on ultrasound, involves both lobes, is associated with more than one positive regional lymph node, and is not accompanied by distant metastases). He was discharged, and treatment with flutamide at a dose of 250 mg three times daily was prescribed. Two months later, the patient's PSA level was 1.1 ng per milliliter. External-beam radiation treatments were administered, with a total dose of 69.4 Gy, and were completed six months after the initial diagnosis.
At that time, the patient's PSA level was 0.5 ng per milliliter, and it remained at or below that level for the next six years while he continued taking flutamide. Magnetic resonance imaging (MRI) of the lumbar spine that was performed four years after the diagnosis showed no abnormalities, and the results of all liver-function tests were normal. Five and a half years after the diagnosis, a bone scan showed no abnormalities. Six years after the diagnosis, the patient's PSA level was 0.2 ng per milliliter.
Eleven months later, the PSA level was 0.9 ng per milliliter; one month after that (seven years after the initial diagnosis), it was 1.4 ng per milliliter. The daily flutamide treatment was discontinued. One month later, a bone scan showed increased uptake at the T11 vertebra, which was suggestive of metastatic disease, but an MRI scan showed no abnormalities. Over the next five months, the patient's PSA level rose to 4.0 and then to 6.6 ng per milliliter. An abdominopelvic CT scan showed newly enlarged retroperitoneal lymph nodes, which were thought to represent metastatic disease. A bone scan showed no metastatic disease.
One month later, leuprolide by intramuscular injection was begun at an initial dose of 7.5 mg, followed one month later by 22.5 mg, which was then given every three months. Four months later, the PSA level was 6.4 ng per milliliter. A bone scan obtained one month later showed metastatic disease at T10, L5, the right humerus, and the ribs bilaterally (Figure 2A). An abdominopelvic CT scan obtained the same day showed progression of the retroperitoneal lymphadenopathy and a newly enlarged lymph node in the right retrocrural area (Figure 3A). A CT scan of the chest showed multiple pulmonary nodules and mediastinal and left hilar lymphadenopathy, which were thought to represent metastatic disease (Figure 4A).
Figure 2. Bone Scans Obtained before and after Chemotherapy.
A scan obtained 7 years and 10 months after the diagnosis (Panel A) reveals metastatic lesions (arrows) in the lower thoracic and lumbar spine. Seven weeks after the initiation of chemotherapy (Panel B), the lesions show increased activity (arrows). This "flare" phenomenon results from an increase in osteoblastic activity in healing bone lesions.
Figure 3. Axial CT Images of the Abdomen Obtained after the Intravenous Administration of Contrast Material.
A CT image obtained 7 years and 10 months after the diagnosis reveals an enlarged lymph node close to the aortic bifurcation (Panel A, arrow). An image from a repeated CT scan obtained at the same level seven weeks after the initiation of chemotherapy shows diminution in the size of the pelvic lymph node (Panel B, arrow).
Figure 4. Axial CT Images of the Chest Obtained after the Intravenous Administration of Contrast Material.
An image obtained seven years and eight months after the diagnosis shows multiple nodules in both lungs (Panel A, arrows). An image obtained seven weeks after the initiation of chemotherapy shows a decrease in size and cavitation of some of the nodules (Panel B, arrows).
Discussion of Management
Dr. Donald S. Kaufman: Over a span of eight years, this man has been cared for by urologists, radiation oncologists, and medical oncologists, and his care has included prostate biopsies, an exploratory laparotomy, radiation treatment, and hormone therapy. Each of these treatment decisions required a risk–benefit analysis, from his initial presentation with an elevated PSA level, when the primary treatments considered included radical prostatectomy and intensive radiation treatment, to his current evaluation, when a decision about the use of chemotherapy had to be made in the context of widespread disease.
Dr. Young, would you show us the slides of the specimens from the initial prostate biopsy?
Dr. Robert H. Young: Most of the cores were extensively involved by adenocarcinoma, even more extensively on the left side than on the right side. The pattern was not that of the usual small acinar adenocarcinoma that is seen in 80 to 90 percent of prostate cancers, but rather a pattern of larger glands. Some areas were well differentiated and were classified as Gleason grade 2, and some were Gleason grade 3C, with a cribriform pattern (Figure 1A). Some clinicians believe that Gleason grade 3 carcinomas with a cribriform pattern have a somewhat worse prognosis than Gleason grade 3 adenocarcinomas without a cribriform pattern. In other areas, there were fused small glands in a packed, microacinar pattern typical of a Gleason grade 4 adenocarcinoma (Figure 1B). The Gleason score, as opposed to grade, was 7 (the sum of the two highest grades, in this case 3 and 4).
Management of Localized Prostate Cancer
Dr. Kaufman: At the time of his initial presentation, the patient appeared to have cancer localized to the prostate. The treatment options included radical prostatectomy and radiation therapy. I would like to ask Drs. McDougal and Shipley to discuss the roles of radical prostatectomy and radiation therapy in the curative treatment of this patient.
Radical Prostatectomy
Dr. W. Scott McDougal: Radical prostatectomy has several advantages: examination of the specimen offers definitive knowledge of the pathological stage and grade of the disease, and the patient benefits from what I consider the most durable method of disease eradication over the long term. Patients may be stratified according to the pathological stage of their disease. If the Gleason score is 2 to 4 and the clinical stage is T1c (i.e., the patient has an elevated PSA level without a palpable mass), the progression-free survival rate after a radical prostatectomy is approximately 90 percent; if the Gleason score is 5 to 6, the rate is about 80 percent; if the score is 7, the rate is about 55 percent; and if the score is 8 to 10, the rate is less than 20 percent.1 For patients who have T2 disease, such as the patient under discussion, the probability of 15 years of progression-free survival is approximately 69 percent. The higher the Gleason score, and the more extensive the disease, the greater the likelihood of intraoperative and postoperative complications. Intraoperative complications include bleeding and injury to the obturator nerve, the urethra, the rectum, or a major pelvic artery or vein. Postoperative complications may substantially alter the patient's quality of life; they fall into three categories: incontinence, impotence, and urethrovesical stricture.
The incidence of complications reported by primary caregivers in single-institution studies tends to reflect better results than the incidence reported by investigators who are not the primary caregivers in large, multi-institution studies. The incidence of urethrovesical stricture, for example, varies from less than 1 percent to 9 percent. The incidence of incontinence in single-institution studies is about 8 percent, with 6 percent of the patients having stress incontinence and 2 percent wearing more than one pad a day. In assessments of incontinence in multi-institutional studies one year after the surgery, about one third of the patients are reported to wear a pad.2 Potency rates also vary, depending on who asks the question of the patient, the age of the patient, and the patient's erectile status before the operation. In studies in which the patient's own assessment is used, potency rates vary from 90 percent in patients less than 50 years of age to 25 percent in those greater than 70 years of age.3 However, when patients are assessed with the use of appropriate outcome measures by a disinterested third party in multi-institutional studies, only 31 percent of patients report that they have an erection and only 9 percent report successful intercourse.2 In a population-based study of 1291 men who were evaluated 18 or more months after radical prostatectomy, 8 percent were incontinent and 60 percent were impotent.4
This patient was thus a good candidate for radical prostatectomy, and at the age of 55 years, he had a low risk of side effects.
Radiation Therapy
Dr. William U. Shipley (Radiation Oncology): The advantages of external-beam radiation therapy as the primary treatment for this patient with localized prostate cancer are that it poses a very low risk of urinary incontinence and stricture; it may eradicate extensions of the tumor beyond the capsule of the prostate; and when it is combined with hormonal therapy, it may offer a chance of cure for some patients, such as this one, with intermediate-risk tumors. The disadvantages of radiation therapy are that the treatment is long, eight to nine weeks; a three-dimensional, conformal technique that allows the delivery of doses of at least 72 Gy may be required; and the treatment adds a low risk of subsequent rectal symptoms. In addition, this therapeutic method does not inform the clinician about possible metastases to lymph nodes, and the long-term sequelae of ultra–high-dose radiation treatments are not known.
The chance of recurrence-free survival after irradiation, with the use of post-treatment PSA level as the monitoring criterion, can be predicted by the risk group of the patient at presentation. For patients with low-risk tumors (stage T1c, a Gleason score of 6 or less, and a PSA level of 10 ng per milliliter or less), the rate is 70 to 80 percent.5 This patient had an intermediate-risk tumor (stage T2 tumor, Gleason score 7, and an initial PSA level of 10 to 20 ng per milliliter), and his expected chance of survival would range from 50 to 55 percent if he were given conventional external-beam radiation therapy alone.
Over the past decade, the development of three-dimensional conformal therapy, which uses computer software to integrate CT images of the patient's internal anatomy in the treatment position, has allowed the volume of tissue to which a high dose of radiation is delivered to conform more exactly to the shape of the tumor. This advance has reduced the incidence of both early and late toxic effects on normal tissue in patients with prostate cancer and allows higher cumulative doses to be delivered with a reduced risk of late effects.6,7 There is now evidence from both randomized and nonrandomized clinical trials of significant improvement in the rates of recurrence-free survival in patients with intermediate-risk tumors when doses greater than 70 Gy are used.8,9,10 In addition, patients who have intermediate-risk tumors have significantly higher disease-specific survival rates with a short course of neoadjuvant androgen-suppression therapy and radiation treatment than they do with radiation treatment alone.10
Thus, the current recommendation for this patient would be irradiation to a total dose of 75 to 76 Gy by the three-dimensional conformal technique, preceded by a short course of neoadjuvant androgen suppression. In recent reports, the rates of disease progression 6 to 10 years after irradiation are similar to those in reports of series of patients undergoing prostatectomy.8,11
Strict contraindications to external-beam radiation therapy include prior pelvic irradiation, active inflammatory bowel disease, a permanent Foley catheter, and morbid obesity. For this patient, who had none of these problems, radiation therapy is a reasonable alternative to radical prostatectomy.
Dr. Kaufman: Both radical prostatectomy and conformal external-beam radiation treatment can cure localized prostate cancer; cure is more likely for patients with low-risk disease than for patients in the intermediate-risk and high-risk groups. The incidence of serious incontinence after radical prostatectomy is about 5 percent when the procedure is performed by experienced surgeons and virtually nonexistent after radiation treatment; the rate of impotence is about 50 percent after either treatment. Not surprisingly, surgeons prefer prostatectomy and radiation oncologists favor irradiation as the treatment of choice.12 No prospective comparative study of conformal external-beam radiation treatment with higher total doses of radiation and surgery has been reported.
After consultation with his physicians, this patient chose to undergo radical prostatectomy. At laparotomy, enlarged pelvic lymph nodes were seen. Dr. Young, would you describe the specimens for us?
Dr. Young: On intraoperative gross examination, the three right obturator lymph nodes sampled were rubbery in texture and ranged from 0.5 to 2.0 cm in greatest dimension; the single left obturator lymph node was 1.4 cm in its greatest dimension and contained a nodule of firm, tan-to-white tissue, a finding indicating the presence of tumor. On microscopical examination of both frozen and permanent sections (Figure 1C), the tumor had a small, acinar, fused glandular pattern similar to that seen in the prostate biopsy specimen. Two of the three lymph nodes on the right side and the one on the left side contained cancer.
Management of Locally Advanced Prostate Cancer
Dr. Kaufman: Dr. Gomery, you were the surgeon caring for this patient. Please tell us what you did and the reasons for your decisions.
Dr. Pablo Gomery (Urology): Because the biopsy had revealed a rather poorly differentiated prostatic carcinoma and examination of several lymph nodes had shown grossly evident carcinoma, I believed that the likelihood of a cure for this patient by prostatectomy was low and did not justify the potential complications of the operation in a man of his age who was sexually active, so I terminated the procedure without completing the prostatectomy.
Dr. Kaufman: Dr. Zietman, what is the role of radiation treatment in this patient, who had positive nodes and in whom surgery was aborted?
Radiation Therapy
Dr. Anthony L. Zietman: More than 90 percent of patients who have node-positive prostate cancer have occult metastatic disease elsewhere. As a consequence, cure is unlikely with any localized therapy. Many patients, however, have bulky or aggressive disease at the primary site, which may cause local symptoms and may be the first site of tumor progression. Two studies, one from the M.D. Anderson Cancer Center13 and one from this institution,14 found that in patients treated with androgen deprivation alone, the primary site was the most common first site of progression, requiring subsequent local therapy in up to 73 percent of the patients. In contrast, of the patients treated with both androgen deprivation and local therapy (radiation therapy or transurethral prostatectomy), local recurrence of disease requiring therapy developed in 11 percent or less.
Local therapy plus androgen deprivation may therefore be justified to extend the initial disease-free interval and to reduce symptomatic local progression. In this patient, I recommended radiation therapy; this was before the days of three-dimensional conformal treatment, and he received what was then our standard dose — approximately 69 Gy.
Dr. McDougal: The fact that you treated him locally does not necessarily mean that you eradicated the local disease or eliminated the possibility of local progression.
Dr. Zietman: Absolutely not.
Dr. Kaufman: The patient did not experience any local side effects from the radiation therapy, and he stated that his sexual potency was unaffected. He was free of symptoms for seven years after the diagnosis; then, while he was receiving flutamide, the PSA level rose to 0.9 ng per milliliter and then to 1.4 ng per milliliter. The flutamide was discontinued. Intramuscular leuprolide was begun six months later, but the PSA level continued to rise. A bone scan and chest and abdominal CT scans were obtained four months later.
Dr. Mukesh G. Harisinghani: The bone scan at this time (Figure 2A) shows areas of increased uptake in T10, the ribs bilaterally, and the right humerus. Images from a contrast-enhanced CT scan of the abdomen and pelvis (Figure 3A) show newly enlarged retroperitoneal lymph nodes adjacent to the upper and lower abdominal aorta and the bifurcation — a finding that probably represents metastatic disease. The lung windows from the chest CT scan (Figure 4A) show multiple nodules in both lungs, and the mediastinal windows show enlarged precarinal and subcarinal lymph nodes; all of these findings almost certainly represent metastatic disease.
Dr. Kaufman: What are the treatment options at this point? The patient has been receiving leuprolide for four months, with no improvement. Dr. Smith, would you discuss hormone treatment for advanced prostate cancer?
Hormonal Therapy
Dr. Matthew R. Smith (Hematology/Oncology): Androgen-deprivation therapy by either bilateral orchiectomy or administration of a gonadotropin-releasing hormone agonist such as leuprolide is the mainstay of treatment for advanced or metastatic prostate cancer. Androgen-deprivation therapy by either method decreases serum testosterone levels by more than 95 percent and leads to objective responses in the majority of patients. Monotherapy with antiandrogens is an alternative to standard androgen-deprivation therapy. Flutamide is a nonsteroidal antiandrogen that blocks the action of testosterone by binding to the androgen receptor in target tissue. This man's disease responded to flutamide monotherapy for more than six years. About two thirds of men with progressive disease who receive antiandrogen monotherapy will respond to subsequent androgen-deprivation therapy. The long duration of the response to flutamide monotherapy in this case suggests a higher-than-average chance of a response to subsequent medical or surgical castration. In addition, in a few men treated with a gonadotropin-releasing hormone agonist, testosterone levels approaching those achieved by bilateral orchiectomy are not reached. I recommend the measurement of serum-testosterone levels for patients who either do not have a response or who have unexpectedly short responses to a gonadotropin-releasing hormone agonist. Bilateral orchiectomy may prove effective in the men whose testosterone production cannot be adequately suppressed with a gonadotropin-releasing hormone agonist.
Dr. Kaufman: Given the patient's progression of disease while he was receiving hormonal treatment, we considered multiagent chemotherapy. Dr. Michaelson, would you discuss the role of chemotherapy in the treatment of a patient, such as this one, who has advanced, hormone-refractory prostate cancer?
Chemotherapy
Dr. M. Dror Michaelson (Hematology/Oncology): The early experience with cytotoxic chemotherapy in prostate cancer was largely unsuccessful, and until the 1990s, chemotherapy was not considered a standard treatment for this disease. Two randomized, phase 3 studies in the mid-1990s showed a benefit with mitoxantrone and corticosteroids as compared with corticosteroids alone, with improvement in the patients' scores on pain scales and in their overall quality of life.15,16 However, even this combination produced a decrease in the PSA level in only 30 to 35 percent of the patients. The same studies also failed to show a benefit in overall or disease-specific survival among patients treated with mitoxantrone and corticosteroids as compared with those treated with corticosteroids alone.
Taxane-based regimens have now been studied in numerous phase 1 and 2 clinical trials, and they appear to be more promising than previously studied therapies. Paclitaxel and docetaxel alone or in combination with estramustine, with or without carboplatin and etoposide, have been studied in multiple phase 1 and 2 trials. Many of these trials have documented response rates in excess of 50 percent.17,18 In response to these data, an Intergroup phase 3 study comparing docetaxel and estramustine with the current standard therapy, mitoxantrone plus corticosteroids, is under way.
In the past few years, clinical trials have evaluated the usefulness of adding a third agent to the combination of docetaxel and estramustine. These have included biologic agents targeted against growth-factor pathways and traditional cytotoxic chemotherapy drugs. At this hospital, my colleagues and I have conducted a study of a regimen that combines docetaxel, estramustine, and carboplatin in men with hormone-refractory prostate cancer. Accrual to this study has been completed, but the results are not yet available. The patient under discussion was enrolled in this trial.
Dr. Kaufman: Eight years after the initial diagnosis, chemotherapy consisting of docetaxel, estramustine, and carboplatin was initiated, carried out for six cycles, and completed in six months. During the six months of chemotherapy, the patient had virtually no symptoms except for very mild fatigue. He did not miss work and was able to continue his activity of mountain climbing. His PSA level dropped to 0.5 ng per milliliter shortly after the start of chemotherapy, and at the completion of chemotherapy his PSA level was less than 0.2 ng per milliliter.
Dr. Harisinghani, would you show us the images that were obtained after the treatment?
Dr. Harisinghani: On the bone scan obtained seven weeks after the start of chemotherapy (Figure 2B), the preexisting lesions all showed increased activity. This phenomenon, which has been called a flare, represents increased osteoblastic activity within the metastases, which is a sign of improvement after treatment. No new lesions were identified. The paraaortic lymphadenopathy has regressed in size as compared with that seen on the previous abdominal CT scan (Figure 3B). A chest CT scan obtained at the same time reveals that the pulmonary nodules have regressed in size (Figure 4B) and show some cavitation, indicating a response to therapy. The mediastinal nodes have all decreased in size.
Dr. Kaufman: These images illustrate an important point. When the patient's chest and abdominal CT scans showed that there had been dramatic improvement, the bone scan was initially read as revealing an increase in metastatic disease. On review, however, it became clear that this finding was a flare reaction — all of the increased uptake was in areas that had previously been involved by tumor. This is a rare phenomenon that occurs as a result of treatment, and it is important to recognize.
Unfortunately, four months after the completion of chemotherapy, the patient's PSA level began to rise, and three months later — nine years after the initial diagnosis and one year after the initiation of chemotherapy — it was 6.3 ng per milliliter. Repeated CT scans revealed stable lung nodules. An abdominopelvic CT scan showed an increase in the size of the left paraaortic lymph nodes. A bone scan showed a new lesion in the T9 vertebral body and a lesion in T10 that had increased in size.
Because of his good response and because he did not have a toxic reaction to the chemotherapy regimen, we decided to treat him again, using the same agents. At the time of the first chemotherapy visit, he reported smoky vision in his left eye, with no gait disturbance or headaches. He was evaluated by a vitreoretinal specialist, who conducted fluorescein testing, indocyanine green angiography, and optical coherence tomography; a 1-mm area of thickening was observed, a finding consistent with a single choroidal metastatic lesion on the left retina. After one cycle of chemotherapy, the patient noted an improvement in visual clarity. His PSA level decreased from 6.0 to 3.0 ng per milliliter after the first cycle of chemotherapy; after seven cycles, his PSA level was less than 0.2 ng per milliliter.
Dr. Alex F. Althausen (Urology): What is the average duration of tumor-free survival for a patient who presents with known nodal disease and is given all these therapies? Is this patient's course unusual in being protracted over nine years? Or, can we tell patients that even if the results of an MRI or CT scan are positive for cancer, with appropriate chemotherapy they can expect nine or more years of a reasonable quality of life?
Dr. James Talcott (Medical Oncology): This patient's long survival is unusual, but the course of prostate cancer is highly variable, even after adjustments for tumor stage, Gleason score, and PSA level. Earlier diagnosis as a result of PSA screening has led to a longer survival for all patients, through "stage migration."19 In a small, randomized trial of immediate hormone treatment as compared with treatment at the time of clinical relapse in patients, such as this man, with positive nodes, survival was improved in the immediate-treatment group,20 but growing evidence of toxicity from long-term androgen-deprivation therapy suggests that discussion should precede chemical castration of asymptomatic men without metastases.21
Dr. Kaufman: At the most recent follow-up, the patient's PSA level was 0.2 ng per milliliter. A bone scan and abdominal, pelvic, and chest CT scans all showed stable disease. Unfortunately, his eye lesion recently recurred, and he is now receiving proton-beam therapy to the eye. In the care of this patient over what is now a 10-year span, we have used almost every known treatment for prostate cancer. Remarkably, the patient has felt well throughout the entire course of his illness, carrying on with his normal occupation and activities.
Anatomical Diagnosis
Adenocarcinoma of the prostate with metastases.
Source Information
From the Division of Medical Oncology, Department of Medicine (D.S.K.), and the Departments of Urology (W.S.M.), Radiation Oncology (A.L.Z.), Radiology (M.G.H.), and Pathology (R.H.Y.), Massachusetts General Hospital; and the Departments of Medicine (D.S.K.), Urology (W.S.M.), Radiation Oncology (A.L.Z.), Radiology (M.G.H.), and Pathology (R.H.Y.), Harvard Medical School.
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