Proton therapy of prostate cancer by anterior-oblique beams: implications of setup and anatomy variations.

Proton therapy of prostate by anterior beams could offer an attractive option for treating patients with hip prosthesis and limiting the high-dose exposure to the rectum. We investigated the impact of setup and anatomy variations on the anterior-oblique (AO) proton plan dose, and strategies to manage these effects via range verification and adaptive delivery. Ten patients treated by bilateral (BL) passive-scattering proton therapy (79.2 Gy in 44 fractions) who underwent weekly verification CT scans were selected. Plans with AO beams were additionally created. To isolate the effect of daily variations, initial AO plans did not include range uncertainty margins. The use of fixed planning margins and adaptive range adjustments to manage these effects was investigated. For each case, the planned dose was recalculated on weekly CTs, and accumulated on the simulation CT using deformable registration to approximate the delivered dose. Planned and accumulated doses were compared for each scenario to quantify dose deviations induced by variations. The possibility of estimating the necessary range adjustments before each treatment was explored by simulating the procedure of a diode-based in vivo range verification technique, which would potentially be used clinically. The average planned rectum, penile bulb and femoral heads mean doses were smaller for initial AO compared to BL plans (by 8.3, 16.1 and 25.9 Gy, respectively). After considering interfractional variations in AO plans, the target coverage was substantially reduced. The maximum reduction of V 79.2/D 95/D mean/EUD for AO (without distal margins) (25.3%/10.7/1.6/4.9 Gy, respectively) was considerably larger than BL plans. The loss of coverage was mainly related to changes in water equivalent path length of the prostate after fiducial-based setup, caused by discrepancies in patient anterior surface and bony-anatomy alignment. Target coverage was recovered partially when using fixed planning margins, and fully when applying adaptive range adjustments. The accumulated organs-at-risk dose for AO beams after range adjustment demonstrated full sparing of femoral heads and superior sparing of penile bulb and rectum compared to the conventional BL cases. Our study indicates that using AO beams makes prostate treatment more susceptible to target underdose induced by interfractional variations. Adaptive range verification/adjustment may facilitate the use of anterior beam approaches, and ensure adequate target coverage in every fraction of the treatment.

Proton beam therapy and localised prostate cancer: current status and controversies.

Proton therapy is a promising, but costly, treatment for prostate cancer. Theoretical physical advantages exist; yet to date, it has been shown only to be comparably safe and effective when compared with the alternatives and not necessarily superior. If clinically meaningful benefits do exist for patients, more rigorous study will be needed to detect them and society will require this to justify the investment of time and money. New technical advances in proton beam delivery coupled with shortened overall treatment times and declining device costs have the potential to make this a more cost-effective therapy in the years ahead.

Selective bladder preservation for muscle-invasive transitional cell carcinoma of the urinary bladder.

Invasive transitional cell carcinoma (TCC) of the urinary bladder is traditionally treated with radical cystectomy. This approach results in great morbidity and lifestyle changes, and approximately half of the patients treated in this way will experience recurrent TCC despite surgery. An alternative approach using selective bladder-preservation techniques incorporates transurethral resection of bladder tumours, radiation therapy, and chemotherapy. Over the past 20 years, international experience has demonstrated that this approach is feasible, safe, and well tolerated. Furthermore, the long-term outcomes of overall survival and disease-free survival compare favourably with the outcomes from radical cystectomy. The most important predictor of response is stage, with significantly higher long-term survival in patients with T2 disease. Another important positive predictor of complete response to therapy is the ability of the urologic oncologist to remove all visible tumour through a transurethral approach prior to initiation of radiation therapy. A negative predictive factor is the presence of hydronephrosis, and age and gender do not affect disease-free survival. The majority of patients who enjoy long-term survival do so with an intact native bladder. Quality of life studies have demonstrated that the retained bladder functions well in nearly all of these patients. Selective bladder preservation will not entirely take the place of radical cystectomy, but should be offered as an important alternative to patients newly diagnosed with muscle-invasive TCC.

10-year outcome for men with localized prostate cancer treated with external radiation therapy: results of a cohort study.

PURPOSE: We determine the efficacy of conventional dose, external beam radiation for localized prostate cancer using cohort analysis with maximized followup. MATERIALS AND METHODS: A total of 205 men with T1-2 prostate cancer were treated with conventional external beam radiation to a median and modal dose of 68.4 Gy during a 16-month period from 1991 to 1993. Followup was maximized in these patients, and median followup for those alive with or without disease was 114 months. RESULTS: Median patient age at treatment was 72 years, and overall survival at 5 and 10 years was 78% and 53%, respectively. The actuarial risk of local failure was 18% at 10 years as was the risk of metastatic disease. The actuarial risk of being free of biochemical failure at 10 years (American Society for Therapeutic Radiology and Oncology definition) was 49%. That risk was 42% if the definition was used without backdating failure to a time between last low value and first increase. When a crude analysis of 10-year outcome was performed 127 of the 205 treated patients (62%) were still alive, including 59% with no evidence of biochemical failure and a median prostate specific antigen of 1.0 ng/ml. Of the 78 men (38% of total) who died during the 10 years 32 died either of or with recurrent cancer. CONCLUSIONS: Mature followup minimizes many of the biases seen in previously published radiation series. This study provides a yardstick against which newer radiation modalities may be measured.

Corticosteroid use after prostate brachytherapy reduces the risk of acute urinary retention.

OBJECTIVES: To evaluate the role of short-term steroids after prostate brachytherapy to reduce oedema and thus the risk of urinary retention associated with brachytherapy, as this can require surgical intervention and may even result in incontinence. PATIENTS AND METHODS: A retrospective review was conducted on 400 consecutive patients with early-stage prostate cancer who underwent ultrasonography-guided transperineal brachytherapy. Androgen deprivation was given to 146 patients for 3 months before the implant and 280 received a 2-week course of dexamethasone (4 mg twice daily for 1 week then 2 mg twice daily). Forty-five patients developed acute urinary retention at a median of 12 days after implantation. Univariate and multivariate analyses were used to evaluate the potential risk factors for urinary retention. RESULTS: Acute urinary retention developed in 11.1% of the patients and the risk was predicted by increasing prostate volume at the time of diagnosis. This risk was higher (18.8%) for men receiving no dexamethasone and lower (8.2%) for those who did. In the multivariate analysis the volume at diagnosis and the use of dexamethasone remained significant. The use of steroids counterbalanced the effect of increasing prostate volume on the incidence of retention. The risk of retention was higher in those men receiving androgen deprivation to shrink their prostates than in those whose prostates were of suitable size for implantation at the time of diagnosis. CONCLUSION: Reducing prostate volume by androgen deprivation before brachytherapy may be less important in preventing brachytherapy-related urinary retention than the use of corticosteroids to reduce oedema afterward.

Selective bladder preservation by combined modality protocol treatment: long-term outcomes of 190 patients with invasive bladder cancer.

OBJECTIVES: To evaluate the outcomes of patients with muscle-invasive Stage T2-4a bladder carcinoma managed by transurethral surgery and concurrent chemoradiation. METHODS: A total of 190 patients were treated on institutional prospective protocols using concurrent cisplatin-containing chemotherapy and radiotherapy after rigorous transurethral resection of the bladder tumor. Patients were re-evaluated by repeated biopsy and urine cytologic analysis after 40 Gy, with the initial tumor response guiding subsequent therapy. One hundred twenty-one patients with a complete response by cytologic and histologic examination and those medically unfit for cystectomy received boost chemoradiation to 64 to 65 Gy. Those patients without a complete response were advised to undergo radical cystectomy. A total of 66 patients (35%) ultimately underwent radical cystectomy; 41 for less than a complete response and an additional 25 for recurrent invasive tumors. The median follow-up was 6.7 years for all surviving patients. RESULTS: The 5 and 10-year actuarial overall survival rate was 54% and 36%, respectively (Stage T2, 62% and 41%; Stage T3-T4a, 47% and 31%, respectively). The 5 and 10-year disease-specific survival rate was 63% and 59% (Stage T2, 74% and 66%; Stage T3-T4a, 53% and 52%), respectively. The 5 and 10-year disease-specific survival rate for patients with an intact bladder was 46% and 45% (Stage T2, 57% and 50%; Stage T3-T4a, 35% and 34%), respectively. The pelvic failure rate was 8.4%. No patient required cystectomy because of bladder morbidity. CONCLUSIONS: The 10-year overall survival and disease-specific survival rates are comparable with the results reported for contemporary radical cystectomy for patients of similar clinical and pathologic stage. One third of patients treated on protocol with the goal of bladder sparing ultimately required a cystectomy. A trimodality approach with bladder preservation based on the initial tumor response is, therefore, safe, with most long-term survivors retaining functional bladders.

Late normal tissue sequelae in the second decade after high dose radiation therapy with combined photons and conformal protons for locally advanced prostate cancer.

PURPOSE: We determined the long-term normal tissue effects of 77.4 Gy. delivered to the prostate in patients with locally advanced prostate cancer. METHODS AND MATERIALS: Between 1976 and 1992, 167 men with stages T3 to 4 prostate cancer were treated on protocol with 50.4 Gy. photons at 1.8 Gy. per fraction using a 4-field box arrangement, followed by a conformal perineal proton boost of 27 Gy. (cobalt Gy. equivalent) in 11 fractions. The chart was reviewed and 39 of the 42 surviving patients were interviewed. Median followup was 13.1 years (range 7 to 23). Normal tissue morbidity was recorded using Radiation Therapy Oncology Group criteria and the late effects normal tissue scale. RESULTS: The actuarial incidence of grade 2 or greater genitourinary morbidity was 59% at 15 years. However, these grade 2 or greater problems persisted to the time of the interview in only 7 of 39 cases. The actuarial incidence of grade 2 or greater hematuria was 21% at 5 years and 47% at 15. For grade 3 or greater hematuria the risk was 3% and 8% at 5 and 15 years, respectively. No patient required cystectomy but 1 required diversion for morbidity. Urethral stricture and urinary incontinence with pads needed developed in 4 and 3 men, respectively. This particular morbidity was strongly associated with previous or subsequent prostate surgery. The actuarial incidence of grade 2 or greater gastrointestinal morbidity was 13% at 5 and 15 years, while grade 1 rectal bleeding occurred in another 41%. CONCLUSIONS: High dose conformal radiation to the prostate is followed by a high rate of low grade rectal bleeding but a low rate of grade 2 or higher gastrointestinal morbidity. This rate is stable and does not increase beyond 5 years. Genitourinary morbidity continues to develop well into the second decade after treatment, although high grade morbidity is uncommon. These findings do not suggest that the modern trend toward high dose prostate treatment with conformal techniques will result in a high incidence of serious and permanent late sequelae but it appears that hematuria will be common.

Conservative management of prostate cancer in the prostate specific antigen era: the incidence and time course of subsequent therapy.

PURPOSE: The long natural history of early stage prostate cancer is well recognized and a conservative approach to the treatment of elderly men is often encouraged. We assessed the ability of patients and physicians to adhere to a policy of watchful waiting in the prostate specific antigen (PSA) era. MATERIALS AND METHODS: We retrospectively reviewed the records of all 199 men with stages T1-2 prostate cancer and PSA less than 20 ng./ml. who in our practice elected watchful waiting. Median followup in the population overall was 3.4 years. We performed Kaplan-Meier actuarial analysis of overall and disease specific survival, and most pertinent survival free from therapy. A questionnaire was administered to record the attitude of patients who ultimately proceeded to treatment to determine how therapy was triggered. RESULTS: Median patient age was 71 years and median PSA was 6.6 ng./ml. The tumor was impalpable in 52% of patients, Gleason sum was 6 or less in 80% and 11% used some form of herbal remedy or nutritional supplementation. Of the 37 men who died during observation, including 35 of co-morbid illness, only 6 underwent treatment. Overall survival at 5 and 7 years was 77% and 63% but disease specific survival was 98% and 98%, respectively. A total of 64 patients underwent treatment and actuarial freedom from treatment was 56% at 5 years, including 51% and 73% in those younger and older than 75 years at diagnosis. The likelihood of being alive and free from treatment was 43% at 5 years and 26% at 7. Of the 63 men treated 48 (76%) underwent radical therapy (brachytherapy in 17, external beam radiotherapy in 29 and prostatectomy in 2), while only 24% received androgen deprivation. The median PSA increase from diagnosis to treatment in treated patients was 2.9 ng./ml., and it was 0.9 ng./ml. from diagnosis to the last followup in those not treated. Of the treated patients 81% believed that the physician had initiated therapy due to a PSA increase or a nodule. However, physicians recorded having advocated treatment in only 24% of cases. CONCLUSIONS: When patients do not die of co-morbid illness, they are likely to proceed to therapy well within the first decade after diagnosis (57% by 5 years and 74% by 7). Therapy was usually definitive (radical) and triggered by slight, inevitable PSA increases. The patient perception was that the physicians initiated therapy in response to increasing PSA. However, the physicians more often perceived that treatment was initiated by patients. Therefore, watchful waiting in the PSA era often represents radical therapy delayed by a few years.

Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer.

BACKGROUND: Treatment with a gonadotropin-releasing hormone agonist decreases bone mineral density and increases the risk of fracture in men with prostate cancer. We conducted a controlled study of the prevention of osteoporosis in men undergoing treatment with a gonadotropin-releasing hormone agonist. METHODS: In a 48-week, open-label study, we randomly assigned 47 men with advanced or recurrent prostate cancer and no bone metastases to receive either leuprolide alone or leuprolide and pamidronate (60 mg intravenously every 12 weeks). Bone mineral density of the lumbar spine and the proximal femur was measured by dual-energy x-ray absorptiometry. Trabecular bone mineral density of the lumbar spine was measured by quantitative computed tomography. Forty-one men completed the study. RESULTS: In men treated with leuprolide alone, the mean (+/-SE) bone mineral density decreased by 3.3+/-0.7 percent in the lumbar spine, 2.1+/-0.6 percent in the trochanter, and 1.8+/-0.4 percent in the total hip, and the mean trabecular bone mineral density of the lumbar spine decreased by 8.5+/-1.8 percent (P<0.001 for each comparison with the base-line value). In contrast, the mean bone mineral density did not change significantly at any skeletal site in men treated with both leuprolide and pamidronate. There were significant differences between the two groups in the mean changes in bone mineral density at 48 weeks in the lumbar spine (P<0.001), trochanter (P = 0.003), total hip (P=0.005), and trabecular bone of the lumbar spine (P=0.02). CONCLUSIONS: Pamidronate prevents bone loss in the hip and lumbar spine in men receiving treatment for prostate cancer with a gonadotropin-releasing hormone agonist.

Selective bladder conservation using transurethral resection, chemotherapy, and radiation: management and consequences of Ta, T1, and Tis recurrence within the retained bladder.

OBJECTIVES: Although radical cystectomy remains the standard of care for invasive bladder cancer in the United States, many groups are exploring the use of trimodality therapy using transurethral resection of the bladder tumor, radiation, and chemotherapy in an attempt to spare patients the need for cystectomy. As transitional cell carcinoma often arises from a urothelial field change, there is concern that the retained bladder is at risk of subsequent superficial (Ta, T1, Tis) tumors, some of which may have lethal potential. This study reports the outcomes of those patients with superficial relapse of transitional cell carcinoma after trimodality therapy. METHODS: One hundred ninety patients were treated using a series of trimodality therapy protocols between 1986 and 1998. All patients received induction chemotherapy and radiation and were selected for bladder preservation on the basis of a cytologic and histologic complete response. One hundred twenty-one patients had a complete response and formed the subjects of this study. RESULTS: With a median follow-up of 6.7 years for patients still alive, 32 experienced a superficial relapse (26%). The median time to this failure was 2.1 years. Sixty percent of the superficial failures were carcinoma in situ (Tis) and 67% arose at the site of the original invasive tumor. The risk of superficial failure was higher among those who had Tis associated with their original muscle-invasive tumor. Twenty-seven of these 32 cases were managed conservatively with transurethral resection and intravesical therapy. The irradiated bladder tolerated this therapy well and only 3 patients required treatment breaks. The 5 and 8-year survival was comparable for those who experienced superficial failure (68% and 54%, respectively) and those who had no failure at all (n = 74, 69% and 61%, respectively). However, a substantially lower chance of being alive with the native bladder owing to the need for late salvage cystectomies (61% versus 34%) was found. Cystectomy became necessary in 31% (10 of 32) either because of additional superficial recurrence (n = 7) or progression to invasive disease (n = 3). CONCLUSIONS: A trimodality approach to transitional cell bladder cancer mandates lifelong cystoscopic surveillance. Although most completely responding patients retain their bladders free from invasive relapse, one quarter will develop superficial disease. This may be managed in the standard fashion with transurethral resection of the bladder tumor and intravesical therapies but carries an additional risk that late cystectomy will be required.

An organ-preserving approach to muscle-invading transitional cell cancer of the bladder.

Bladder-preserving treatment for muscle-invasive disease is based on the response of the tumor to induction combined modality therapy. In the future, an organ-conserving approach will be widely offered as a safe and reasonable alternative to radical cystectomy.

The case for neoadjuvant androgen suppression before radiation therapy.

Neoadjuvant androgen suppression (NAS) can reduce the number of tumor clonogens prior to radiation, thus increasing the tumor control probability. Also, NAS may sensitize tumor cells to radiation if cell kill by both modalities follows a common pathway. The timing and sequence of NAS and radiation are important, with radiation being most effective if given at the point of maximal tumor regression. The biologic rationale for NAS + radiation has been reinforced by results from randomized trials, in particular RTOG 8610. However, many murine adenocarcinomas respond to androgen deprivation by a reduction in the proliferation rate and arrest in G(0), and in vitro data suggest that this arrest may interfere with radiation-induced cell killing. The mechanism of cell killing after low-dose-rate radiation (brachytherapy) may be different from that after high-dose-rate treatment. There are no reported experimental data assessing the interaction of NAS and brachytherapy to determine whether the combination offers a theoretical advantage or is potentially deleterious. Whether we understand the mechanism or not, clinical trials seem to support a positive interaction of NAS with external-beam radiation, but we have only begun to explore the timing and sequence that will provide the maximal effect. It cannot be assumed that the same advantage will hold with brachytherapy.

Thymosin beta-15 predicts for distant failure in patients with clinically localized prostate cancer-results from a pilot study.

OBJECTIVES: To report the results of a pilot study on the prognostic value of a newly identified actin-binding protein, thymosin beta-15 (Tbeta15), in predicting prostate-specific antigen (PSA) and bone failure in patients with Gleason 6/10 clinically localized prostate cancer. METHODS: Thirty-two patients (median age 70 years) with clinically localized, moderately differentiated (Gleason 6/10) prostate cancer treated by external beam radiotherapy alone (68.4 Gy) with available paraffin blocks at the Massachusetts General Hospital were evaluated for this pilot study. All patients had clinical Stage M0 disease at initial presentation, which was documented by bone scan (T1c-4,NX). Their corresponding biopsy specimens were stained immunohistochemically for Tbeta15, which was then correlated with the clinical outcome in a blinded manner. The median follow-up was 6 years (range 1 to 19) for all of the patients. RESULTS: The outcomes of the 32 patients can be grouped into three categories: patients with no evidence of disease (n = 11), patients with PSA failure without documented bone failure (n = 11), and patients with PSA failure and documented bone failure (n = 10). Tbeta15 staining intensity strongly correlated with clinical outcome. Of those patients whose specimens stained 3+ (strongest staining), 62% developed bone failure compared with 13% of those patients whose specimens stained 1+ (weakest staining) (P = 0.01). The 5-year freedom from PSA failure was only 25% for those patients with 3+ staining compared with 83% for those with 1+ staining (P = 0.02). CONCLUSIONS: The results of this pilot study have demonstrated that Tbeta15 staining intensity may be a potentially important marker to identify high-risk patients with moderately differentiated, clinically localized prostate cancer.

Acute and late toxicity of patients with inflammatory bowel disease undergoing irradiation for abdominal and pelvic neoplasms.

PURPOSE: Little data exists in the medical literature describing the response of patients with inflammatory bowel disease (IBD) to abdominal and pelvic irradiation. To clarify the use of this modality in this setting, this study assesses the short- and long-term tolerance of 28 patients with IBD to abdominal and pelvic irradiation. METHODS AND MATERIALS: From 1970 to 1999, 28 patients with IBD (10 patients-Crohn's disease, 18 patients-ulcerative colitis) were identified and underwent external beam abdominal or pelvic irradiation. Mean follow-up time after radiation therapy was 32 months. Patients were treated either by specialized techniques (16 patients) to minimize small and large bowel irradiation or by more conventional approaches (12 patients). Acute and late toxicity was scored. RESULTS: The overall incidence of severe toxicity was 46% (13/28 patients). Six of 28 patients (21%) experienced severe acute toxicity necessitating cessation of radiation therapy. Late toxicity requiring hospitalization or surgical intervention was observed in 8 of 28 patients (29%). One patient experienced both an acute as well as late toxicity. For patients undergoing radiation therapy by conventional approaches, the 5-year actuarial rate of late toxicity was 73%. This figure was 23% for patients treated by specialized techniques (p = 0.02). CONCLUSIONS: Because of the potentially severe toxicity experienced by patients with IBD undergoing abdominal and pelvic irradiation, judicious use of this modality must be employed. Definition of IBD location and activity as well as careful attention to irradiation technique may allow treatment of these patients with acceptable rates of morbidity.

Organ-conserving approaches to muscle-invasive bladder cancer: future alternatives to radical cystectomy.

In the USA radical surgery remains the golden standard for invasive bladder cancer. Yet in most other areas of surgical oncology the trend of the 1990s has been towards organ conservation with chemoradiation with or without limited local surgery. Patients with breast, oesophageal, anal, lung and larynx cancer are routinely offered conservative therapies as valid options in the management of their diseases but bladder stands apart from the crowd. Evidence is presented here to show that this need not be the case. Four older randomized trials failed to show a survival advantage when immediate cystectomy was compared with radiation followed by salvage cystectomy, if required. Five and 8-year survival rates for clinically staged patients treated by transurethral resection and chemoradiation (trimodality therapy) in several modern, large and mature series show survival rates comparable to those reported in contemporary radical cystectomy series. Eighty per cent of those alive 5 years after chemoradiation still retain their native bladder. Although superficial relapse occurs in 20% of cases, it remains responsive to BCG (Bacilles bilie de Calmette-Guerin) in the manner of de novo superficial disease. Quality-of-life studies show that the retained bladder functions well. At the Massachusetts General Hospital and in the multicentre prospective trials, less than 1% of patients needed cystectomy for bladder morbidity. It is of note that continent diversions may be performed as salvage after contemporary radiation therapy. Trimodality therapy is a novel and contemporary approach that owes little to the radiation treatment offered in the 1970s. While it will never entirely take the place of radical cystectomy, it should be offered as a reasonable alternative to patients with a new diagnosis of bladder cancer. This multidisciplinary approach will allow uro-oncology to keep in step with the oncological vanguard.

An update of combined modality therapy for patients with muscle invading bladder cancer using selective bladder preservation or cystectomy.

PURPOSE: We update the results of tri-modality treatment for patients with muscle invading bladder tumors with selection for bladder preservation based on tumor response to induction therapy. MATERIAL AND METHODS: We reviewed the literature on modern tri-modality bladder preserving approaches using transurethral resection, radiation and concurrent chemotherapy followed by either bladder conservation with careful surveillance for complete responding patients or prompt cystectomy in those whose tumors persist after induction therapy. RESULTS: The published experiences from 3 centers and 2 prospective trials done by the Radiation Therapy Oncology Group were evaluated for 5-year overall survival of patients selected for bladder preservation or prompt cystectomy (49 to 63%) and for those with a conserved bladder (38 to 43%). The overall 5-year survival rates were comparable to other series of immediate cystectomy based approaches in patients of similar age and presenting with tumors of similar clinical stage. Of patients treated with the bladder preserving approach 20 to 30% cured of muscle invading cancer will subsequently have a new superficial tumor. The superficial tumors have responded well to intravesical drug therapy. Modern bladder preserving treatments usually result in a well functioning bladder without incontinence or significant hematuria. However, concurrent systemic chemotherapy and radiation have the potential for acute morbidity. Presently the ideal candidate for bladder preservation has primary clinical stage T2 tumor, no associated ureteral obstruction, visibly complete transurethral resection and complete response after induction chemoradiation based on endoscopic evaluation including re-biopsy and cytology. CONCLUSIONS: It is recommended that tri-modality treatment be administered by dedicated multimodality teams. In this country this approach to treatment is available at many of the institutions participating in the Radiation Therapy Oncology Group study. This treatment may be considered a reasonable alternative in patients who are deemed medically unfit for cystectomy and for those who are seeking an alternative to radical cystectomy.

Radiation therapy for clinically localized prostate cancer: a multi-institutional pooled analysis.

CONTEXT: Prostate-specific antigen (PSA) evaluation leads to the early detection of both prostate cancer and recurrences following primary treatment. Prostate-specific antigen outcome information on patients 5 or more years following treatment is limited and available mainly as single-institution reports. OBJECTIVES: To assess the likelihood and durability of tumor control using PSA evaluation 5 or more years after radical external beam radiation therapy and to identify pretreatment prognostic factors in men with early prostate cancer treated since 1988, the PSA era. DESIGN AND SETTING: Retrospective, nonrandomized, multi-institutional pooled analysis of patients treated with external beam radiation therapy alone between 1988 and 1995 at 6 US medical centers. Follow-up lasted up to a maximum of 9 years. Outcome data were analyzed using Cox regression and recursive partitioning techniques. PATIENTS: A total of 1765 men with stage T1b, T1c, and T2 tumors treated between 1988 and 1995 with external beam radiation. The majority (58%) of patients were older than 70 years and 24.2% had initial PSA values of 20 ng/mL or higher. A minimum of 2 years of subsequent follow-up was required for participation. MAIN OUTCOME MEASURE: Actuarial estimates of freedom from biochemical failure. RESULTS: The 5-year estimates of overall survival, disease-specific survival, and the freedom from biochemical failure are 85.0% (95% confidence interval [CI], 82.5%-87.6%), 95.1% (95% CI, 94.0%-96.2%), and 65.8% (95% CI, 62.8%-68.0%), respectively. The PSA failure-free rates 5 and 7 years after treatment for patients presenting with a PSA of less than 10 ng/mL were 77.8% (95% CI, 74.5%-81.3%), and 72.9% (95% CI, 67.9%-78.2%). Recursive partitioning analysis of initial PSA level, palpation stage, and the Gleason score groupings yielded 4 separate prognostic groups: group 1, included patients with a PSA level of less than 9.2 ng/mL; group 2, PSA level of at least 9.2 but less than 19.7 ng/mL; group 3, PSA level at least 19.7 ng/mL and a Gleason score of 2 to 6; and group 4, PSA level of at least 19.7 ng/mL and a Gleason score of 7 to 10. The estimated rates of survival free of biochemical failure at 5 years are 81 % for group 1, 69% for group 2, 47% for group 3, and 29% for group 4. Of the 302 patients followed up beyond 5 years who were free of biochemical disease, 5.0% relapsed from the fifth to the eighth year. CONCLUSIONS: Estimated PSA control rates in this pooled analysis are similar to those of single institutions. These rates indicate the probability of success for subsets of patients with tumors of several prognostic category groupings. These results represent a multi-institutional benchmark for evidence-based counseling of prostate cancer patients about radiation treatment.