External Beam Treatment Research Articles

Facilitation of radiotherapeutic error by computerized record and verify systems

Purpose To examine the impact of computerized record and verify (R&V) systems on types of radiotherapeutic error. Methods and materials Radiation therapy treatment errors reported by therapists at the University of Utah between July 1, 1999 and June 30, 2000 were retrospectively reviewed. Results During a 1-year period in which 22,542 external beam radiation therapy treatments were administered, 38 treatment errors (representing 0.17% of external beam treatments administered during this period) were identified and reviewed. Nine cases (0.04% of treatments) representing four types of record and verify (R&V)-related errors were identified, in which the department’s R&V system played a contributory role in the treatment error. Conclusions The common denominator among these R&V-related errors was excessive reliance upon the computer system by therapists. R&V systems eliminate some, but not all, pathways of radiotherapeutic error. Although R&V systems have assumed a crucial role in the precise and reproducible delivery of increasingly complex radiation therapy treatments, their inability to eradicate all radiotherapeutic errors coupled with their parallel ability to facilitate certain mistakes mandates vigilance on the part of the radiation therapy team. Radiation therapy treatment procedures must preserve careful oversight of R&V functions to minimize prospects for treatment error.

859 Poster Re-irradiation with external beam treatment of non-small cell lung carcinoma (NSCLC)

859 Poster Re-irradiation with external beam treatment of non-small cell lung carcinoma (NSCLC)

Biochemical Disease-Free Survival in Men Younger Than 60 Years With Prostate Cancer Treated With External Beam Radiation

We determined the biochemical failure rate in patients 60 years and younger, and older than 60 years old who were treated with external beam radiation for localized prostate cancer or locally advanced prostate cancer. We also evaluated prognostic factors in the 2 age groups. We reviewed the medical records of 964 patients who received full dose radiotherapy as the only treatment for prostate cancer. Followup prostate specific antigen was measured 3 to 6 months after the completion of radiotherapy and every 3 to 6 months thereafter. Biochemical failure was defined using the criteria established by the American Society for Therapeutic Radiology and Oncology Consensus Panel. Median followup in the whole study group was 48 months. Of the 98 men 60 years or younger 46 (47%) had biochemical failure, whereas 261 (30%) of the 866 older than 60 years old had biochemical failure. The 5 and 7-year biochemical disease-free survival rates were 55% and 47% in the younger men, and 65% and 59% in the older men, respectively. These rates were significantly lower in the younger men (p = 0.017 and 0.027, respectively). Multivariate regression showed that in men 60 years or younger initial prostate specific antigen, Gleason score and lower radiation doses were predictive of biochemical failure. Men with prostate cancer who are 60 years or younger and treated with radiotherapy may be at significant risk for long-term biochemical failure.

Comparison of cosmetic outcome between peroperative implants and implants after external beam treatment in the breast conserving treatment for breast cancer

Comparison of cosmetic outcome between peroperative implants and implants after external beam treatment in the breast conserving treatment for breast cancer

Design of a multiblock phantom for radiotherapy dosimetry applications.

This note describes the design of a multiblock semi-anatomic phantom, which lends itself to a variety of radiotherapy dosimetry applications, in particular, the audit of external beam treatment planning and delivery. The basic building blocks of the phantom were formed from a variety of tissue substitute materials and could be assembled in many ways to model different cross-sections through the body.

Long-term outcome after elective irradiation of the pelvic lymphatics and local dose escalation using high-dose-rate brachytherapy for locally advanced prostate cancer

Purpose: To report the 8-year outcome of local dose escalation using high-dose-rate conformal brachytherapy combined with elective irradiation of the pelvic lymphatics for localized prostate cancer. Methods and Materials: One hundred forty-four consecutively treated men (1986–1992) were recorded prospectively. Twenty-nine (20.14%) patients had T1b–2a tumors, and 115 (79.86%) patients had T2b–3 tumors according to, respectively, American Joint Committee on Cancer/Union Internationale Contre le Cancer 1992. All patients had a negative nodal status, proven by CT or MRI. The mean initial PSA value was 25.61 ng/mL (Initial value for 41.66% of patients was <10 ng/mL, for 21.52% was 10–20 ng/mL, and for 32.63% was >20 ng/mL). The total dose applied by external beam radiotherapy was 50 Gy in the pelvis and 40 Gy in the prostate. The high-dose-rate brachytherapy was delivered in two fractions, which were incorporated into the external beam treatment (after 20-Gy and 40-Gy external beam radiotherapy dose). The dose per fraction was 15 Gy for the PTV1 (peripheral prostate zone) and 9 Gy for the PTV2 (entire prostatic gland). Any patient free of clinical or biochemical evidence of disease was termed bNED. Actuarial rates of outcome were calculated by Kaplan-Meier and compared using the log-rank. Cox regression models were used to establish prognostic factors of the various measures of outcome. Results: The median follow-up was 8 years (range 60–171 months). The overall survival rate was 71.5%, and the disease-free survival rate was 82.6%. The bNED survival rate was 72.9%. Freedom from local recurrence for T3 stage was 91.3%, whereas for G3 lesions it was 88.23%. Freedom from distant recurrence for T3 stage was 82.6% and for G3 lesions 70.59%. Univariate survival analyses revealed that low stage (T1–2), low grade (G1–2), no hormonal therapy, initial PSA value less than 40 ng/mL, and PSA normalization <1.0 ng/mL after irradiation were associated with long survival. In multivariate analyses, initial PSA value, PSA kinetics after radiation therapy, and no adjuvant hormonal treatment were independent prognostic factors. Grade 3 late radiation toxicity (according to RTOG/EORTC scoring scheme) was 2.3% for the genitourinary system in terms of cystitis and 4.10% for the gastrointestinal system in terms of proctitis. Grades 4 and 5 genitourinary/gastrointestinal morbidity was not observed. A history of transurethral resection of the prostate with a median interval of less than 6 months from radiotherapy was associated with a high risk of genitourinary toxicity. Conclusion: The 8-year results confirm the feasibility and effectiveness of combined elective irradiation of the pelvic lymphatics and local dose escalation using high-dose-rate brachytherapy for cure of localized and especially high-risk prostate cancer.

The influence of interpatient and intrapatient rectum variation on external beam treatment of prostate cancer

Purpose: The rectal dose/volume relationship and inherent variations thereof are fundamental parameters to guide dose escalation in prostate cancer treatment. This study evaluates the effect of rectal dose/volume variation on the risk of rectal complication for different planning target volume (PTV) constructions.Methods and Materials: Thirty prostate patients with multiple daily CT scans obtained during the treatment course were included in this retrospective study. The dose distribution was calculated based on the pretreatment CT image alone. Treatment plans were generated by applying the four-field-box beam arrangement to each of three different PTVs: PTVs with 0.5-cm and 1.0-cm uniform margins, and a patient-specific PTV constructed using treatment imaging feedback. For each of the 30 patients, the rectal wall as manifested on each of multiple CT images was delineated after image bony registration to the pretreatment CT image, and applied to the corresponding treatment plan to obtain the rectal wall dose-volume histogram (DVH). Interpatient and intrapatient rectal dose/volume variations were quantified accordingly. The corresponding uncertainty and sensitivity of the risk of rectal complication to the variations were evaluated for each of the three PTVs. Finally, the efficacy of using multiple CT images to reduce uncertainty in planning evaluation was examined.Results: Sensitivity of the risk of rectal complication to rectal dose/volume variation strongly depends on the clinical target volume (CTV)-to-PTV margin or prescription dose, or both. Compared to the conventional two-dimensional (2D) prostate cancer treatment, the sensitivity for a conformal treatment can be 3 times higher or more. Due to the interpatient rectal dose/volume variation, the individual normal tissue complication probability (NTCP) was distributed from 10% to 37% when a common prescription dose was applied for all patients. The intrapatient rectal dose/volume variation introduces at least ± 25% uncertainty in the NTCP calculation for at least 10% or 25% of the patients treated with the PTV of 1.0- or 0.5-cm margin, respectively. These uncertainties were larger for the smaller PTV, with the standard deviation up to 20%. By applying multiple CT image feedback, the NTCP uncertainty could be reduced by a factor of 2.Conclusions: Shape and position variation of rectum has less influence on treatment planning in the conventional 2D treatment of prostate cancer. However, this influence is quickly growing with high treatment dose or small CTV-to-PTV margins. To reduce the variation and uncertainties in the treatment planning evaluation associated with the inter- and intrapatient rectal dose/volume variation, the iso-NTCP model and treatment image feedback technique can be applied in dose escalation trials of prostate cancer treatment.

3Integration of CT-based intracavitary brachytherapy and external beam treatment planning: An analysis of the combined dose distribution

3Integration of CT-based intracavitary brachytherapy and external beam treatment planning: An analysis of the combined dose distribution

High dose rate brachytherapy boost treatment in radical radiotherapy for prostate cancer

The natural history of prostate cancer is for early invasion of the prostatic capsule and seminal vesicles. This will be present in the majority of patients presenting with a prostate specific antigen (PSA) >10 or Gleason score >7. In these patients a combination of external beam treatment to provide a regional dose of radiation followed by a high dose rate afterloading brachytherapy boost to enable conformal dose escalation within the prostate gland presents an attractive option in local treatment. Accurate placement of catheters is now possible using transrectal ultrasound to provide high quality implants. A number of centres have now developed this technique as a routine clinical tool. There remains variation in the optimal dose fractionation with a range of BED 10 values from 100 to 77 and BED 3 values from 246.6 to 122.5. This does not, however, take into account geometric variations in dose distribution exploiting the physical advantage of BT in achieving a rapid dose fall off close to critical structures such as the rectum. Early results show PSA response levels of around 90% with grade III toxicity in 5–9% of patients. Critical evaluation of this technique in prospective, randomized trials is required.

Estimating the dose variation in a volume of interest with explicit consideration of patient geometric variation.

A method to measure the effects of internal organ motion and deformation and patient setup error on cumulative dose variation in a volume of interest is proposed. The method uses multiple CT scans and electronic portal images of a single patient to numerically simulate dose-volume effects over the entire course of the patient's external beam treatment. The results are expressed in the form of a novel dose-volume histogram, called an expected dose-volume histogram (EDVH).

Preclinical studies with the photon radiosurgery system (PRS)

Purpose: Determine the radiobiological effectiveness (RBE) for low-energy X-rays (average energy of 23 KeV) produced by the Photon Radiosurgery System (PRS). Methods and Materials: RBE values were assessed by comparison with survival data obtained for cells irradiated with either low-energy X-rays from a GE Maxitron 100 machine or high-energy photons from a clinically used Varian 6 MV LINAC. The output of the GE and PRS sources was determined using Baldwin-Farmer and Markus thin window ionization chambers calibrated with 50 kVp X-rays and cross-checked against figures supplied by Photoelectron Corporation. The dose-rate for the PRS was 1.2 Gy/min at a distance of 35 mm with a field flatness of ±2%. Results: The RBE for the PRS low-energy X-ray source (at 1-mm depth) was greater than either the GE or Varian machines and varied with cell survival. For Chinese hamster ovary (CHO) cells, the PRS was 1.25 and 3.3 times more effective than 90 kVp X-rays and 6 MeV photons at 0.5% cell survival, respectively; by comparison, the PRS was 1.2 and 1.9 times more effective at 0.05% cell survival, respectively. Similar RBE values of 1.4 and 1.2 were obtained for human U373 and T98 glioblastoma cells grown in vitro irradiated with the PRS or GE sources, respectively. Other studies showed that the RBE for the PRS low-energy X-ray source increased with depth. The RBEs for the PRS source at 1-mm and 4-mm depth were 1.2 and 2.5 (0.5% survival) and 1.2 and 1.9 (0.05% survival). Conclusions: The biological and physical properties of the PRS low-energy X-rays offer, under the right conditions, a significant advantage for patient treatment over conventional external beam, stereotactic, or brachytherapy treatment.

A comparison of two methods for estimating the technical costs of external beam radiation therapy

Purpose: To accurately assess the cost-effectiveness of treatment with external beam radiation, it is necessary to have accurate estimates of its cost. One of the most common methods for estimating technical costs has been to convert Medicare charges into costs using Medicare Cost-to-Charge Ratios (CCR). More recently, health care organizations have begun to invest in sophisticated cost-accounting systems (CAS) that are capable of providing procedure-specific cost estimates. The purpose of this study was to examine whether these competing approaches result in similar cost estimates for four typical courses of external beam radiation therapy (EBRT). Methods and Materials: Technical costs were estimated for the following treatment courses: 1) a palliative “simple” course of 10 fractions using a single field without blocks; 2) a palliative “complex” course of 10 fractions using two opposed fields with custom blocks; 3) a curative course of 30 fractions for breast cancer using tangent fields followed by an electron beam boost; and 4) a curative course of 35 fractions for prostate cancer using CT-planning and a 4-field technique. Costs were estimated using the CCR approach by multiplying the number of units of each procedure billed by its Medicare charge and CCR and then summing these costs. Procedure-specific cost estimates were obtained from a cost-accounting system, and overall costs were then estimated for the CAS approach by multiplying the number of units billed by the appropriate unit cost estimate and then summing these costs. All costs were estimated using data from 1997. The analysis was also repeated using data from another academic institution to estimate their costs using the CCR and CAS methods, as well as the appropriate relative value units (RVUs) and conversion factor from the 1997 Medicare Fee Schedule to estimate Medicare reimbursement for the four treatment courses. Results: The estimated technical costs for the CCR vs. CAS approaches for the four treatment courses were as follows: palliative “simple” $1,285 vs. $1,195; palliative “complex” $2,345 vs. $1,769; curative breast $6,757 vs. $4,850; and curative prostate $9,453 vs. $7,498. Accordingly, the CCR estimates were 8%, 33%, 39%, and 26% higher than the CAS cost estimates, respectively. The primary cause of the difference between the estimates was the daily cost of delivering a “complex” treatment. In fact, if corrected the difference between the estimates fell to 0%, 1%, 4%, and 0%, respectively. Similar results were observed for both methods when the analysis was repeated using data from another academic institution. Medicare reimbursement was also slightly lower than, but remarkably close to, the costs estimated by the CAS approach. Conclusions: For “complex” treatment courses, which represent the vast majority of external beam treatments, technical costs estimated using the CCR approach appear to be significantly higher than those estimated using procedure-specific cost estimates. Because cost-effectiveness analyses of radiation therapy tend to be sensitive to the cost of treatment, the use of higher costs will result in radiation therapy appearing less cost-effective.

Normal tissue dosimetric comparison between hdr prostate implant boost and conformal external beam radiotherapy boost: potential for dose escalation

Purpose: To compare the dose and volume of bladder and rectum treated using high-dose-rate (HDR) prostate implant boost versus conformal external beam radiotherapy boost, and to use the dose–volume information to perform a critical volume tolerance (CVT) analysis and then estimate the potential for further dose escalation using HDR brachytherapy boost. Methods and Materials: Using CT scan data collected before and after patients underwent HDR prostate implant, a 7-field conformal prostate-only external beam treatment plan and HDR brachytherapy treatment plan were constructed for each patient. Doses to the normal structures were calculated. Dose–volume histograms (DVH) were plotted for comparison of the two techniques. Wilcoxon signed rank test was performed at four dose levels to compare the dose to normal structures between the two treatment techniques. The acute and late effects of HDR brachytherapy were calculated based on the linear-quadratic (LQ) model. CVT analyses were performed to calculate the potential dose gain (PDG) using HDR brachytherapy boost. Results: The volume of bladder and rectum receiving high dose was significantly less from implant boost. On the average, 0.19 cc of the bladder received 100% of the brachytherapy prescription dose, compared with 5.1 cc of the bladder receiving 100% of the prescription dose in the 7-field conformal external beam radiotherapy boost. Similarly, 0.25 cc of the rectum received 100% of the dose with the implant boost, as compared to 2.9 cc in the conformal external beam treatment. The implant also delivered higher doses inside the prostate volume. On average, 47% of the prostate received ≥150% of the prescription dose. The CVT analysis revealed a range of PDG using the HDR brachytherapy boost which depended on the following variables: critical volume (CV), critical volume tolerance dose (CVTD), number of HDR fractions (N), and the dose of external beam radiotherapy (XRT) delivered with brachytherapy boost. The PDG varied from −3.45% to 10.53% for tumor with an alpha–beta ratio of 10 and 7.14% to 64.6% for tumor with an alpha–beta ratio of 1.5 based on the parameters used for calculation in this study. Conclusions: HDR brachytherapy can provide better sparing of rectum and bladder while delivering a higher dose to the prostate. Even with the increased late effects of high dose per fraction, there is still a potential for dose escalation beyond external radiotherapy limits using HDR brachytherapy.

Limitations of reduced-field irradiated volume and technique in conventional radiation therapy of prostate cancer:Implications for conformal 3-D treatment

In order to define technical limitations of conventional external beam irradiation for clinically localized prostate cancer, we evaluated the impact of several reduced-field treatment factors, such as reduced-field (RF) irradiated volume, RF technique, photon energy of treatment, and dose on survival endpoints and local control in a retrospective series. Several survival endpoints, such as disease-specific survival, freedom from relapse survival, biochemical no-evidence of disease (bNED) survival, and local control were associated with several treatment variables using univariate and multivariate analyses in 329 patients. Reduced-field technique appeared to predict survival outcome, with patients treated by bilateral 120 degrees arcs faring less well than those treated by full 360 degrees rotational fields. The irradiated volume of the reduced-field was also significantly associated with survival outcome, with patients treated with smaller volumes faring less well. Local failure rates also appeared increased, although not statistically, in patients treated with smaller RF sizes. In an attempt to explain these detected deficiencies, dose-volume histograms for prostate coverage were created for a small sample of patients. The deficiencies related to small reduced-field volume appeared to be largely attributable to poor dosimetric coverage of the prostate. These results underscore the limitations of conventional external beam treatment for prostate carcinoma when conventional techniques are employed, particularly if small reduced fields are used, and further supports the development of improved treatment techniques, such as conformal irradiation, as alternatives.

Conformal radiotherapy for prostate cancer

This review presents the contribution conformal treatment has made to the external beam treatment of prostate cancer drawing on 10 years of experience with three-dimensional conformal radiation treatment in 1500 patients with prostate cancer at our institution. Major contributions from other institutions and the Radiation Therapy Oncology Group (RTOG) clinical trials group are also noted. Patient immobilization, computed tomography (CT) scan identification of the target in three dimensions and beams-eye-view conformal treatment portals are critical to the process. Higher doses of radiation are associated with a marked increase in cure rates as the dose-response curve is extremely steep. The advantage given by the high dose depending on prognostic group ranges from 14% to 35% in 5-year cures. Conformal techniques protect normal tissues so that late complications are rare and in fact fewer than those observed with standard radiation technique at standard radiation doses. Educational efforts are underway in the USA to assist practising radiation oncologists to deliver the required radiation doses of 75-80 Gy safely. Conformal therapy cures more prostate cancers causing fewer complications than standard treatment technique and standard dose. It must therefore be disseminated into the practice of radiation oncology worldwide.

Prostate preservation by combined external beam and HDR brachytherapy in nodal negative prostate cancer.

The combined external beam- and high-dose rate brachytherapy (HDR-BT) of localized prostate cancer was introduced at Kiel University in 1986. The aim of this intermediate analysis was to judge the Kiel method of localized prostate cancer radiation treatment after ten years experience. In the past ten years 174 patients with histological proven localized prostate cancer were subjected to combined tele-/HDR-brachytherapy. Local staging in all of the cases by transrectal ultrasound, nodal staging in the majority of the cases by CT or MRI. Average age of the patients was 68.2 years (44-84). According to AJCC/UICC staging T1B, T2, T3 was found in 2, 113 and 59 cases, respectively. Highly differentiated tumors (G1) were found in 27, moderately differentiated (G2) in 87, poorly differentiated (G3) in 60 cases. The mean follow-up was 47.1 months with the median of 51.7 months. Total prescribed dose 50 Gy on the small pelvis and 70 Gy on the prostate capsule due to the integration of two, 15 Gy each, HDR-brachytherapy fractions in 6 weeks. Ten patients died of prostate cancer and 18 of intercurrent diseases resulting in a 5 years overall survival rate of 83% and tumor specific survival rate of 94%. Twenty-one patients showed a clinical progression, of these 14 systemic, 5 local and 2 both systemic and local. Additional 16 patients had PSA elevation only. The 5-years biochemical and/or clinical progression-free survival in the cohort was 79% and 73% for the T3 tumors. Side effects were 27 cases of proctitis/colitis and 20 cases of dysuria/cystitis. The integrated HDR-BT combined with external beam radiation treatment is a method with excellent tumor control rates at five years superior to those of external beam treatment alone or external beam combined with iodine-125 implants. This form of radiotherapy would appear to be particularly well-suited to treatment of advanced localized (T3) tumors.

Fractionation and protraction for radiotherapy of prostate carcinoma

Purpose: To investigate whether current fractionation and brachytherapy protraction schemes for the treatment of prostatic cancer with radiation are optimal, or could be improved.Methods and Materials: We analyzed two mature data sets on radiotherapeutic tumor control for prostate cancer, one using EBRT and the other permanent seed implants, to extract the sensitivity to changes in fractionation of prostatic tumors. The standard linear-quadratic model was used for the analysis.Results: Prostatic cancers appear significantly more sensitive to changes in fractionation than most other cancers. The estimated α/β value is 1.5 Gy [0.8, 2.2]. This result is not too surprising as there is a documented relationship between cellular proliferative status and sensitivity to changes in fractionation, and prostatic tumors contain exceptionally low proportions of proliferating cells.Conclusions: High dose rate (HDR) brachytherapy would be a highly appropriate modality for treating prostate cancer. Appropriately designed HDR brachytherapy regimens would be expected to be as efficacious as low dose rate, but with added advantages of logistic convenience and more reliable dose distributions. Similarly, external beam treatments for prostate cancer can be designed using larger doses per fraction; appropriately designed hypofractionation schemes would be expected to maintain current levels of tumor control and late sequelae, but with reduced acute morbidity, together with the logistic and financial advantages of fewer numbers of fractions.

Review of endovascular brachytherapy physics for prevention of restenosis

Intraluminal irradiation of coronary and peripheral arteries has been shown to reduce neointimal hyperplasia following balloon angioplasty, thereby inhibiting restenosis. Several irradiation techniques are being investigated, including temporary intravascular insertion of high activity gamma- or beta-emitting seeds and wires; inflation of dilatation balloon catheter with radioactive liquid or gas; insertion of miniature x-ray tubes via coronary catheters; permanent implantation of radioactive stents; and postangioplasty fractionated external beam irradiation. Unlike conventional brachytherapy, intravascular treatment of restenosis requires accurate knowledge of dose at distances of 0.5–5 mm from the radioactive source. This requirement presents special problems with regard to source calibration and dose specification, because dose gradients at such close distances from a radioactive source are extremely large. This makes it virtually impossible to define the characteristics of an ideal radiation source without some knowledge of the location and radiosensitivity of the target tissues, plus the radiotolerance of normal tissues. Hence, the current debate over whether beta or gamma sources are to be preferred. Imprecise knowledge of dose–volume effects for coronary arteries, plus uncertainties in the biological time sequencing of restenosis fuel a second debate on whether external beam treatments may be efficacious, and whether or not permanent radioactive stents may prove superior to high dose, single fraction brachytherapy. We review here the dosimetric properties of the various irradiation techniques and isotopes that have been proposed, including aspects of radiation safety, dose homogeneity, and practical aspects of source delivery.

Brachytherapy for the Next Century: Use of Image-Based Treatment Planning

Three-dimensional treatment planning systems used extensively for external-beam treatments have recently been applied for use in brachytherapy. Localization of structures in 3D from imaging studies integrated into computerized systems for planning of implants and evaluation allows 3D dose distributions to be indexed to the patient's anatomy. Correlation of target volume and dose distribution permits planning of conformal dose distributions, which maximizes the dose to the target volume while avoiding dose to normal tissue. Imaging during the implantation process can improve the delivery of the dose distribution planned prior to implantation, which may translate into improved outcome. Postimplant imaging scans can be compared to preimplant planning, providing feedback on the error in source placement and ultimately improving implantation. Application of image-based planning and delivery for ultrasound-guided transperineal prostate implantation is widespread. The first part of this report will discuss in detail a major research effort at our institution to understand and improve the prostate implant process. In the last half of our report, we will describe 3D treatment planning for gynecological implants. Problems with traditional implant planning and delivery procedures (perhaps still used today) and how image-based treatment planning and delivery can improve the implant process will be presented.

Relationship of ultrasound staging and bilateral biopsy positivity to outcome in stage T1c prostate cancer treated with radiotherapy

Objectives. The strict definition of Stage T1c prostate cancer is that the tumor is not palpable on digital rectal examination (DRE) or seen on imaging studies such as ultrasound. The inclusion of ultrasound imaging was brought about without an understanding of the relationship between ultrasound upstaging and prognosis. We have also noticed that in clinical practice, treatment decisions are made on the basis of the finding of bilateral versus unilateral biopsy positivity. The objectives in this study were to determine the prognostic significance of upstaging by transrectal ultrasound (TRUS) to uT2 or uT3, and unilateral versus bilateral biopsy positivity in patients with Stage T1c cancer as determined by DRE (DRE-Stage T1c patients). Methods. Between 1987 and 1995 there were 643 patients with DRE-Stage T1-T2 prostate cancer treated with external beam radiotherapy; 24 had T1a, 76 had T1b, 183 had T1c, 133 had T2a, 168 had T2b, and 59 had T2c. Of these, 135 DRE-Stage T1c patients underwent ultrasound staging and 122 underwent bilateral prostate biopsies. All had pretreatment prostate-specific antigen values (PSAs) available and no patient received adjuvant androgen ablation. The median pretreatment PSA was 9.1 ng/mL, median radiotherapy dose was 66.0 Gy, and median follow-up was 41 months. Post-treatment failure was defined as disease recurrence and/or two elevations in PSA on consecutive follow-up visits. Results. The 5-year freedom from failure rate for DRE-Stage T1c patients (71%) was not significantly different from that of DRE-Stage T1b (65%) or DRE-Stage T2a (71%) patients. There was a trend ( P = 0.1) toward a worse outcome for DRE-Stage T2b/T2c patients compared with DRE-Stage T1b/T1c/T2a patients. The distribution of DRE-Stage T1c patients by ultrasound staging was 29 with uT1c, 88 with uT2, and 18 with uT3 findings. Twenty percent of patients had bilateral positive biopsy specimens. In univariate and multivariate analyses, the only correlates of patient outcome were pretreatment PSA ( P ≤ 0.002) and isocenter dose ( P = 0.03). TRUS upstaging had no effect on freedom from failure; uT1c patients had about the same risk of relapse or a rising PSA as uT2 or uT3 patients. Patients with bilateral positive prostate biopsy specimens had about the same prognosis as those with unilateral positive biopsy specimens. Conclusions. For patients with DRE-Stage T1c prostate cancer, the data indicate that ultrasound staging and bilateral biopsy positivity are not predictive of outcome for patients treated with external beam radiotherapy and treatment decisions should not be based on these parameters.