Patrick A. Kupelian

Pretreatment Nomogram for Predicting the Outcome of Three-Dimensional Conformal Radiotherapy in Prostate Cancer

PURPOSEnSeveral studies have defined risk groups for predicting the outcome after external-beam radiotherapy of localized prostate cancer. However, most models formed patient risk groups, and none of these models considers radiation dose as a predictor variable. The purpose of this study was to develop a nomogram to improve the accuracy of predicting outcome after three-dimensional conformal radiotherapy.nnnMATERIALS AND METHODSnThis study was a retrospective, nonrandomized analysis of patients treated at the Memorial Sloan-Kettering Cancer Center between 1988 and 1998. Clinical parameters of the 1,042 patients included stage, biopsy Gleason score, pretreatment serum prostate-specific antigen (PSA) level, whether neoadjuvant androgen deprivation therapy was administered, and the radiation dose delivered. Biochemical (PSA) treatment failure was scored when three consecutive rises of serum PSA occurred. A nomogram, which predicts the probability of remaining free from biochemical recurrence for 5 years, was validated internally on this data set using a bootstrapping method and externally using a cohort of patients treated at the Cleveland Clinic, Cleveland, OH.nnnRESULTSnWhen predicting outcomes for patients in the validation data set from the Cleveland Clinic, the nomogram had a Somers D rank correlation between predicted and observed failure times of 0.52. Predictions from this nomogram were more accurate (P<.0001) than the best of seven published risk stratification systems, which achieved a Somers D coefficient of 0.47.nnnCONCLUSIONnThe development process illustrated here produced a nomogram that seems to predict more accurately than other available systems and may be useful for treatment selection by both physicians and patients.

International Validation of a Preoperative Nomogram for Prostate Cancer Recurrence After Radical Prostatectomy

PURPOSEnWe evaluated the predictive accuracy of a recently published preoperative nomogram for prostate cancer that predicts 5-year freedom from recurrence. We applied this nomogram to patients from seven different institutions spanning three continents.nnnMETHODSnClinical data of 6,754 patients were supplied for validation, and 6,232 complete records were used. Nomogram-predicted probabilities of 60-month freedom from recurrence were compared with actual follow-up in two ways. First, areas under the receiver operating characteristic curves (AUCs) were determined for the entire data set according to several variables, including the institution where treatment was delivered. Second, nomogram classification-based risk quadrants were compared with actual Kaplan-Meier plots.nnnRESULTSnThe AUC for all institutions combined was 0.75, with individual institution AUCs ranging from 0.67 to 0.83. Nomogram predictions for each risk quadrant were similar to actual freedom from recurrence rates: predicted probabilities of 87% (low-risk group), 64% (intermediate-low-risk group), 39% (intermediate-high-risk group), and 14% (high-risk group) corresponded to actual rates of 86%, 64%, 42%, and 17%, respectively. The use of neoadjuvant therapy, variation in the prostate-specific antigen recurrence definitions between institutions, and minor differences in the way the Gleason grade was reported did not substantially affect the predictive accuracy of the nomogram.nnnCONCLUSIONnThe nomogram is accurate when applied at international treatment institutions with similar patient selection and management strategies. Despite the potential for heterogeneity in patient selection and management, most predictions demonstrated high concordance with actual observations. Our results demonstrate that accurate predictions may be expected across different patient populations.

Pretreatment Nomogram That Predicts 5-Year Probability of Metastasis Following Three-Dimensional Conformal Radiation Therapy for Localized Prostate Cancer

PURPOSEnThere are several nomograms for the patient considering radiation therapy for clinically localized prostate cancer. Because of the questionable clinical implications of prostate-specific antigen (PSA) recurrence, its use as an end point has been criticized in several of these nomograms. The goal of this study was to create and to externally validate a nomogram for predicting the probability that a patient will develop metastasis within 5 years after three-dimensional conformal radiation therapy (CRT).nnnPATIENTS AND METHODSnWe conducted a retrospective, nonrandomized analysis of 1,677 patients treated with three-dimensional CRT at Memorial Sloan-Kettering Cancer Center (MSKCC) from 1988 to 2000. Clinical parameters examined were pretreatment PSA level, clinical stage, and biopsy Gleason sum. Patients were followed until their deaths, and the time at which they developed metastasis was noted. A nomogram for predicting the 5-year probability of developing metastasis was constructed from the MSKCC cohort and validated using the Cleveland Clinic series of 1,626 patients.nnnRESULTSnAfter three-dimensional CRT, 159 patients developed metastasis. At 5 years, 11% of patients experienced metastasis by cumulative incidence analysis (95% CI, 9% to 13%). A nomogram constructed from the data gathered from these men showed an excellent ability to discriminate among patients in an external validation data set, as shown by a concordance index of 0.81.nnnCONCLUSIONnA nomogram with reasonable accuracy and discrimination has been constructed and validated using an external data set to predict the probability that a patient will experience metastasis within 5 years after three-dimensional CRT.

Biochemical and clinical significance of the posttreatment prostate-specific antigen bounce for prostate cancer patients treated with external beam radiation therapy alone Presented at the 46th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, Atlanta, GA, October 3–7, 2004.

The posttreatment prostate‐specific antigen (PSA) bounce phenomenon has been recognized in at least 20% of all patients treated with radiation. The purpose of the current report was to determine if there was a difference in biochemical and clinical control between the bounce and nonbounce (NB) patients using pooled data on 4839 patients with T1‐2 prostate cancer treated with external beam radiation therapy (RT) alone at 9 institutions between 1986 and 1995.

Counseling Patients With Localized Prostate Cancer

The treatment of localized prostate cancer remains controversial because of the lack of conclusive well-controlled or randomized studies comparing outcomes of radiotherapy (RT) and radical prostatectomy (RP). A randomized trial published in 1982 showing an advantage to RP was never widely accepted because of randomization artifacts and worse than previously reported RT results (1,2). The Southwest Oncology Group closed a randomized study comparing these two modalities in the mid-1980s owing to poor accrual. In 1993, Stamey et al. (3) reported a 20% 5-yr biochemical cure rate with RT and suggested that radiation accelerates prostate cancer growth. Subsequently, large RT series were published with outcome results stratified by biopsy grade, T stage, and serum PSA, demonstrating similar short-term outcomes for RT and RP (4–6). A close examination of the patients treated by RT in the series of Stamey et al. (3) suggests that the observation of a 20% “cure” rate with RT can largely be explained by patient selection factors—all patients had high-volume cancers diagnosed by palpable lesions, 35% had clinical stage C disease, 50% had Gleason sum ≥7, and 15% had positive lymph nodes (7). Furthermore, Liebman et al. (8) have subsequently demonstrated that prostate-specific antigen (PSA) velocity is similar in those who fail radiation or surgery. None of these studies clearly answers the question of which is the best local therapy for localized prostate cancer. The unsettled nature of this issue is further complicated by the marked polarization of radiation oncologists and urologists in their counseling of patients with newly diagnosed localized disease, with surgeons recommending surgery and radiation therapists recommending radiation in virtually all circumstances (9).