Identification of Site-specific Recurrence Following Primary Radiation Therapy for Prostate Cancer Using C-11 Choline Positron Emission Tomography/Computed Tomography: A Nomogram for Predicting Extrapelvic Disease

Abstract

Background: Management of recurrent prostate cancer (CaP) after radiotherapy (RT) is dependent on accurate localization of the site of recurrent disease.

Objective: To describe the anatomic patterns and clinical features associated with CaP recurrence following RT identified on advanced imaging.

Design, setting, and participants: Retrospective review of 184 patients with a rising prostate-specific antigen (PSA) after RT for CaP.

Intervention: C-11 choline positron emission tomography/computed tomography (CholPET).

Outcome measurements and statistical analysis: Recurrence patterns were classified as pelvic soft tissue only (as a surrogate for potentially salvageable disease) versus any extrapelvic disease, and clinical features were compared between patterns. Multivariable logistic regression was used to generate a predictive nomogram for extrapelvic recurrence. Discrimination was assessed with a c-index.

Results and limitations: Recurrence site was identified in 161 (87%) patients, with 95 (59%) sites histologically confirmed. Factors associated with the detection of recurrence included the difference between PSA nadir and PSA at CholPET (odds ratio: 1.30, p<0.01) and National Comprehensive Cancer Network high-risk classification (odds ratio: 10.83, p=0.03). One hundred (54.3%) patients recurred in the pelvic soft tissue only, while 61 (33%) had extrapelvic recurrence. Of 21 patients who underwent CholPET prior to meeting the Phoenix criteria of biochemical failure, 15 (71%) had recurrence identified on CholPET with 11 localized to the pelvis. On multivariable analysis, the difference between PSA nadir and PSA at CholPET, time from RT, and National Comprehensive Cancer Network risk group were predictive of recurrence outside of the pelvis, and a nomogram was generated with a c-index of 0.79.

Conclusions: CholPET identified the site of recurrence in 87% of patients with a rising PSA after RT; most commonly within the pelvis in potentially salvageable locations. A predictive nomogram was generated, and pending external validation, this may aid in assessing the risk of disease beyond the pelvis. These findings underscore the importance of advanced imaging when considering management strategies for patients with a rising PSA following primary RT.

Patient summary: We identified anatomic patterns of recurrence in patients with a rising prostate-specific antigen after radiotherapy using C-11 choline positron emission tomography/computed tomography. Most recurrences were localized to the pelvis and we were able to generate a tool to aid in disease localization prior to evaluation with advanced imaging.

Keywords: Nomogram; PET/CT; Prostate Cancer; Radiation Therapy; Recurrence.

Fig. 1

Nomogram analysis (A) calculating the probability of identifying extrapelvic and/or osseous disease on C-11 choline positron emission tomography/computed tomography at time of evaluation with a rising prostate-specific antigen (PSA) after primary radiotherapy (RT). Points are assigned by drawing a vertical line from each variable (ΔPSA, time from RT, and National Comprehensive Cancer Network [NCCN] risk group) to the “Points” line and adding the cumulative points. A line is then drawn down from the “Total Points” line at the corresponding point value. Where this line intersects with the “Probability of Extrapelvic Recurrence” line corresponds to the estimated probability of extrapelvic disease. (B) Decision-curve analysis comparing the net-benefit of using the nomogram (black dashed line) depicted above to the strategy of using PSA as a continuous predictor (red dashed line), a PSA cut-off of 3 ng/ml (green dashed line), or a PSA cut-off of 10 ng/ml (blue dashed line)

Fig. 1

Nomogram analysis (A) calculating the probability of identifying extrapelvic and/or osseous disease on C-11 choline positron emission tomography/computed tomography at time of evaluation with a rising prostate-specific antigen (PSA) after primary radiotherapy (RT). Points are assigned by drawing a vertical line from each variable (ΔPSA, time from RT, and National Comprehensive Cancer Network [NCCN] risk group) to the “Points” line and adding the cumulative points. A line is then drawn down from the “Total Points” line at the corresponding point value. Where this line intersects with the “Probability of Extrapelvic Recurrence” line corresponds to the estimated probability of extrapelvic disease. (B) Decision-curve analysis comparing the net-benefit of using the nomogram (black dashed line) depicted above to the strategy of using PSA as a continuous predictor (red dashed line), a PSA cut-off of 3 ng/ml (green dashed line), or a PSA cut-off of 10 ng/ml (blue dashed line)