Nomogram to predict rectal toxicity following prostate cancer radiotherapy

Abstract

Background: To identify predictors of acute and late rectal toxicity following prostate cancer radiotherapy (RT), while integrating the potential impact of RT technique, dose escalation, and moderate hypofractionation, thus enabling us to generate a nomogram for individual prediction.

Methods: In total, 972 patients underwent RT for localized prostate cancer, to a total dose of 70 Gy or 80 Gy, using two different fractionations (2 Gy or 2.5 Gy/day), by means of several RT techniques (3D conformal RT [3DCRT], intensity-modulated RT [IMRT], or image-guided RT [IGRT]). Multivariate analyses were performed to identify predictors of acute and late rectal toxicity. A nomogram was generated based on the logistic regression model used to predict the 3-year rectal toxicity risk, with its accuracy assessed by dividing the cohort into training and validation subgroups.

Results: Mean follow-up for the entire cohort was 62 months, ranging from 6 to 235. The rate of acute Grade ≥2 rectal toxicity was 22.2%, decreasing when combining IMRT and IGRT, compared to 3DCRT (RR = 0.4, 95%CI: 0.3-0.6, p<0.01). The 5-year Grade ≥2 risks for rectal bleeding, urgency/tenesmus, diarrhea, and fecal incontinence were 9.9%, 4.5%, 2.8%, and 0.4%, respectively. The 3-year Grade ≥2 risk for overall rectal toxicity increased with total dose (p<0.01, RR = 1.1, 95%CI: 1.0-1.1) and dose per fraction (2Gy vs. 2.5Gy) (p = 0.03, RR = 3.3, 95%CI: 1.1-10.0), and decreased when combining IMRT and IGRT (RR = 0.50, 95% CI: 0.3-0.8, p<0.01). Based on these three parameters, a nomogram was generated.

Conclusions: Dose escalation and moderate hypofractionation increase late rectal toxicity. IMRT combined with IGRT markedly decreases acute and late rectal toxicity. Performing combined IMRT and IGRT can thus be envisaged for dose escalation and moderate hypofractionation. Our nomogram predicts the 3-year rectal toxicity risk by integrating total dose, fraction dose, and RT technique.

Fig 1. Risk of late rectal toxicity (Grade ≥2), overall and by symptoms (SOMA-LENT classification).

Fig 2. Impact of dose escalation on the Grade ≥2 overall rectal toxicity risk.

The patients (n = 491) received either a total dose of 70Gy (n = 277) or 78-80Gy (n = 220), using the same 3D conformal RT technique.

Fig 3. Impact of hypofractionation on the Grade ≥2 overall rectal toxicity (Fig 3A) and rectal bleeding risks (Fig 3B).

The patients (n = 555) received a total dose of 70 Gy with the same 3D conformal RT technique, at either 2 Gy/fr (n = 272) or 2.5 Gy/fr (n = 283).

Fig 4. Impact of the radiation technique on the overall rectal toxicity (Grade ≥2) risk when delivering high doses to the prostate.

The patients (n = 401) received a total dose of 78–80 Gy, by means of either 3DCRT (n = 220) or IMRT alone (n = 63), or by combining IMRT and IGRT (n = 128).

Fig 5. Nomogram and calibration plot (validation cohort) for the 3-year Grade ≥2 overall late rectal toxicity risk.

3DCRT: 3D conformal radiotherapy, IGRT: image-guided radiotherapy, IMRT: intensity-modulated radiotherapy. To use the nomogram, align a straight edge so that it intersects with each predictor line (RT technique, total dose, or dose per fraction), then read the corresponding "Points" on the first line for each predictor. Add the points of the three predictors in order to calculate the total points. Align your straight edge to the "Total points" line and read the toxicity "Risk" on the last line. For example, a patient treated with IMRT and IGRT (0 points) to a total dose of 80 Gy (65 points) at 2 Gy (0 points) per fraction has a risk of late rectal toxicity of 7% (65 points). Calibration plot to assess the nomogram performance by a nonparametric fit of the predicted probability versus actual observed probability in the validation cohort. The corresponding C-index is 60%.