Late Genitourinary Research Articles

Estimation of the Incidence of Late Bladder and Rectum Complications After High-Dose (70–78 Gy) Conformal Radiotherapy for Prostate Cancer, Using Dose–Volume Histograms

Purpose: To investigate whether Dose–Volume Histogram (DVH) parameters can be used to identify risk groups for developing late gastrointestinal (GI) and genitourinary (GU) complications after conformal radiotherapy for prostate cancer. Methods and Materials: DVH parameters were analyzed for 130 patients with localized prostate cancer, treated with conformal radiotherapy in a dose-escalating protocol (70–78 Gy, 2 Gy per fraction). The incidence of late (>6 months) GI and GU complications was classified using the RTOG/EORTC and the SOMA/LENT scoring system. In addition, GI complications were divided in nonsevere and severe (requiring one or more laser treatments or blood transfusions) rectal bleeding. The median follow-up time was 24 months. We investigated whether rectal and bladder wall volumes, irradiated to various dose levels, correlated with the observed actuarial incidences of GI and GU complications, using volume as a continuous variable. Subsequently, for each dose level in the DVH, the rectal wall volumes were dichotomized using different volumes as cutoff levels. The impact of the total radiation dose, and the maximum radiation dose in the rectal and bladder wall was analyzed as well. Results: The actuarial incidence at 2 years for GI complications ≥Grade II was 14% (RTOG/EORTC) or 20% (SOMA/LENT); for GU complications ≥Grade III 8% (RTOG/EORTC) or 21% (SOMA/LENT). Neither for GI complications ≥Grade II (RTOG/EORTC or SOMA/LENT), nor for GU complications ≥Grade III (RTOG/EORTC or SOMA/LENT), was a significant correlation found between any of the DVH parameters and the actuarial incidence of complications. For severe rectal bleeding (actuarial incidence at 2 years 3%), four consecutive volume cutoff levels were found, which significantly discriminated between high and low risk. A trend was observed that a total radiation dose ≥ 74 Gy (or a maximum radiation dose in the rectal wall >75 Gy) resulted in a higher incidence of severe rectal bleeding ( p = 0.07). Conclusions: These data show that dose escalation up to 78 Gy, using a conformal technique, is feasible. However, these data have also demonstrated that the incidence of severe late rectal bleeding is increased above certain dose–volume thresholds.

1005 High-dose (70–78 GY) conformal radiotherapy for prostate cancer; the relation between observed late bladder and rectum complications and parameters derived from the dose volume histograms

Purpose: To determine the incidence of late gastrointestinal (GI) and genitourinary (GU) complications after conformal radiotherapy for prostate cancer, and to investigate the relation between these observed incidences and parameters derived from the Dose Volume Histograms (DVHs) of rectum and bladder wall. Patients and Methods: Hundred and thirty patients with T{sub 2-4}G{sub 1-3}N{sub 0}M{sub 0} prostate cancer were treated with conformal radiotherapy with the simultaneous boost technique in a dose-escalating protocol; 78 patients received a total dose of 70 Gy, 11 patients 74 - 76 Gy and 41 patients 78 Gy, each with a dose of 2 Gy per fraction. DVHs of the rectal wall were used to calculate NTCPs according to the model of Kutcher et al. with the estimated parameter values (n = 0.12, m = 0.15, TD{sub 50} = 80 Gy) according to Burman et al. The median follow-up was 17 months (range 6 - 72 months). The crude and actuarial incidence of late (> 6 months) GI and GU complications were determined using the RTOG/EORTC morbidity scoring system (Grade I to IV). Results: Neither for late GI nor for GU complaints, a grade IV complication was observed. GU complaints occurred in 90 patients (69%): 54 patients (42%) only experienced grade I toxicity, 26 patients (20%) had grade II toxicity, and 10 patients (8%) had grade III complications, of which 8 patients (6%) developed a urethral (7 pts) or ureteric stenosis (1 pt). The actuarial incidence of grade III GU complications was 10% at 2 years. Since bladder wall DVHs are unreliable and most grade III complications were not related to the bladder, the grade II and/or III complications were analyzed in terms of the total prescribed dose only, but no correlation could be demonstrated. GI complications occurred in 71 patients (55%): 59 patients (45%) developed a grade I complication, 11 a grade II complication and only 1 patient required laser treatment twice and blood transfusion because of rectal bleeding (grade III). The actuarial incidence of GI complications ({>=} grade II) was 13% at 2 years, both for doses to the anterior rectal wall { 75 Gy (Figure). This is much lower than after conventional radiotherapy for prostate cancer (Smit et al.), where these figures were 21% and 60%, respectively. In univariate analyses, we did not find a significant relation between GI complications rates (grade II and/or III) and irradiated rectal wall volumes, total prescribed radiation dose or maximum radiation dose to the anterior rectal wall. The estimated NTCPs (on average 11%) were much higher than the incidence of grade III GI toxicity in our study ( =} grade II. In patients with an estimated NTCP between 0% and 10%, the incidence of complications {>=} grade II was 9.5%; for NCTPs of 10%-20%, and > 20% these figures were 11.4% and 0%, respectively. We are currently investigating whether dose surface histograms are more reliable to predict the observed late GI complications {>=} grade II. Conclusions: Conformal radiotherapy reduces late rectal complications significantly with respect to conventional radiotherapy. Observed late GI complications grade III were much lower than the NTCP estimations based on the model and parameter values of Kutcher et al. and Burman et al., respectively. Observed late GI complications {>=} grade II were overall in the range of the NTCP estimations, but did not correlate specifically with DVH parameters and NTCP estimations. Consequently, adaptation of the NTCP model and/or its parameter values for rectum complications is highly necessary. Grade III GU complications were mostly related to the prostatic urethra and consequently DVHs of the bladder have only limited value.

Incidence of and factors related to late complications in conformal and conventional radiation treatment of cancer of the prostate

The fundament hypothesis of conformal radiation therapy is that tumor control can be increased by using conformal treatment techniques that allow a higher tumor dose while maintaining an acceptable level of complications. To test this hypothesis, it is necessary first to estimate the incidence of morbidity for both standard and conformal fields. In this study, we examine factors that influence the incidence of late Grade 3 and 4 morbidity in patients treated with conformal and standard radiation treatment for prostate cancer. Six hundred sixteen consecutive patients treated with conformal or standard techniques between 1986 and 1994 to doses greater than 65 Gy and with more than 3 months follow-up were analyzed. No patients treated with prostatectomies were included in the analysis. The conformal technique includes special immobilization by a cast, careful identification of the target volume in three dimensions, localization of the inferior border of the prostate using a retrograde urethrogram, and individually shaped portals that conform to the Planning Target Volume (PTV). Multivariate analysis using a proportional hazards model compares differences in the incidence of Radiation Therapy Oncology Group/European Organization for Research and Center Treatment (RTOG/EORTC) Grade 3 and 4 late gastrointestinal (GI) and genitourinary (GU) morbidity by technique, T-stage, grade, age, hormonal treatment, irradiated volume, dose, and comorbid conditions. Grade 3 rectal bleeding was defined as requiring three or more cautery procedures. The overall actuarial incidence of genitourinary (GU) toxicities at 5 years was 3.4%, with the crude incidence being six cases in 616 patients satisfying the selection criteria; for gastrointestinal (GI) toxicities, the overall actuarial incidence was 2.7%, with the crude incidence being 13 cases out of 616 patients. The average time to complication for our patients was 12.8 months for GI toxicity and 32.9 months for GU toxicity (p < 0.001). No factors were found that were predictive for GU morbidity. The only factors significantly related to incidence of late GI morbidity on multivariate analysis of our data were dose and age. The central axis dose was a more significant variable than the dose prescribed to the Treated Volume. Age was negatively correlated with late GI morbidity, with older patients having a reduced incidence of toxicity. The median tolerance dose for GI complications was estimated to be 92.8 Gy, and the dose for 10% incidence was estimated to be 80.2 Gy. Treating the pelvis to 45 Gy did not increase the incidence of late morbidity. Late GI and GU toxicities were not correlated. The conformal technique has been associated with fewer acute Grade 2 toxicities (6). The use of conformal fields did not decrease the incidence of late GI morbidity; however, patients with this technique invariably had higher doses. Because of the dose response for this complication and the correlation between the dose and the use of conformal fields, one would not expect to demonstrate an advantage to conformal fields in this data set. On the other hand, no dose effect was observed for late GU morbidity. In this case, there appears to be an advantage for conformal treatment that has not reached statistical significance because the follow-up time is shorter than for the patients treated with conventional fields and the latency for GU morbidity is long.