Early hematologic changes during prostate cancer radiotherapy predictive for late urinary and bowel toxicity.

BACKGROUND: The primary objective of the study was to identify early hematologic changes predictive for radiotherapy (RT)-associated genitourinary and gastrointestinal toxicity. METHODS: In a group of 91 prostate cancer patients presenting for primary (n = 51) or postoperative (n = 40) curative RT, blood samples (blood count, acute phase proteins, and cytokines) were analyzed before (T1), three times during (T2-T4), and 6-8 weeks after (T5) radiotherapy. Before RT (baseline), on the last day (acute toxicity), a median of 2 months and 16 months (late toxicity) after RT, patients responded to a validated questionnaire (Expanded Prostate Cancer Index Composite). Acute score changes > 20 points and late changes > 10 points were considered clinically relevant. RESULTS: Radiotherapy resulted in significant changes of hematologic parameters, with the largest effect on lymphocytes (mean decrease of 31-45 %) and significant dependence on target volume. C-reactive protein (CRP) elevation > 5 mg/l and hemoglobin level decrease ≥ 5 G/1 at T2 were found to be independently predictive for acute urinary toxicity (p < 0.01, respectively). CRP elevation was predominantly detected in primary prostate RT (p = 0.02). Early lymphocyte level elevation ≥ 0.3G/l at T2 was protective against late urinary and bowel toxicity (p = 0.02, respectively). Other significant predictive factors for late bowel toxicity were decreasing hemoglobin levels (cut-off ≥ 5 G/l) at T2 (p = 0.04); changes of TNF-α (tumor necrosis factor; p = 0.03) and ferritin levels (p = 0.02) at T5. All patients with late bowel toxicity had interleukin (IL)-6 levels < 1.5 ng/l at T2 (63 % without; p = 0.01). CONCLUSION: Early hematologic changes during prostate cancer radiotherapy are predictive for late urinary and bowel toxicity.

Hematologic changes during prostate cancer radiation therapy are dependent on the treatment volume.

AIM: To assess hematologic changes of modern prostate radiation therapy (RT) comparing different target volumes. PATIENTS & METHODS: Blood samples were evaluated before (T1), during (T2-T4) and 6-8 weeks after (T5) RT in a group of 113 patients. Whole-pelvic RT up to 46 Gy was applied in 27 cases. The total dose to the prostatic fossa (n = 46)/prostate (n = 67) was 66/76 Gy. RESULTS: Erythrocyte, leukocyte and platelet levels decreased significantly relative to baseline levels at T2-T5. Neoadjuvant hormonal therapy had an impact on hemoglobin levels before and during RT. The cumulative incidence of grade 2 leukopenia was 15 versus 2% (p = 0.02) and grade 2 anemia 8 versus 0% (p = 0.03) with versus without whole-pelvic RT, respectively. Lymphocyte decrease was larger at times T2-T5 (36 vs 3% grade 3 toxicity; p < 0.01). CONCLUSION: Prostate RT has a small but significant and longer effect on the blood count. Lower lymphocyte levels need to be considered when larger volumes are treated.

Transurethral resection of the prostate after radiotherapy for prostate cancer: impact on quality of life.

OBJECTIVES: To evaluate the impact of transurethral resection of the prostate on quality of life after radiotherapy for prostate cancer. METHODS: A group of 49 consecutive patients with and 487 without prior transurethral resection of the prostate responded to the Expanded Prostate Cancer Index Composite questionnaire before, on the last day, and a median time of 2 months and 16 months after external beam radiotherapy (70-78 Gy). A matched-pair analysis was used to avoid the influence of treatment-associated confounding factors, including dose, treatment volume and hormonal therapy. RESULTS: Significantly smaller acute urinary score changes relative to baseline levels resulted with versus without prior transurethral resection of the prostate (mean function/bother score decrease of 3/6 vs 18/21 points at the end of radiotherapy; P < 0.01), affecting urinary incontinence (pads to control urinary leakage in 4% vs 24%; P = 0.03) and irritative/obstructive symptoms (big/moderate problem with weak urinary stream in 11% vs 37%; P = 0.02). As opposed to acute changes, transurethral resection of the prostate was a significant predisposing factor for a long-term urinary function score decrease >10 points (20% vs 6% of patients with vs without prior resection; P = 0.04). Urinary incontinence risk was higher for patients with a longer time from resection to radiotherapy. CONCLUSIONS: Transurethral resection of the prostate significantly affects acute (considerably fewer symptoms) and long-term (relevant toxicity in some cases) urinary quality of life after radiotherapy for prostate cancer.

Learning curve in the application of a hydrogel spacer to protect the rectal wall during radiotherapy of localized prostate cancer.

OBJECTIVE: To evaluate the effect of increasing experience on hydrogel dimensions, rectal dose, and acute toxicity, and to discuss important technical issues gained from this experience. METHODS: Sixty-four consecutive patients with prostate cancer were included in this analysis (G1/G2 corresponding to first/second 32 patients) after injection of 10 mL spacer gel. All patients were treated with a 5-field intensity-modulated radiotherapy technique to 76-78 Gy. Treatment toxicity was evaluated with a validated quality of life questionnaire (expanded prostate cancer index composite) before and after radiotherapy. RESULTS: Rectum volume could be entirely excluded from the planning target volume in 31% in G1 vs 56% in G2 (P = .04). Increasing symmetry was detected comparing the first 15 patients to the subsequent rest, with mean differences between right and left of 0.6 cm vs 0.3 cm at the midgland (P = .03). Mean distance between prostate and anterior rectal wall increased from 0.8 cm/1.1 cm/0.8 cm (G1) at the base/middle/apex to 1.3 cm/1.5 cm/1.2 cm (G2), respectively, so that the dose to the rectum decreased significantly (6% vs 2% of the volume inside the 70 Gy isodose; P <.01). Bowel function and bother score changes were smaller comparing baseline with last day of radiotherapy levels (mean 16/18 in G1 vs 9/12 in G2). CONCLUSION: A learning curve could be demonstrated in our patient population, respecting improved and more symmetrical spacer placement, improved treatment planning, and less treatment-related acute toxicity. Several important technical aspects need to be considered.

Spacer stability and prostate position variability during radiotherapy for prostate cancer applying a hydrogel to protect the rectal wall.

BACKGROUND AND PURPOSE: The aim was to evaluate the spacer dimensions and prostate position variability during the course of radiotherapy for prostate cancer. MATERIALS AND METHODS: CT scans were performed in a group of 15 patients (G1) after the 10 ml injection of a hydrogel spacer (SpaceOAR™) and 30 patients without a spacer (G2) before the beginning of treatment (CT1) and in the last treatment week, 10-12 weeks following spacer implantation (CT2). Spacer dimensions and displacements were determined and prostate displacements compared. RESULTS: Mean volume of the hydrogel increased slightly (17%; p<0.01), in 4 of 15 patients >2 cm(3). The average displacement of the hydrogel center of mass was 0.6mm (87%≤ 2.2mm), -0.6mm (100% ≤ 2.2mm) and 1.4mm (87% ≤ 4.3mm) in the x-, y- and z-axes (not significant). The average distance between prostate and anterior rectal wall before/at the end of radiotherapy was 1.6 cm/1.5 cm, 1.2 cm/1.3 cm and 1.0 cm/1.1cm at the level of the base, middle and apex (G1). Prostate position variations were similar comparing G1 and G2, but significant systematic posterior displacements were only found in G2. CONCLUSIONS: A stable distance between the prostate and anterior rectal wall results during the radiotherapy course after injection of the spacer before treatment planning. Larger posterior prostate displacements could be reduced.

Local prostate cancer radiotherapy after prostate-specific antigen progression during primary hormonal therapy.

BACKGROUND: The outcome of patients after radiotherapy (RT) for localized prostate cancer in case of prostate-specific antigen (PSA) progression during primary hormonal therapy (HT) is not well known. METHODS: A group of 27 patients presenting with PSA progression during primary HT for local prostate cancer RT was identified among patients who were treated in the years 2000-2004 either using external-beam RT (EBRT; 70.2 Gy; n=261) or Ir-192 brachytherapy as a boost to EBRT (HDR-BT; 18 Gy + 50.4 Gy; n=71). The median follow-up period after RT was 68 months. RESULTS: Median biochemical recurrence free (BRFS), disease specific (DSS) and overall survival (OS) for patients with PSA progression during primary HT was found to be only 21, 54 and 53 months, respectively, with a 6-year BRFS, DSS and OS of 19%, 41% and 26%. There were no significant differences between different RT concepts (6-year OS of 27% after EBRT and 20% after EBRT with HDR-BT).Considering all 332 patients in multivariate Cox regression analysis, PSA progression during initial HT, Gleason score>6 and patient age were found to be predictive for lower OS (p<0.001). The highest hazard ratio resulted for PSA progression during initial HT (7.2 in comparison to patients without PSA progression during primary HT). PSA progression and a nadir >0.5 ng/ml during initial HT were both significant risk factors for biochemical recurrence. CONCLUSIONS: An unfavourable prognosis after PSA progression during initial HT needs to be considered in the decision process before local prostate radiotherapy. Results from other centres are needed to validate our findings.

Dose-escalation using intensity-modulated radiotherapy for prostate cancer - evaluation of quality of life with and without (18)F-choline PET-CT detected simultaneous integrated boost.

BACKGROUND: In comparison to the conventional whole-prostate dose escalation, an integrated boost to the macroscopic malignant lesion might potentially improve tumor control rates without increasing toxicity. Quality of life after radiotherapy (RT) with vs. without (18)F-choline PET-CT detected simultaneous integrated boost (SIB) was prospectively evaluated in this study. METHODS: Whole body image acquisition in supine patient position followed 1 h after injection of 178-355MBq (18)F-choline. SIB was defined by a tumor-to-background uptake value ratio > 2 (GTV(PET)). A dose of 76Gy was prescribed to the prostate (PTV(prostate)) in 2Gy fractions, with or without SIB up to 80Gy. Patients treated with (n = 46) vs. without (n = 21) SIB were surveyed prospectively before (A), at the last day of RT (B) and a median time of two (C) and 19 month (D) after RT to compare QoL changes applying a validated questionnaire (EPIC - expanded prostate cancer index composite). RESULTS: With a median cut-off standard uptake value (SUV) of 3, a median GTV(PET) of 4.0 cm(3) and PTV(boost) (GTV(PET) with margins) of 17.3 cm(3) was defined. No significant differences were found for patients treated with vs. without SIB regarding urinary and bowel QoL changes at times B, C and D (mean differences ≤3 points for all comparisons). Significantly decreasing acute urinary and bowel score changes (mean changes > 5 points in comparison to baseline level at time A) were found for patients with and without SIB. However, long-term urinary and bowel QoL (time D) did not differ relative to baseline levels - with mean urinary and bowel function score changes < 3 points in both groups (median changes = 0 points). Only sexual function scores decreased significantly (> 5 points) at time D. CONCLUSIONS: Treatment planning with (18)F-choline PET-CT allows a dose escalation to a macroscopic intraprostatic lesion without significantly increasing toxicity.

Application of a spacer gel to optimize three-dimensional conformal and intensity modulated radiotherapy for prostate cancer.

BACKGROUND AND PURPOSE: The aim was to evaluate the impact of a spacer gel on the dose distribution, applying three-dimensional conformal (3D CRT) and intensity modulated radiotherapy (IMRT) planning techniques. MATERIAL AND METHODS: The injection of a spacer gel (10 ml SpaceOAR™) was performed between the prostate and rectum under transrectal ultrasound guidance in 18 patients with prostate cancer. 3D CRT and IMRT treatment plans were compared based on CT before and after injection (78 Gy prescription dose). RESULTS: In contrast to the PTV and bladder, significant advantages (p<0.01) resulted in respect of all analysed rectal dose values comparing pre spacer with post spacer plans for both techniques. Rectal NTCP (normal tissue complication probability) reached the lowest percentage after spacer injection irrespective of the technique, with a mean reduction of >50% for both IMRT and 3D CRT. Significantly (p<0.01) higher D(mean), and V(78) for the PTV were reached with IMRT vs. 3D CRT plans, with a smaller rectum V(76) but larger rectum V(50). CONCLUSIONS: The injection of a spacer gel between the prostate and anterior rectal wall is associated with considerably lower doses to the rectum and consequentially lower NTCP values irrespective of the radiotherapy technique.

Combination of dose escalation with technological advances (intensity-modulated and image-guided radiotherapy) is not associated with increased morbidity for patients with prostate cancer.

PURPOSE: The aim was to evaluate treatment-related morbidity after intensity-modulated (IMRT) and image-guided (IGRT) radiotherapy with a total dose of 76 Gy in comparison to conventional conformal radiotherapy (3DCRT) up to 70.2-72 Gy for patients with prostate cancer. PATIENTS AND METHODS: All patients were prospectively surveyed prior to, on the last day, as well as after a median time of 2 and 16 months after RT using a validated questionnaire (Expanded Prostate Cancer Index Composite). Criteria for the 78 matched pairs after IMRT vs. 3DCRT were patient age, use of antiandrogens, treatment volume (± whole pelvis), prognostic risk group, and urinary/bowel/sexual quality of life (QoL) before treatment. RESULTS: QoL changes after dose-escalated IMRT were found to be similar to QoL changes after 3DCRT in all domains. Only sexual function scores more than 1 year after RT decreased slightly more after 3DCRT in comparison to IMRT (mean 9 vs. 6 points; p = 0.04), with erections firm enough for intercourse in 14% vs. 30% (p = 0.03). Painful bowel movements were reported more frequently after 3DCRT vs. IMRT 2 months after treatment (≥ once a day in 10% vs. 1%; p = 0.03), but a tendency for higher rectal bleeding rates was found after IMRT vs. 3DCRT more than 1 year after RT (≥ rarely in 20% vs. 9%; p = 0.06). CONCLUSION: Combination of dose escalation with technological advances (IMRT and IGRT) is not associated with increased morbidity for patients with prostate cancer.