Karin Fischedick

Erectile Dysfunction After External Beam Radiotherapy for Prostate Cancer

BACKGROUND There is a lack of prospective studies focusing on the sexual quality of life of prostate cancer patients after conformal radiotherapy (RT). OBJECTIVE To evaluate the incidence, progression, and predictive factors for erectile dysfunction (ED). DESIGN, SETTING AND PARTICIPANTS Patients who responded to the sexual domain of the Expanded Prostate Cancer Index Composite (EPIC) questionnaire before and more than 1 yr after RT and never received an antiandrogen treatment were included (n=123). INTERVENTION RT dose was 70.2-72 Gy. Eleven patients used a phosphodiesterase-5 (PDE-5) inhibitor. MEASUREMENTS Patients responded to the EPIC questionnaire before (time A), at the last day (B), a median time of 2 mo after (C), and 16 mo after (D) RT. In a multivariate analysis, risk factors (patient age, prostate volume, planning target volume, use of PDE-5 inhibitor, comorbidities) were tested for their independent effects on ED before and after RT. RESULTS AND LIMITATIONS Sexual function and bother scores had already decreased by the end of RT (median function and bother scores at times A/B/C/D: 41/30/32/24 and 75/50/50/50). Initial function scores correlated well with late function scores (r=0.7; p<0.001). The ability to have an erection was reported by 81%/72%/74%/60% (preserved erectile ability in 70% at time D), erections firm enough for sexual intercourse by 44%/33%/35%/27% (preserved erections sufficient for intercourse in 53% at time D) of patients. A higher patient age and diabetes were predictive of both a pre-existing ED and a post-RT acquired ED. Nightly erections before treatment proved prognostically favourable (at least weekly vs. < weekly-hazard ratio of 5.9 for preserved erections sufficient for intercourse; p=0.01). Higher rates of ED can be expected with longer follow-up. CONCLUSIONS The incidence of ED progressively increases after RT. Patient age and diabetes are risk factors for both pre-treatment and RT-associated ED. Nightly erections before RT proved prognostically favourable.

Consequential late effects after radiotherapy for prostate cancer - a prospective longitudinal quality of life study.

BackgroundTo answer the question if and to which extent acute symptoms at the end and/or several weeks after radiotherapy can predict adverse urinary and gastrointestinal long-term quality of life (QoL).MethodsA group of 298 patients has been surveyed prospectively before (time A), at the last day (B), two months after (C) and >one year after (D) radiotherapy using a validated questionnaire (Expanded Prostate Cancer Index Composite). A subgroup of 10% with the greatest urinary/bowel bother score decrease at time D was defined as patients with adverse long-term QoL.ResultsSubgroup and correlation analyses could demonstrate a strong dependence of urinary/bowel QoL after radiotherapy on urinary/bowel QoL before radiotherapy. In contrast to absolute scores, QoL score changes (relative to baseline scores) did not correlate with pretreatment scores. Long-term changes could be well predicted by acute changes. Patients reporting great/moderate bother with urinary/bowel problems at time C reported to have great/moderate bother at time D in ≥ 50%, respectively. In a multivariate analysis of factors for adverse long-term urinary and bowel QoL, score changes at time C were found to be independent predictors, respectively. Additionally, QoL changes at time B were independently predictive for adverse long-term bowel QoL.ConclusionsConsequential late effects play a major role after radiotherapy for prostate cancer. Patients with greater and particularly longer non-healing acute toxicity are candidates for closer follow-up and possible prophylactic actions to reduce a high probability of long-term problems.

Impact of age and comorbidities on health-related quality of life for patients with prostate cancer: evaluation before a curative treatment

BackgroundInterpretation of comparative health-related quality of life (HRQOL) studies following different prostate cancer treatments is often difficult due to differing patient ages. Furthermore, age-related changes can hardly be discriminated from therapy-related changes. The evaluation of age-and comorbidity-related changes was in focus of this study.MethodsHRQOL of 528 prostate cancer patients was analysed using a validated questionnaire (Expanded Prostate Cancer Index Composite) before a curative treatment. Patients were divided into age groups ≤65, 66-70, 71-75 and >75 years. The impact of specific comorbidities and the Charlson Comorbidity Index (CCI) were evaluated. The questionnaire comprises 50 items concerning the urinary, bowel, sexual and hormonal domains for function and bother. For assessment of sexual and hormonal domains, only patients without prior hormonal treatment were included (n = 336).ResultsUrinary incontinence was observed increasingly with higher age (mean function scores of 92/88/85/87 for patients ≤65, 66-70, 71-75 and >75 years) - complete urinary control in 78%/72%/64%/58% (p < 0.01). Sexual function scores decreased particularly (48/43/35/30), with erections sufficient for intercourse in 68%/50%/36%/32% (p < 0.01) - a decrease of more than a third comparing patients ≤65 vs. 66-70 (36%) and 66-70 vs. 71-75 years (39%). The percentage of patients with comorbidities was lowest in the youngest group (48% vs. 66%/68%/63% for ages 66-70/71-75/>75 years; p < 0.05). A multivariate analysis revealed an independent influence of both age and comorbidities on urinary incontinence, specifically diabetes on urinary bother, and both age and diabetes on sexual function/bother. Rectal domain scores were not significantly influenced by age or comorbidities. A CCI>5 particularly predisposed for lower urinary and sexual HRQOL scores.ConclusionUrinary continence and sexual function are the crucial HRQOL domains with age-related and independently comorbidity-related decreasing scores. The results need to be considered for the interpretation of comparative studies or longitudinal changes after a curative treatment.

Factor Analysis of the Expanded Prostate Cancer Index Composite in a Patient Group after Primary (External Beam Radiotherapy and Permanent Iodine-125 Brachytherapy) and Postoperative Radiotherapy for Prostate Cancer

Background: The Expanded Prostate Cancer Index Composite questionnaire is widely used as a comprehensive assessment of health-related quality of life issues in prostate cancer management, distinguishing urinary, bowel, sexual, hormonal domains. The primary purpose of this study was to assess the factor structure of this questionnaire. Patients and Methods: A principal component analysis with orthogonal (varimax) rotation was conducted on data collected from 418 patients after primary (external beam radiotherapy and permanent iodine-125 brachytherapy) and postoperative radiotherapy for prostate cancer. Results: Health-related quality of life scores well demonstrated differences in subpopulations before radiotherapy and different toxicity profiles of specific radiotherapy concepts. The extraction of 12 factors accounted for 75.5% of the variance. With exception of the sexual domain, a strong dependence between the function in a domain and the related bother was found. The concept to discriminate urinary incontinence and urinary irritation/ obstruction subscales was supported. However, the items ‘bleeding with urination’ and ‘bloody stools’ have loaded on separate factors. After separation of the items of the function and bother subscales, a 4-factor solution was confirmed to be optimal, respectively. Conclusion: The obtained factor structure corresponds to the original Expanded Prostate Cancer Index Composite subscales. Minor divergences have been found, depicting especially items concerning ‘incontinence’ and ‘bleeding’ as distinct aspects of a domain.

Health-related quality of life after permanent interstitial brachytherapy for prostate cancer: correlation with postimplant CT scan parameters.

Purpose:To determine dosimetric risk factors for increased toxicity after permanent interstitial brachytherapy for prostate cancer.Patients and Methods:Quality of life questionnaires (Expanded Prostate Cancer Index Composite) of 60 and 56 patients were analyzed after a median posttreatment time of 6 weeks (A—acute) and 16 months (L—late). The corresponding CT scans were performed 30 days after the implant. The prostate, rectal wall, and base of seminal vesicles were contoured. Prostate volume, number of seeds and needles as well as dosimetric parameters were correlated with the morbidity scores.Results:For a prostate volume of 38 ± 12 cm3 (mean ± standard deviation), 54 ± 7 125I sources (Rapid Strands®, activity of 22.6 ± 3.0 MBq [0.61 ± 0.08 mCi]) were implanted using 20 ± 6 needles. Improved late urinary function scores resulted from a higher number of sources per cm3 (≥ 1.35). A prostate D90 < 170 Gy (A)/< 185 Gy (L) and base of seminal vesicle D10 < 190 Gy (A and L) were associated with higher urinary function scores. Late rectal function scores were significantly higher for patients with a prostate V200 < 50% and V150 < 75%. Patients with a prostate volume < 40 cm3 reached better sexual function scores (A and L). A higher number of needles per cm3 (≥ 0.5) resulted in improved late urinary, bowel and sexual function scores.Conclusion:Quality of life after a permanent implant can be improved by using an adequate amount of sources and needles. With an increasing number of seeds per cm3, dose homogeneity is improving. A prostate D90 < 170 Gy and a base of seminal vesicle D10 < 190 Gy (as an indicator of the dose to the bladder neck and urethral sphincter) can be recommended to maintain a satisfactory urinary function.Ziel:Analyse dosimetrischer Risikofaktoren für erhöhte Toxizitätsraten nach permanenter interstitieller Brachytherapie beim Prostatakarzinom.Patienten und Methodik:Fragebögen zur Lebensqualität (Expanded Prostate Cancer Index Composite) von 60 bzw. 56 Patienten wurden 6 Wochen (A—akut) und 16 Monate (S—spät) nach Therapie analysiert. Die entsprechenden Postimplantations-CTs wurden 30 Tage nach der Behandlung durchgeführt. Die Prostata, Rektumwand und Basis der Samenblasen wurden konturiert. Prostatavolumen, Seed- und Nadelanzahl sowie dosimetrische Parameter wurden mit den Punktwerten der Fragebögen korreliert.Ergebnisse:Zur Behandlung eines Prostatavolumens von 38 ± 12 cm3 (Mittelwert ± Standardabweichung) wurden 54 ± 7 125I-Seeds (Rapid Strands®) der Aktivität 22,6 ± 3,0 MBq (0,61 ± 0,08 mCi) über 20 ± 6 Nadeln implantiert. Verbesserte späte Blasenfunktionswerte resultierten bei einer höheren Seedanzahl pro cm3 (≥ 1,35). Ein Prostata-D90-Wert < 170 Gy (A)/< 185 Gy (S) und ein Samenblasen-D10-Wert < 190 Gy (A und S) waren mit verbesserten Blasenfunktionswerten assoziiert. Späte Funktionswerte für den Stuhlgang waren bei Patienten mit Prostata-V200-Werten < 50% und -V150-Werten < 75% signifikant höher. Patienten mit einem Prostatavolumen < 40 cm3 erreichten bessere Werte in der Sexualität (A und S). Eine höhere Nadelanzahl pro cm3 (≥ 0,5) resultierte in verbesserten späten Funktionswerten in allen Domänen.Schlussfolgerung:Die Lebensqualität nach permanenter Brachytherapie kann durch den Einsatz einer adäquaten Menge Seeds und Nadeln verbessert werden. Mit höherer Seedanzahl pro cm3 verbessert sich die Homogenität der Dosisverteilung. Ein Prostata-D90-Wert < 170 Gy und ein Samenblasen-D10-Wert < 190 Gy (als ein Indikator für die Dosisbelastung im Bereich des Blasenhalses und des Sphinkters) können zur Erhaltung einer guten Blasenfunktion empfohlen werden.

Health-Related Quality of Life after Permanent Interstitial Brachytherapy for Prostate Cancer

Purpose:To determine dosimetric risk factors for increased toxicity after permanent interstitial brachytherapy for prostate cancer.Patients and Methods:Quality of life questionnaires (Expanded Prostate Cancer Index Composite) of 60 and 56 patients were analyzed after a median posttreatment time of 6 weeks (A—acute) and 16 months (L—late). The corresponding CT scans were performed 30 days after the implant. The prostate, rectal wall, and base of seminal vesicles were contoured. Prostate volume, number of seeds and needles as well as dosimetric parameters were correlated with the morbidity scores.Results:For a prostate volume of 38 ± 12 cm3 (mean ± standard deviation), 54 ± 7 125I sources (Rapid Strands®, activity of 22.6 ± 3.0 MBq [0.61 ± 0.08 mCi]) were implanted using 20 ± 6 needles. Improved late urinary function scores resulted from a higher number of sources per cm3 (≥ 1.35). A prostate D90 < 170 Gy (A)/< 185 Gy (L) and base of seminal vesicle D10 < 190 Gy (A and L) were associated with higher urinary function scores. Late rectal function scores were significantly higher for patients with a prostate V200 < 50% and V150 < 75%. Patients with a prostate volume < 40 cm3 reached better sexual function scores (A and L). A higher number of needles per cm3 (≥ 0.5) resulted in improved late urinary, bowel and sexual function scores.Conclusion:Quality of life after a permanent implant can be improved by using an adequate amount of sources and needles. With an increasing number of seeds per cm3, dose homogeneity is improving. A prostate D90 < 170 Gy and a base of seminal vesicle D10 < 190 Gy (as an indicator of the dose to the bladder neck and urethral sphincter) can be recommended to maintain a satisfactory urinary function.Ziel:Analyse dosimetrischer Risikofaktoren für erhöhte Toxizitätsraten nach permanenter interstitieller Brachytherapie beim Prostatakarzinom.Patienten und Methodik:Fragebögen zur Lebensqualität (Expanded Prostate Cancer Index Composite) von 60 bzw. 56 Patienten wurden 6 Wochen (A—akut) und 16 Monate (S—spät) nach Therapie analysiert. Die entsprechenden Postimplantations-CTs wurden 30 Tage nach der Behandlung durchgeführt. Die Prostata, Rektumwand und Basis der Samenblasen wurden konturiert. Prostatavolumen, Seed- und Nadelanzahl sowie dosimetrische Parameter wurden mit den Punktwerten der Fragebögen korreliert.Ergebnisse:Zur Behandlung eines Prostatavolumens von 38 ± 12 cm3 (Mittelwert ± Standardabweichung) wurden 54 ± 7 125I-Seeds (Rapid Strands®) der Aktivität 22,6 ± 3,0 MBq (0,61 ± 0,08 mCi) über 20 ± 6 Nadeln implantiert. Verbesserte späte Blasenfunktionswerte resultierten bei einer höheren Seedanzahl pro cm3 (≥ 1,35). Ein Prostata-D90-Wert < 170 Gy (A)/< 185 Gy (S) und ein Samenblasen-D10-Wert < 190 Gy (A und S) waren mit verbesserten Blasenfunktionswerten assoziiert. Späte Funktionswerte für den Stuhlgang waren bei Patienten mit Prostata-V200-Werten < 50% und -V150-Werten < 75% signifikant höher. Patienten mit einem Prostatavolumen < 40 cm3 erreichten bessere Werte in der Sexualität (A und S). Eine höhere Nadelanzahl pro cm3 (≥ 0,5) resultierte in verbesserten späten Funktionswerten in allen Domänen.Schlussfolgerung:Die Lebensqualität nach permanenter Brachytherapie kann durch den Einsatz einer adäquaten Menge Seeds und Nadeln verbessert werden. Mit höherer Seedanzahl pro cm3 verbessert sich die Homogenität der Dosisverteilung. Ein Prostata-D90-Wert < 170 Gy und ein Samenblasen-D10-Wert < 190 Gy (als ein Indikator für die Dosisbelastung im Bereich des Blasenhalses und des Sphinkters) können zur Erhaltung einer guten Blasenfunktion empfohlen werden.

Quality of Life After Whole Pelvic Versus Prostate-Only External Beam Radiotherapy for Prostate Cancer: A Matched-Pair Comparison

PURPOSE Comparison of health-related quality of life after whole pelvic (WPRT) and prostate-only (PORT) external beam radiotherapy for prostate cancer. METHODS AND MATERIALS A group of 120 patients (60 in each group) was surveyed prospectively before radiation therapy (RT) (time A), at the last day of RT (time B), at a median time of 2 months (time C) and >1 year after RT (time D) using a validated questionnaire (Expanded Prostate Cancer Index Composite). All patients were treated with 1.8- to 2.0-Gy fractions up to 70.2 to 72.0 Gy with or without WPRT up to 45 to 46 Gy. Pairs were matched according to the following criteria: age±5 years, planning target volume±10 cc (considering planning target volume without pelvic nodes for WPRT patients), urinary/bowel/sexual function score before RT±10, and use of antiandrogens. RESULTS With the exception of prognostic risk factors, both groups were well balanced with respect to baseline characteristics. No significant differences were found with regard to urinary and sexual score changes. Mean bladder function scores reached baseline levels in both patient subgroups after RT. However, bowel function scores decreased significantly more for patients after WPRT than in those receiving PORT at all times (p<0.01, respectively). Significant differences were found for most items in the bowel domain in the acute phase. At time D, patients after WPRT reported rectal urgency (>once a day in 15% vs. 3%; p=0.03), bloody stools (≥half the time in 7% vs. 0%; p=0.04) and frequent bowel movements (>two on a typical day in 32% vs. 7%; p<0.01) more often than did patients after PORT. CONCLUSION In comparison to PORT, WPRT (larger bladder and rectum volumes in medium dose levels, but similar volumes in high dose levels) was associated with decreased bowel quality of life in the acute and chronic phases after treatment but remained without adverse long-term urinary effects.

Rectal dosimetry following prostate brachytherapy with stranded seeds – Comparison of transrectal ultrasound intra-operative planning (day 0) and computed tomography-postplanning (day 1 vs. day 30) with special focus on sources placed close to the rectal wall

BACKGROUND AND PURPOSE The aim of the study was to compare intra-operative and postplanning at different intervals with special focus on sources placed close to the rectal wall. MATERIALS AND METHODS In 61 consecutive patients, CT scans were performed on day 1 and day 30 after an I-125 implant with stranded seeds. The number of sources < or =7 mm to the rectal wall was determined, and displacements were analyzed. The angulation of strands relative to rectal wall was compared between intra-operative transrectal ultrasound (TRUS) and both postplanning CT scans. RESULTS Sources close to the rectum on day 1 (n=204) have been the most apical in a strand in 98.5% (n=201). By comparing day 1 and day 30 data, significant inferior source displacements (mean 3.6 mm; p=0.02) relative to pelvic bones and a decreasing distance to the rectal wall (mean 1.2 mm; p<0.01)--consequentially increasing rectal dose--were determined only for sources initially > or =3 mm to the rectum. In contrast to an almost parallel arrangement of the needle track and the rectal wall in TRUS, strands and rectal wall converged towards the apex in the postplanning CT scans (mean >30 degrees). CONCLUSIONS Posterior preplanning margins around the prostate should be particularly limited at the level of the prostate apex.

Self-assessed bowel toxicity after external beam radiotherapy for prostate cancer - predictive factors on irritative symptoms, incontinence and rectal bleeding

BackgroundThe aim of the study was to evaluate self-assessed bowel toxicity after radiotherapy (RT) for prostate cancer. In contrast to rectal bleeding, information concerning irritative symptoms (rectal urgency, pain) and incontinence after RT has not been adequately documented and reported in the past.MethodsPatients (n = 286) have been surveyed prospectively before (A), at the last day (70.2-72.0 Gy; B), a median time of two (C) and 16 months after RT (D) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Bowel domain score changes were analyzed and patient-/dose-volume-related factors tested for a predictive value on three separate factors (subscales): irritative symptoms, incontinence and rectal bleeding.ResultsIrritative symptoms were most strongly affected in the acute phase, but the scores of all subscales remained slightly lower at time D in comparison to baseline scores. Good correlations (correlation indices >0.4; p < 0.001 for all) were found between irritative and incontinence function/bother scores at times B-D, suggesting the presence of an urge incontinence for the majority of patients who reported uncontrolled leakage of stool. Planning target volume (PTV), haemorrhoids and stroke in past history were found to be independent predictive factors for rectal bleeding at time D. Chronic renal failure predisposed for lower irritative scores at time D. Paradoxically, patients with greater rectum volumes inside higher isodose levels presented with higher quality of life scores in the irritative and incontinence subscales.ConclusionPTV and specific comorbidities are important predictive factors on adverse bowel quality of life changes after RT for prostate cancer. However, greater rectum volumes inside high isodose levels have not been found to be associated with lower quality of life scores.

Neoadjuvant hormonal therapy and external-beam radiotherapy versus external-beam irradiation alone for prostate cancer

Purpose:To evaluate the impact of neoadjuvant hormonal therapy (NHT) on quality of life after external-beam radiotherapy (EBRT) for prostate cancer.Patients and Methods:A group of 170 patients (85 with and 85 without NHT) has been surveyed prospectively before EBRT (70.2–72 Gy), at the last day of EBRT, a median time of 2 months and 15 months after EBRT using a validated questionnaire (Expanded Prostate Cancer Index Composite). Pairs with and without NHT (median treatment time of 3.5 months before EBRT) were matched according to the respective planning target volume and prostate volume.Results:Before EBRT, significantly lower urinary function/bother, sexual function and hormonal function/bother scores were found for patients with NHT. More than 1 year after EBRT, only sexual function scores remained lower. In a multivariate analysis, NHT and adjuvant hormonal therapy (HT) versus NHT only (hazard ratio 14; 95% confidence interval 2.7–183; p = 0.02) and luteinizing hormone-releasing hormone (LHRH) agonists versus antiandrogens (hazard ratio 3.6; 95% confidence interval 1.1–12; p = 0.04) proved to be independent risk factors for long-term erectile dysfunction (no or very poor ability to have an erection).Conclusion:With the exception of sexual function (additional adjuvant HT and application of LHRH analog independently adverse), short-term NHT was not found to decrease quality of life after EBRT for prostate cancer.Ziel:Untersuchung des Einflusses einer neoadjuvanten Hormontherapie (NHT) auf die Lebensqualität nach perkutaner Radiotherapie (EBRT) beim Prostatakarzinom.Patienten und Methodik:In einer Gruppe von 170 Patienten (85 mit und 85 ohne NHT) wurde die Lebensqualität prospektiv vor EBRT (70,2–72 Gy), am letzten Tag der EBRT, median 2 Monate und 15 Monate nach EBRT mittels eines validierten Fragebogens (Expanded Prostate Cancer Index Composite) erfasst. Paare mit und ohne NHT (median 3,5 Monate vor EBRT verabreicht) wurden entsprechend dem jeweiligen Planungszielvolumen und Prostatavolumen gematcht.Ergebnisse:Vor EBRT zeigten sich bei Patienten mit NHT signifikant schlechtere Funktions- und Belastungswerte in den Domänen Wasserlassen, Sexualität und hormonelle Beschwerden. Über 1 Jahr nach Ende der EBRT blieb nur noch die sexuelle Funktion signifikant schlechter. In einer multivariaten Analyse zeigte sich der unabhängige Einfluss der NHT mit adjuvanter Hormontherapie (HT) versus alleiniger NHT (relatives Risiko 14; 95%-Konfidenzintervall 2,7–183; p = 0,02) und der Gonadotropin-releasing-Hormon-(GnRH-)Analoga versus Antiandrogene (relatives Risiko 3,6; 95%-Konfidenzintervall 1,1–12; p = 0,04) als Risikofaktoren für die längerfristige erektile Dysfunktion (keine oder sehr geringe Erektionsfähigkeit).Schlussfolgerung:Mit Ausnahme des Einflusses auf die sexuellen Funktionswerte (zusätzliche adjuvante HT und Verwendung von GnRH-Analoga unabhängig voneinander nachteilig) zeigte die kurzzeitige NHT keine negativen Auswirkungen auf die Lebensqualität nach EBRT des Prostatakarzinoms.