Teresa L. Bruno

Late rectal complications after prostate brachytherapy for localized prostate cancer

This review of the literature on late rectal complications after prostate brachytherapy indicated that it is a highly effective treatment modality for patients with clinically localized prostate cancer but can cause chronic radiation proctitis. The most common manifestation of chronic radiation proctitis was anterior rectal wall bleeding, which often occurred within the first 2 years after brachytherapy. It is interesting to note that the rates of late rectal morbidity appear to have declined over time, which may reflect improvements in implantation techniques and imaging. Rectal biopsy as part of the workup to evaluate rectal bleeding can lead to rectal fistula and the need for colostomy, a rare but major complication. The authors recommend 1) screening colonoscopy before brachytherapy for patients who have not had a screening colonoscopy within the preceding 3 years to rule out colorectal malignancies and, thus, facilitate conservative management should rectal bleeding occur; 2) lifestyle modifications during treatment to limit exposure of the rectum to radiation; and 3) conservative management for rectal bleeding that occurs within 2 years after brachytherapy. Cancer 2009.

Urinary Side Effects and Complications After Permanent Prostate Brachytherapy: The MD Anderson Cancer Center Experience

OBJECTIVES To evaluate acute and long-term urinary morbidity after permanent prostate brachytherapy at a single tertiary care center. To minimize the risk of long-term urinary morbidity, it is important for clinicians to be able to distinguish acute urinary side effects after prostate brachytherapy from longer-term treatment-related urinary complications. METHODS The medical records of 351 consecutive patients who underwent prostate brachytherapy at the MD Anderson Cancer Center between 1998 and 2006 were analyzed. To evaluate the short-term urinary side effects, the Expanded Prostate Cancer Index Composite questionnaire was administered at baseline and at 1, 4, 8, and 12 months. Long-term urinary complications were scored using a modified Radiation Therapy Oncology Group scale. RESULTS All 4 urinary subdomain scores evaluating acute urinary side effects after treatment (bother, function, incontinence, and irritation or obstruction) had returned to baseline levels by 8 months after implantation. At 5 years, the cumulative risks of late urinary complications by grade were 8.6% for grade 1 complications, 6.5% for grade 2, 1.7% for grade 3%, and 0.5% for grade 4. The most common grade 2 late urinary complications were urethral stricture (4 patients), incontinence requiring daily pads (3 patients), and intermittent hematuria (3 patients). Grade 3 complications were urinary retention requiring self-catheterization (2 patients) and severe frequency with dysuria (2 patients). The only grade 4 event was severe hemorrhagic cystitis. CONCLUSIONS Short-term urinary side effects after prostate brachytherapy are common, follow a predictable course, and typically resolve within 1 year. Conservative management of short-term urinary side effects is recommended to minimize the risk of long-term urinary complications.

An MRI-based dose–response analysis of urinary sphincter dose and urinary morbidity after brachytherapy for prostate cancer in a phase II prospective trial

PURPOSE To compare dose-volume histogram variables for the internal and external urinary sphincters (IUS/EUS) with urinary quality of life after prostate brachytherapy. METHODS AND MATERIALS Subjects were 42 consecutive men from a prospective study of brachytherapy as monotherapy with (125)I for intermediate-risk localized prostate cancer. No patient received hormonal therapy. Preplanning constraints included prostate V100 higher than 95%, V150 lower than 60%, and V200 lower than 20% and rectal R100 less than 1cm(3). Patients completed the Expanded Prostate Cancer Index Composite quality-of-life questionnaire before and at 1, 4, 8, and 12 months after implantation, and urinary domain scores were analyzed. All structures including the IUS and EUS were contoured on T2-weighted MRI at day 30, and doses received were calculated from identification of seeds on CT. Spearmans (nonparametric) rank correlation coefficient (ρ) was used for statistical analyses. RESULTS Overall urinary morbidity was worst at 1 month after the implant. Urinary function declined when the IUS V285 was 0.4% (ρ=-0.32, p=0.04); bother worsened when the IUS V35 was 99% (ρ=-0.31, p=0.05) or the EUS V240 was 63% (ρ=-0.31, p=0.05); irritation increased when the IUS V35 was 95% (ρ=-0.37, p=0.02) and the EUS V265 was 24% (ρ=-0.32, p=0.04); and urgency worsened when the IUS V35 was 99.5% (ρ=-0.38, p=0.02). Incontinence did not correlate with EUS or IUS dose. CONCLUSIONS Doses to the IUS and EUS on MRI/CT predicted worse urinary function, with greater bother, irritative symptoms, and urgency. Incorporating MRI-based dose-volume histogram analysis into the treatment planning process may reduce acute urinary morbidity after brachytherapy.

Improving prostate brachytherapy quality assurance with MRI–CT fusion–based sector analysis in a phase II prospective trial of men with intermediate-risk prostate cancer

PURPOSE We combined sector analysis with MRI-CT fusion to comprehensively assess postimplant dosimetry after prostate brachytherapy. METHODS AND MATERIALS Subjects were 50 men with intermediate-risk prostate cancer treated with (125)I brachytherapy in a prospective phase II clinical trial. On Day 30 after the implantation, dosimetry was evaluated in the prostate base, midgland, and apex regions on fused MRI-CT scans and CT scans. Volumes of each sector receiving 100% of the prescribed dose (V100) and doses to 90% of each sector (D90) were also calculated on the ultrasonogram used for treatment planning and compared with values derived from CT and fused MRI-CT scans. RESULTS Fused MRI-CT scans revealed lower-than-expected doses for the whole prostate (V100=91.3%, D90=152.9Gy) compared with CT scans (98.5% and 183.6Gy, p<0.0001) and lower doses to the prostate base (V100=79%, D90=130Gy) vs. CT (96% and 170Gy, p<0.0001). However, lower doses to the prostate base did not adversely affect biochemical outcomes in men with biopsy-proven disease at the base. At a median followup time of 42 months, the mean prostate-specific antigen level for all patients was 0.3ng/mL, and no patient had experienced biochemical or clinical progression or recurrence. CONCLUSIONS MRI-CT fusion-based sector analysis was feasible and revealed significantly lower doses to the prostate base than doses estimated from CT alone, although this did not affect biochemical outcomes. MRI-CT fusion-based sector analysis may be useful for developing MRI-based dosimetric markers to predict disease outcomes and treatment-related morbidity.

Is a Loose-Seed Nomogram Still Valid for Prostate Brachytherapy in a Stranded-Seed Era?

PURPOSE To characterize the amount of activity required to treat the prostate with stranded (125)I radioactive seeds and compare our stranded data with the amount of activity recommended when individual seeds are implanted using a Mick applicator. METHODS AND MATERIALS Data from two groups of patients at The University of Texas M. D. Anderson Cancer Center who were treated with prostate brachytherapy as monotherapy were analyzed. The first group included 100 patients implanted with individual seeds in 2000 and 2001. The second group comprised 81 patients for whom stranded seeds were implanted in 2006 and 2007. Seeds in both groups were (125)I seeds with an air kerma strength of 0.497 U per seed (0.391 mCi per seed). The prescribed dose to planning target volume was 145 Gy. RESULTS The total implanted activity and the number of seeds used were significantly lower in the second group (p < 0.0001) than in the first group. The reduction in activity in the stranded-seed group was approximately 23% for a 20-cm(3) prostate and approximately 15% for a 60-cm(3) prostate. With equivalent activity between the two groups, the stranded-seed treatment covered a larger treatment volume with the prescribed dose. CONCLUSIONS The amount of activity required to effectively treat a prostate of a given volume was lower with stranded seeds than with loose seeds. Our experience suggests that prostate brachytherapy that uses stranded seeds leads to a more efficient implant with fewer seeds and lower overall activity, resulting in improved homogeneity.

Sexual potency preservation and quality of life after prostate brachytherapy and low-dose tadalafil.

PURPOSE To prospectively determine sexual function, bother, and potency preservation in men treated with prostate brachytherapy and twice-weekly tadalafil. METHODS AND MATERIALS From 2005 to 2011, men treated with low-dose-rate prostate brachytherapy were treated on a prospective registration study. All patients were prescribed tadalafil 10mg twice weekly. The expanded prostate cancer index composite questionnaire was administered before treatment and at each followup. A subgroup analysis of men with sexual potency at baseline was performed. RESULTS A total of 237 men were analyzed. Median age was 64 years (range, 44-86). Median followup was 24.8 months (range, 1-60). At baseline, 175 men (74%) reported erections firm enough for sexual activity and 148 (62%) were potent (erections firm enough for intercourse). Statistically significant changes in sexual function/bother were appreciated from baseline throughout the analysis period, although absolute changes were relatively small and did not meet criteria for clinical significance. At 24-months followup, 72% reported erections firm enough for sexual activity and 56% were potent. Of men with potency at baseline, 89% had erections firm enough for sexual activity and 76% remained potent 24 months after treatment. CONCLUSIONS Peri-procedural tadalafil and prostate brachytherapy resulted in high rates of sexual potency preservation and no clinically significant effect on sexual quality of life.

Sexual function and the use of medical devices or drugs to optimize potency after prostate brachytherapy.

PURPOSE Prospective evaluation of sexual outcomes after prostate brachytherapy with iodine-125 seeds as monotherapy at a tertiary cancer care center. METHODS AND MATERIALS Subjects were 129 men with prostate cancer with I-125 seed implants (prescribed dose, 145 Gy) without supplemental hormonal or external beam radiation therapy. Sexual function, potency, and bother were prospectively assessed at baseline and at 1, 4, 8, and 12 months using validated quality-of-life self-assessment surveys. Postimplant dosimetry values, including dose to 10% of the penile bulb (D10), D20, D33, D50, D75, D90, and penile volume receiving 100% of the prescribed dose (V100) were calculated. RESULTS At baseline, 56% of patients recorded having optimal erections; at 1 year, 62% of patients with baseline erectile function maintained optimal potency, 58% of whom with medically prescribed sexual aids or drugs. Variables associated with pretreatment-to-posttreatment decline in potency were time after implant (p = 0.04) and age (p = 0.01). Decline in urinary function may have been related to decline in potency. At 1 year, 69% of potent patients younger than 70 years maintained optimal potency, whereas 31% of patients older than 70 maintained optimal potency (p = 0.02). Diabetes was related to a decline in potency (p = 0.05), but neither smoking nor hypertension were. For patients with optimal potency at baseline, mean sexual bother scores had declined significantly at 1 year (p < 0.01). Sexual potency, sexual function, and sexual bother scores failed to correlate with any dosimetric variable tested. CONCLUSIONS Erections firm enough for intercourse can be achieved at 1 year after treatment, but most men will require medical aids to optimize potency. Although younger men were better able to maintain erections firm enough for intercourse than older men, there was no correlation between potency, sexual function, or sexual bother and penile bulb dosimetry.

Prostogram Predicted Brachytherapy Outcomes are Not Universally Accurate: An Analysis Based on the M. D. Anderson Cancer Center Experience With 125Iodine Brachytherapy

PURPOSE Many clinicians use Prostogram data to advise patients selecting prostate cancer therapy. We examined whether the Prostogram accurately predicted recurrence at 5 years in patients treated with (125)I brachytherapy at 1 tertiary cancer center. MATERIALS AND METHODS We retrospectively reviewed the records of 208 consecutive patients with prostate cancer treated with a permanent (125)I implant without neoadjuvant androgen deprivation therapy at 1 tertiary cancer center during 1998 to 2006. In each patient the Prostogram brachytherapy formula was used to calculate 5-year biochemical recurrence-free survival probability based on clinical stage, Gleason sum score, prostate specific antigen and the receipt or not of external beam radiotherapy. Recurrence was defined as clinical relapse, death from disease, posttreatment androgen deprivation therapy, secondary treatments administered before prostate specific antigen failure or biochemical recurrence based on the Kattan modification of the American Society for Therapeutic Radiology and Oncology definition of biochemical recurrence after external beam radiation therapy. Patients were divided into quartiles based on Prostogram predicted 5-year recurrence-free survival probability and mean probability was compared to the actual 5-year recurrence-free survival rate in each quartile. Harrells concordance statistic was used to assess the predictive accuracy of the nomogram. RESULTS Actual 5-year biochemical recurrence-free survival rates were superior to Prostogram predicted probabilities, including 89% vs 80%, 87% vs 86%, 100% vs 89% and 100% vs 94% in quartiles 1 to 4, respectively. Harrells concordance value was 0.487 (95% CI 0.369-0.605), indicating that the predictive accuracy of the nomogram in our patients was less than 50%. CONCLUSIONS The Prostogram did not predict recurrence after permanent prostate brachytherapy in this series. Institutional variability requires that clinicians be cautious when using the Prostogram to counsel patients about the probability of success after permanent prostate brachytherapy.

MRI-based sector analysis enhances prostate palladium-103 brachytherapy quality assurance in a phase II prospective trial of men with intermediate-risk localized prostate cancer.

PURPOSE Palladium-103 ((103)Pd) may be superior to other isotopes in brachytherapy for localized intermediate-risk prostate cancer because of its relatively short half-life, higher initial dose rate, and greater dose heterogeneity within the target volume; these properties also underscore the need for accurate target delineation and postimplant quality assurance. We assessed the use of prostate sector analysis based on MRI for quality assurance after (103)Pd monotherapy. METHODS AND MATERIALS Fifty men with intermediate-risk prostate cancer underwent (103)Pd monotherapy in a prospective phase II trial at MD Anderson Cancer Center. Dosimetric analyses on day 30 after the implant were done using both CT and fused CT/MRI scans. Dosimetric variables were assessed for the entire prostate and for each of three or six sectors. Volumes and dosimetric variables were compared with paired t tests. RESULTS Postimplant dosimetric variables for the entire prostate were significantly different on CT vs. CT/MRI (p = 0.019 for V100 and p < 0.01 for D90). Prostate volumes were smaller on the CT/MRI scans (p < 0.00001). The base sector contributed the greatest difference, with doses based on CT/MRI lower than those based on CT (p < 0.01 for V100 and D90). To date, these lower base doses have not affected biochemical outcomes for patients with disease in prostate base biopsy samples. CONCLUSIONS CT/MRI is more precise than CT for prostate volume delineation and dosimetric quality assessment and thus provides superior heterogeneity control assessment after (103)Pd monotherapy implants.

Long-term tumor control after brachytherapy for base-of-prostate cancer.

Purpose To evaluate the outcomes of patients presenting with cancer at the base of the prostate after brachytherapy as monotherapy. Material and methods We retrospectively reviewed the medical records of all patients who had undergone transperineal ultrasound-guided implantation with 125I or 103Pd seeds as monotherapy between March 1998 and December 2006, at our institution. A minimum follow-up interval of 2 years was required for inclusion in our analysis. Dosimetry was assessed using computed tomography 30 days after the implant. Treatment failure was defined as the appearance of biopsy-proved tumor after seed implantation, radiographic evidence of metastases, receipt of salvage therapy, or elevation of the prostate-specific antigen level beyond the nadir value plus 2 ng/mL. Results With a median follow-up interval of 89 months (range 25–128 months), all 52 of the identified patients had no evidence of disease progression or biochemical failure. The mean number of cores sampled at the prostate base was 2.84 (median 2); Gleason scores assigned at central review were 6-8 in all patients. Of the 30 patients (58%) for whom dosimetric data were available at day 30, the median V100 values of the right and left base were 92.0% and 93.5%, respectively, and the median D90 values of the right and left base were 148 Gy and 151 Gy, respectively. Conclusion Permanent prostate brachytherapy as monotherapy results in a high probability of disease-free survival for men with cancer at the base of the prostate.