Cervical cancer screening decentralized policy adaptation: an African rural-context-specific systematic literature review.

BACKGROUND: Worldwide, nearly 570,000 women are diagnosed with cervical cancer each year, with 85% of new cases in low- and middle-income countries. The African continent is home to 35 of 40 countries with the highest cervical cancer mortality rates. In 2014, a partnership involving a rural region of Senegal, West Africa, was facing cervical cancer screening service sustainability barriers and began adapting regional-level policy to address implementation challenges. OBJECTIVE: This manuscript reports the findings of a systematic literature review describing the implementation of decentralized cervical cancer prevention services in Africa, relevant in context to the Senegal partnership. We report barriers and policy-relevant recommendations through Levesque's Patient-Centered Access to Healthcare Framework and discuss the impact of this information on the partnership's approach to shaping Senegal's regional cervical cancer screening policy. METHODS: The systematic review search strategy comprised two complementary sub-searches. We conducted an initial search identifying 4272 articles, then applied inclusion criteria, and ultimately 19 studies were included. Data abstraction focused on implementation barriers categorized with the Levesque framework and by policy relevance. RESULTS: Our findings identified specific demand-side (clients and community) and supply-side (health service-level) barriers to implementation of cervical cancer screening services. We identify the most commonly reported demand- and supply-side barriers and summarize salient policy recommendations discussed within the reviewed literature. CONCLUSIONS: Overall, there is a paucity of published literature regarding barriers to and best practices in implementation of cervical cancer screening services in rural Africa. Many articles in this literature review did describe findings with notable policy implications. The Senegal partnership has consulted this literature when faced with various similar barriers and has developed two principal initiatives to address contextual challenges. Other initiatives implementing cervical cancer visual screening services in decentralized areas may find this contextual reporting of a literature review helpful as a construct for identifying evidence for the purpose of guiding ongoing health service policy adaptation.

Uptake of Neonicotinoid Insecticides by Water-Foraging Honey Bees (Hymenoptera: Apidae) Through Guttation Fluid of Winter Oilseed Rape.

The water-foraging activity of honey bees (Apis mellifera L.) on guttation fluid of seed-coated crops, such as winter oilseed rape (WOR; Brassica napus L.), has not yet been evaluated. We analyzed the uptake of active substances (a.s.) in guttation fluid by evaluating residues of honey-sac contents. In autumn, insecticide residues of up to 130 µg a.s. per liter were released in WOR guttation fluid; this concentration is noticeably lower than levels reported in guttation fluid of seed-coated maize. Until winter dormancy, the concentrations declined to <30 µg a.s. per liter. In spring, residues were linked to prewintered plants and declined steadily until flowering. The maximum release of residues in guttation fluid of seed-coated WOR occurs on the first leaves in autumn when the colonies' water demand decreases. For the first time, proof for the uptake of guttation fluid from seed-coated WOR by honey bees was provided by measuring residues in individual honey-sac contents. In total, 38 out of 204 samples (19%) showed residues of thiamethoxam at concentrations ranging from 0.3 to 0.95 µg per liter while the corresponding concentrations in guttation fluid of WOR varied between 3.6 to 12.9 µg thiamethoxam per liter. The amounts of thiamethoxam we found in the honey sacs of water-foraging honey bees were therefore below the thresholds in nectar and pollen that are considered to have negative effects on honey bees after chronic exposure.

Performance of transperineal template-guided mapping biopsy in detecting prostate cancer in the initial and repeat biopsy setting.

Transrectal ultrasound (TRUS) biopsy can miss 20-30% of clinically significant cancers. We evaluate an alternative approach-transperineal template-guided mapping biopsy (TTMB) in the initial and repeat biopsy setting. From January 2005 through September 2008, 373 consecutive men underwent TTMB (294 men with > or =1 prior negative biopsy and 79 men as the initial biopsy). The location of each positive biopsy core, number of positive cores, and percent involvement of each core was recorded. Cancer detection rate for the initial biopsy was 75.9%. For men with 1, 2, and > or =3 prior negative biopsies detection rates were 55.5%, 41.7%, and 34.4%, respectively. In all, 55.5% of the cancers identified were Gleason > or =7. The majority of the cancers were multifocal. There was no significant change in the number of positive cores or Gleason score as the number of prior biopsies increased. The anterior and apical aspects of the prostate were among the most common cancer locations. TTMB provides a high rate of cancer detection as initial and repeat biopsy. TTMB was particularly effective at diagnosing anterior and apical cancer. TTMB may have particular application for men considering active surveillance, with prior negative TRUS biopsies, and those considering subtotal gland or other minimally invasive treatments.

Long-term urinary function after transperineal brachytherapy for patients with large prostate glands.

PURPOSE: To summarize longer-term postbrachytherapy morbidity in patients with prostate glands >50 cm3. METHODS AND MATERIALS: From 1997 to 1998, 33 patients with a transrectal ultrasound-based prostate volume >50 cm3 were treated at the University of Washington by 125I (144 Gy) or 103Pd (115 Gy) implantation for prostate carcinoma. These 33 patients comprised 7% of the total implant patient population. Twelve patients were treated with neoadjuvant androgen ablation before implantation. The (125)I source strength ranged from 0.34 to 0.5 mCi and the 103Pd source strength ranged from 1.1 to 1.4 mCi (pre-NIST-99). The total number of sources implanted was 94-223 (median 155). Despite the typical implant-related volume increase, the postimplant CT-defined prostate volumes were generally well-covered by the prescription isodose (median coverage 92%, range 80-100%). The preimplant urinary obstructive symptoms were quantified by the criteria of the American Urological Association. RESULTS: Of the 33 patients, 12 developed acute postimplant urinary retention, all presenting within 24 h of implantation. Patients who developed postimplant retention lasting >1 week were generally treated with intermittent self-catheterization. By 1 month, 85% of patients were catheter free. By 1 year, only 1 patient (4%) remained in urinary retention; the remainder of cases had resolved spontaneously. With follow-up of 1.7-2.6 years, the last American Urological Association scores were higher than the pretreatment scores in 15 patients and lower in 7 patients. No patient developed permanent urinary incontinence. Long-term changes in the American Urological Association scores were unrelated to whether the patient had been in urinary retention after implantation. Two patients developed rectal fistulas; they had preimplant transrectal ultrasound prostate volumes of 53 and 59 cm3, in the low range for this group of patients. No other patient had persistent rectal bleeding suggestive of clinically significant proctitis. The pretreatment serum prostate-specific antigen level was 3.3-15 ng/mL (median 7.2) and the last serum prostate-specific antigen level 0.1-1.6 ng/mL (median 0.2). CONCLUSION: Patients with larger prostate volumes appear to have moderate morbidity and a satisfactory technical outcome with brachytherapy. We do not believe the occurrence of two severe rectal complications was related to the prostate volume per se. Our experience and that of others calls into question the validity of using prostate volume as a criterion for patient suitability for prostate brachytherapy.

Dosimetric and radiographic correlates to prostate brachytherapy-related rectal complications.

Despite rates of radiation proctitis reported in the 1% to 9% range in most series, there is little information regarding rectal morbidity and dosimetric parameters. Accordingly, we have analyzed computed tomography (CT)-based dosimetric parameters based on a series of patients with endoscopically proven radiation proctitis. Nine patients diagnosed with radiation proctitis on endoscopy were identified in a prior review of 160 consecutively treated patients at the University of Washington in 1997. For each proctitis patient, two patients with no rectal bleeding matched for prostate size, isotope, and dose were selected as controls. Axial CT images obtained 2 to 4 hour postoperatively were used for postimplant dosimetry. Dose volume histograms of the rectum, surface area of the outer rectal wall receiving > or = 100% of the prescribed dose, maximum rectal dose, and length of rectum receiving > or = 100% prescription were obtained. Preimplant CT scans were used to group patients into three categories based on the amount of apparent rectal contact with the prostate. All rectal dosimetric parameters were statistically different between patients with or without rectal bleeding. The mean surface area receiving at least 100% prescription dose was 3.1 cm(2) for the controls vs. 6.9 cm(2) for the rectal bleeders (P = 0.001). The volume of rectum receiving at least 100% of prescription dose was 0.6 cc for the controls vs. 2.5 cc for the bleeders (P = 0.00008). Patients with full prostate-rectal contact had significantly higher rectal dose parameters compared to those with partial or no rectal contact. All nine proctitis patients were in the full-rectal-contact group compared to only seven of 18 (39%) controls. This detailed dosimetric analysis shows higher rectal doses for patients with radiation proctitis, making it a potential method of identifying patients at higher risk for receiving excessive rectal doses based on the anatomic relationship between the rectum and prostate on CT scan. Published 2001 Wiley-Liss, Inc.

Short-term sexual function after prostate brachytherapy.

Sexual function was evaluated in 34 patients with low-risk prostate cancer (PSA < or = 10, Gleason score < or = 6, clinical stage T1/T2) undergoing brachytherapy in a phase III prospective randomized trial comparing iodine-125 ((125)I) to palladium-103 ((103)Pd). The mean and median International Index of Erectile Function (IIEF) scores for the entire group were 14.2 and 16.5, respectively, and there was no difference between these scores when stratified by isotope. IIEF scores < 6, 6 to 11, and > or = 12 were recorded in 35% (12/34), 6% (2/34), and 59% (20/34) of patients, respectively. Hematospermia, orgasmalgia (pain at the time of orgasm), and alteration in intensity of orgasm were documented in 26% (9/34), 15% (5/34), and 38% (13/34) of patients, respectively, but these side effects were of limited duration for most patients. There was no relationship between radiation dose to the neurovascular bundles (NVB), which averaged 209% of the prescribed prostate dose, and the development of postbrachytherapy impotence. All four impotent patients who used sildenafil responded favorably. With a median follow-up of 13 months, 65% of patients undergoing prostate brachytherapy maintained sexual function without pharmacologic support. Including sildenafil responses, 76.5% of patients sustained erections sufficient for sexual intercourse.

Argon plasma coagulation for rectal bleeding after prostate brachytherapy.

PURPOSE: To better define the efficacy and safety of argon plasma coagulation (APC), specifically for brachytherapy-related proctitis, we reviewed the clinical course of 7 patients treated for persistent rectal bleeding. Approximately 2-10% of prostate cancer patients treated with 125I or 103Pd brachytherapy will develop radiation proctitis. The optimum treatment for patients with persistent bleeding is unclear from the paucity of available data. Prior reports lack specific dosimetric information, and patients with widely divergent forms of radiation were grouped together in the analyses. METHODS AND MATERIALS: Seven patients were treated with APC at the Veterans Affairs Puget Sound Health Care System and the University of Washington from 1997 to 1999 for persistent rectal bleeding due to prostate brachytherapy-related proctitis. Four patients received supplemental external beam radiation, delivered by a four-field technique. A single gastroenterologist at the Veterans Affairs Puget Sound Health Care System treated 6 of the 7 patients. If the degree of proctitis was limited, all sites of active bleeding were coagulated in symptomatic patients. An argon plasma coagulator electrosurgical system was used to administer treatments every 4-8 weeks as needed. The argon gas flow was set at 1.6 L/min, with an electrical power setting of 40-45 W. RESULTS: The rectal V100 (the total rectal volume, including the lumen, receiving the prescription dose or greater) for the 7 patients ranged from 0.13 to 4.61 cc. Rectal bleeding was first noticed 3-18 months after implantation. APC (range 1-3 sessions) was performed 9-22 months after implantation. Five patients had complete resolution of their bleeding, usually within days of completing APC. Two patients had only partial relief from bleeding, but declined additional APC therapy. No patient developed clinically evident progressive rectal wall abnormalities after APC, (post-APC follow-up range 4-13 months). CONCLUSIONS: Most patients benefited from APC, and no cases of clinically evident progressive tissue destruction were noted. Although APC appears to be efficacious and safe in the setting of the rectal doses described here, caution is in order when contemplating APC for brachytherapy patients.

Patient reported complications after prostate brachytherapy.

PURPOSE: Prostate brachytherapy has gained popularity due partly to the low rates of short-term complications shown in studies from highly select clinical practices. These series rely on medical records generated by the treating physician and are prone to underreport complications. We summarize the complication reports obtained directly from patients to establish a more realistic incidence of treatment related problems. MATERIALS AND METHODS: In 1997, 160 consecutive patients treated with prostate brachytherapy at the University of Washington were studied. A questionnaire was designed to determine the rate of complications occurring within 1 year of the procedure. The questions were formulated for ease of use and conciseness, while accounting for easily recalled events associated with complications. A total of 147 (92%) patients completed the questionnaire. RESULTS: There were 8 (5%) patients who required hospital admission for an average of 2 days (range 1 to 7) as a result of the procedure. A total of 56 (38%) patients required nonroutine visits with a physician in an office setting or at an emergency room. Radiation proctitis diagnosed by endoscopy developed in 8 (5%) patients but no one needed surgical intervention. A total of 47 (32%) patients required urinary catheterization at some point after implantation. CONCLUSIONS: We demonstrated a higher rate of short-term complications than those previously reported. Fortunately, the majority of side effects were self-limited and no treatment related mortality or cardiovascular morbidity was seen. Our findings may provide a more realistic account of the complications likely to occur after implantation than might be surmised from previous reports.

Temporary PSA rises and repeat prostate biopsies after brachytherapy.

PURPOSE: The long-standing confusion regarding the clinical relevance of postimplant biopsies is complicated by the common occurrence of temporary PSA rises between 1 and 2 years after brachytherapy. We report here 4 patients with temporary, self-limited PSA rises and postimplant biopsies, for whom radical prostatectomy was strongly advised but for whom surgery would probably have been the wrong choice. MATERIALS AND METHODS: Transperineal I-125 or Pd-103 implants were performed as previously described. After implantation, patients were followed routinely, with repeat PSA and physical examination at approximately every 4 to 6 months. Timing of postimplant PSAs was at the discretion of the patient and his doctors. Postimplant biopsies were performed in all cases out of concern for a persistently elevated serum PSA. Sections of fixed and embedded tissue were stained with standard hematoxylin and eosin. RESULTS: All 4 patients presented here were advised to have a salvage prostatectomy based primarily on their PSA changes. However, all of the patients have subsequently had a dramatic PSA fall, consistent with long-term cancer control, despite the fact that 3 of the 4 had histologic evidence of persistent cancer on repeat prostate biopsy. CONCLUSIONS: It is crucial that clinicians be aware of the potential for the doubly confusing situation of temporary PSA rises and apparently positive rebiopsies and the pressure it puts on both patients and their physicians to go ahead with inappropriate salvage therapy.

A comparison of radiation dose to the bulb of the penis in men with and without prostate brachytherapy-induced erectile dysfunction.

PURPOSE: To retrospectively evaluate the relationship between the radiation dose to the bulb of the penis and the development of erectile dysfunction (ED) in patients undergoing permanent prostate brachytherapy without external beam radiation therapy. METHODS AND MATERIALS: Twenty-three men who developed ED after transperineal ultrasound-guided permanent prostate brachytherapy for clinical T1/T2 adenocarcinoma of the prostate gland were paired with 23 similar men who maintained potency after implantation. Potency was defined as an erection sufficient for vaginal penetration. The mean and median follow-up for the entire group was 34.6 +/- 13.7 months and 32.8 months, respectively. Patients were implanted with either (125)I (145 Gy TG-43) or (103)Pd (115 Gy, pre-NIST-99). No patient received external beam radiation therapy either before or after brachytherapy. The bulb of the penis was outlined at 0.5-cm intervals on the Day 0 postimplant CT scan. The radiation dose distribution to the bulb of the penis was defined in terms of the minimal dose delivered to 25%, 50%, 70%, 75%, 90%, and 95% of the bulb (D(25), D(50), D(70), D(75), D(90), and D(95)). RESULTS: The radiation dose delivered to the bulb of the penis in men with postbrachytherapy-induced ED was statistically greater for all evaluated dosimetric parameters (D(25), D(50), D(70), D(75), D(90), and D(95)). Multivariate analysis indicated that dose to the bulb of the penis and patient age at the time of implant were predictive of postimplant ED, whereas choice of isotope had no effect. Among potent patients, 19/23 had D(50) < or = 40% of prescribed minimal peripheral dose, whereas for the impotent patients, 19/23 had D(50) >40% of the minimal peripheral dose. Of the impotent patients, 17 utilized sildenafil, with 15 experiencing a favorable response (88%). CONCLUSION: Our data suggest that prostate brachytherapy-induced impotence is highly correlated with the radiation dose delivered to the bulb of the penis. With Day 0 dosimetric evaluation, the radiation dose delivered to 50% of the bulb of the penis should be maintained at 50 Gy or less to maximize post-treatment potency. Fortunately, the majority of the brachytherapy-induced ED population responds favorably to sildenafil.

Improved outcomes with radiation for prostate cancer.

During the last 15 years, a series of substantial technical improvements have occurred in external beam radiation and brachytherapy. The introduction of PSA-based posttreatment monitoring has allowed a reasonable comparison between each radiation modality and prostatectomy. Such comparisons show more similarities than differences. Probably the most exciting finding in regard to curing cancer is that higher-risk patients have a more favorable prognosis than previously recognized using higher doses now achievable with either form of radiation.

Standardization of prostate brachytherapy treatment plans.

PURPOSE: Whereas custom-designed plans are the norm for prostate brachytherapy, the relationship between linear prostate dimensions and volume calls into question the routine need for customized treatment planning. With the goal of streamlining the treatment-planning process, we have compared the treatment margins (TMs) achieved with one standard plan applied to patients with a wide range of prostate volumes. METHODS AND MATERIALS: Preimplant transrectal ultrasound (TRUS) images of 50 unselected University of Washington patients with T1-T2 cancer and a prostate volume between 20 cc and 50 cc were studied. Patients were arbitrarily grouped into categories of 20-30 cc, 30-40 cc, and 40-50 cc. A standard 19-needle plan was devised for patients in the 30- to 40-cc range, using an arbitrary minimum margin of 5 mm around the gross tumor volume (GTV), making use of inverse planning technology to achieve 100% coverage of the target volume with accentuation of dose at the periphery and sparing of the central region. The idealized plan was applied to each patient's TRUS study. The distances (TMs) between the prostatic edge (GTV) and treated volume (TV) were determined perpendicular to the prostatic margin. RESULTS: Averaged over the entire patient group, the ratio of thickness to width was 1.4, whereas the ratio of length to width was 1.3. These values were fairly constant over the range of volumes, emphasizing that the prostate retains its general shape as volume increases. The idealized standard plan was overlaid on the ultrasound images of the 17 patients in the 30- to 40-cc group and the V100, the percentage of target volume receiving 100% or more of the prescription dose, was 98% or greater for 15 of the 17 patients. The lateral and posterior TMs fell within a narrow range, most being within 2 mm of the idealized 5-mm TM. To estimate whether a 10-cc volume-interval stratification was reasonable, the standard plan generated from the 30- to 40-cc prostate model was applied to 5 patients each from the 20- to 30-cc group and the 40- to 50-cc group. Using the standard plan designed for the 30- to 40-cc group, the TMs were closer to 10 mm than to 5 mm for the smaller volume glands and too small for the larger volume ones, assuming an ideal margin of 5 mm. CONCLUSION: The application of standardized plans to prostate brachytherapy is feasible. Stratifying the volume in 10-cc intervals appears to be adequate, suggesting that the majority of cases appropriate for treatment with brachytherapy might be treated with three standard plans. While the authors believe that the use of a limited number of standard treatment plans is feasible, practical, and medically acceptable, it should be emphasized that the use of a standard plan should always be previewed by computer-aided application to the particular patient's planning images.

Adventitial remodeling after angioplasty is associated with expression of tenascin mRNA by adventitial myofibroblasts.

OBJECTIVES: The purpose of this study was to determine the temporospatial expression of tenascin-C (TnC) in balloon-injured rat and porcine arteries. BACKGROUND: Recent studies suggest that cell migration, in addition to cell proliferation, is a critical component of neointima formation after vascular injury. We have previously shown that adventitial myofibroblasts synthesize growth factors that contribute to the formation of neointima after arterial injury. We have also shown that the extracellular matrix protein, TnC, regulates cell migration. Consequently, we investigated the temporospatial expression of TnC by myofibroblasts after vascular injury. METHODS: In situ hybridization and immunohistochemistry were used to investigate the temporospatial expression of TnC in injured arteries. Northern and Western blots were used to determine the in vitro expression of TnC. RESULTS: In situ hybridization revealed that the major site of TnC expression early after vascular injury was the adventitial myofibroblasts. Immunohistochemical staining demonstrated that TnC expression began in adventitial myofibroblasts three days after injury. Tenascin-C expression, however, did not persist in this region. Rather, it moved progressively across the vascular wall toward the luminal surface. By one week, TnC expression reached the developing neointima. In vitro, myofibroblasts did not express TnC mRNA under basal conditions. In contrast, angiotensin II and PDGF-BB, factors that have been implicated in remodeling of balloon-injured arteries, markedly upregulated TnC mRNA. CONCLUSIONS: Tenascin-C is expressed in response to balloon injury. Tenascin-C expression begins with adventitial myofibroblasts. Over a period of 7 to 14 days, expression moves progressively across the vessel wall to the neointima. We hypothesize that adventitial myofibroblasts are actively involved in the formation of neointima and that TnC facilitates migration of these cells during adventitial remodeling.

Preexisting histologic evidence of prostatitis is unrelated to postimplant urinary morbidity.

The presence and extent of prostatitis on the patients' preimplant biopsy slides was correlated with their postimplant course to determine if any relationship exists between histological prostatitis and postimplant morbidity. Biopsy slides from 56 patients treated with I-125 (144 Gy, TG-43), Pd-103 (125 Gy, NIST-1999), or Pd-103 plus supplemental external beam radiation (20-44 Gy) were studied. As part of ongoing prospective protocols, treatment-related morbidity is monitored by mailed questionnaires at 1, 3, 6, 12, and 24 months postimplant, using standard American Urologic Association (I-PSS) and Radiation Therapy Oncology Group criteria. Patient's preimplant biopsies, stained with standard hematoxylin and eosin, were retrieved for review by one uropathologist (LT). Separate evaluations of the degree and extent of inflammation in biopsy cores free of cancer and in cancerous biopsy cores were undertaken. Infiltrates were classified as periglandular if they were within 50 microns of a glandular structure. They were otherwise classified as stromal. Distribution of the inflammation was reported as focal, multifocal, or diffuse. The intensity of inflammation was separately graded as mild if there were fewer than 10 inflammatory cells per high-power field, moderate if there were 10-200 cells per high-power microscopic field, or severe if there were more than 200 cells per field. In all cases the great majority of inflammatory cells were mononuclear, predominantly lymphocytes. Periglandular inflammation was most common, with 18% of patients having focal periglandular and 20% having multifocal periglandular inflammation on their preimplant biopsies. Cancer-related infiltrates were the second most common, with 23% of patients having focal, 13% multifocal, and 13% diffuse cancer-related inflammation on their preimplant biopsies. Eight of the 55 patients developed postimplant urinary retention, requiring catheterization for 2 to 8 days. The overall incidence of postimplant urinary retention was low and there was no obvious relationship between the presence of inflammation on preimplant biopsy and the likelihood of postimplant urinary retention. AUA score changes at 1 and 6 months postimplant were highly variable and unrelated to the presence or severity of periglandular or cancer-related inflammation. Considering the apparent lack of relationship between histological findings and clinical outcomes in the patients reported here, the authors conclude that histologic evidence of prostatitis is not a contraindication to brachytherapy.

Follow-up care for cancer: making the benefits equal the cost.

Posttreatment follow-up is a staple of oncologic practice. Clinicians have traditionally presumed that close surveillance improves clinical outcome. However, new evidence reveals that frequent, procedure-intensive follow-up may provide no more significant benefit to patients than simpler approaches. Several recent consensus recommendations from major oncology organizations support this theory. Published surveys of clinician and institutional follow-up policies reveal significant variations in practice, with many providers continuing to use costly, unproven regimens. This review highlights current data on follow-up care for three common cancers--breast, colorectal, and prostate. These data suggest an acute need for changes leading to more rational, consistent, and efficient follow-up practices.

Transperineal brachytherapy in patients with large prostate glands.

The purpose of this study is to help clarify the use of prostate size as a selection factor for prostate brachytherapy. From 1997 to 1998, 33 patients with a TRUS-based prostate volume greater than 50 cc were treated at the University of Washington by I-125 (144 Gy) or Pd-103 (115 Gy) implantation for prostatic carcinoma. These 33 patients comprised 7% of the total implants performed. Each patient underwent a preimplant TRUS study in the lithotomy position, taking serial axial images of the prostate at 0.5 cm intervals from the base of the gland to the apex. The contours on the preimplant TRUS images were used to calculate the prostate volumes reported here. Only one patient received supplemental external beam irradiation prior to implantation. Twelve patients were treated with neoadjuvant androgen ablation prior to implantation. The prostate volumes quoted here are those taken after hormonal downsizing. Postimplant axial CT images were digitized to calculate the CT-based target coverage. Preimplant urinary obstructive symptoms were quantified by the criteria of the American Urologic Association. Each patient was contacted at the time of this article preparation to update postimplant morbidity information. In all cases, at least 80% of the postimplant volume was covered, despite a median implant-related volume increase of 15%. Five of the 33 patients' postimplant CT scans showed some degree of incomplete target coverage of the anterior/lateral prostate margin. There was no clear association between inadequate anterior/lateral coverage and the degree of interference. Twelve of the 33 patients developed acute postimplant urinary retention, all occurring within 24 hr of implantation. Within this group of 33 patients with a large prostate volume, there was no relationship between the likelihood of acute or chronic urinary retention and preimplant prostate size or obstructive symptoms. Patients who developed postimplant retention lasting more than one week were generally managed by intermittent self-catheterization. By one month, 85% of patients were catheter-free. Based on the data reported here, we are more inclined to accept patients with a large prostate for implantation without insisting on preimplant size reduction. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 199-205 (2000).

Prostate brachytherapy in patients with median lobe hyperplasia.

Our aim was to document the technical and clinical course of prostate brachytherapy patients with radiographic evidence of median lobe hyperplasia (MLH). Eight patients with MLH were identified during our routine brachytherapy practice, representing 9% of the 87 brachytherapy patients treated during a 6-month period. No effort was made to avoid brachytherapy in patients noted to have MLH on diagnostic work-up. Cystoscopic evaluation was not routinely performed. Postimplant axial computed tomographic (CT) images of the prostate were obtained at 0.5 cm intervals. Preimplant urinary obstructive symptoms were quantified by the criteria of the American Urologic Association (AUA). Each patient was contacted during the writing of this report to update postimplant morbidity information. There was no apparent association between the degree of MLH and preimplant prostate volume or AUA score. Intraoperatively, we were able to visualize MLH by transrectal ultrasound and did not notice any particular difficulty placing sources in the MLH tissue or migration of sources out of the tissue. The prescription isodose covered from 81% to 99% of the postimplant CT-defined target volume, achieving adequate dose to the median lobe tissue in all patients. Two of the eight patients developed acute, postimplant urinary retention. The first patient required intermittent self-catheterization for 3 months and then resumed spontaneous urination. MLH does not appear to be a strong contraindication to prostate brachytherapy, and prophylactic resection of hypertrophic tissue in such patients is probably not warranted. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 152-156 (2000).

Five-year biochemical outcome and toxicity with transperineal CT-planned permanent I-125 prostate implantation for patients with localized prostate cancer.

PURPOSE: To report the 5-year prostate-specific antigen (PSA) relapse-free survival outcome and incidence of long-term morbidity for patients with localized prostate cancer treated with CT-planned permanent I-125 prostate implantation using a transperineal technique (TPI). METHODS AND MATERIALS: Between 1989-1996, 248 patients with clinically localized prostate cancer were treated with TPI. The median age was 65 years (range: 45-80 years). The clinical stage was T1c in 143 patients (58%), Stage T2a in 102 (41%), and T2b in 3 (1%). Thirty patients (12%) had Gleason scores <6, 158 patients (64%) had Gleason scores of 6, and 60 (24%) had scores >or =7. The median pretreatment PSA was 7 ng/mL (range: 1-58 ng/mL). The median prescribed implant dose was 150 Gy. Patients were characterized as having favorable risk disease if their pretreatment PSA level was < or =10.0 ng/mL and Gleason score < or = 6; those with one and two adverse prognostic features (PSA > 10 ng/mL and Gleason score >6) were classified as having intermediate and unfavorable risk disease, respectively. PSA relapse was defined according to the American Society of Therapeutic Radiation Oncology Consensus Statement, and toxicity was scored according to the Radiation Therapy Oncology Group morbidity scoring scale. The median follow-up was 48 months (range: 12-126 months). RESULTS: Thirty-eight patients (15%) developed a PSA relapse, and the overall 5-year PSA relapse-free survival (PRFS) rate was 71%. The 5-year PRFS rates for favorable-risk (n = 146), intermediate-risk (n = 85), and unfavorable-risk (n = 17) patients were 88%, 77%, and 38%, respectively (p < 0.0001). The 5-year PRFS rates among patients treated with a 2-month course of neoadjuvant androgen deprivation (NAAD) prior to TPI compared to patients treated with TPI only were 100% and 77%, respectively (p = 0.03). Multivariate analysis identified pretreatment PSA > 10 ng/mL and Gleason score >6 as independent predictors for biochemical relapse after TPI. The 5-year actuarial likelihood of late Grade 2 urinary toxicity was 41%. The 5-year likelihood of urethral stricture development was 10%, and the median time to stricture development was 18 months. One patient (0. 4%) in the early phase of this clinical experience developed a Grade 4 urethral complication. The actuarial incidence of late Grade 2 rectal bleeding was 9%. One patient (0.4%) developed a Grade 4 rectal complication. CONCLUSIONS: Especially for favorable risk disease, the 5-year biochemical outcome with this approach was excellent and appears to be comparable to other therapeutic interventions. Grade 2 urinary symptoms were common in these patients but gradually resolved in most. Improved treatment planning approaches that further constrain the urethral dose without compromising the target volume dose will likely decrease the incidence of Grade 2 and 3 urinary symptoms after TPI.

Treatment margins for prostate brachytherapy.

The purpose of this article was to determine what planned treatment margin (TM) would allow for implant-related prostate volume changes and still achieve an adequate periprostatic cancercidal dose. Twenty consecutive, unselected patients who underwent (125)I implantation (144 Gy prescription dose) were studied. The treated volume (TV) was calculated as the volume encompassed by the 144 Gy isodose distribution. A post-implant computed tomography scan was obtained the following day, using 5-mm images at every 5 mm. The distances between the prostate margin (GTV) and TV were determined by measuring the distance between the ultrasound-defined prostatic margin and the prescription isodose, perpendicular to the prostatic margin. The lateral, anterior, and posterior TM margins were determined at the base, mid-level, and apex of the prostate. The pre-implant TV was nearly twice as large as the GTV, ranging from 36 to 199 mL (median, 73 mL). The anterior, lateral, and posterior planned TMs varied substantially between patients, due to lack of a consistent policy the magnitude of the CTV and the acceptable CTV-to-TV distance. For all measurement points, the median planned treatment margin was 3 mm (range, -16 mm to 14 mm). Overall, there was only a loose correlation between pre- and post-implant treatment margins primarily due to variable, implant-related prostatic dimensional changes. Patients with a greater implant-related volume increase tended to have smaller post-implant treatment margins. The post-implant TMs were negatively correlated with dimensional changes, and the negative correlation was most marked for the anterior and posterior TMs due to predominant anterior-posterior dimensional increase. As expected, the post-implant target coverage was higher when larger planning TMs were used, but the correlation was loose due to the unpredictable, highly variable degree of implant-related volume increase. We currently are using 5-mm TMs around the GTV, as identified on pre-implant transrectal ultrasonography or computed tomography. However, the poor correlation between planned and actual post-implant TMs call into question any attempt to make a rational recommendation regarding optimal TMs.