Biomedical subjects

N N Stone

Publications and source records attributed to N N Stone.

At least 37 records · Page 2Linked to original sources

PubMed2000

Prior transurethral resection does not increase morbidity following real-time ultrasound-guided prostate seed implantation.

PURPOSE: Patients with localized prostate cancer who had a prior open prostatectomy or transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH) may be at risk for greater morbidity when treated with brachytherapy. This analysis examines the morbidity following brachytherapy using the real-time method to determine if patients with a history of TURP are at increase risk for developing complications. MATERIALS AND METHODS: An ultrasound-guided transperineal interactive prostate seed was implanted in 419 patients with T1-T2 prostate cancer. All patients were implanted using a peripheral weighting of sources (75%) with the interior sources placed at least 5 mm from the urethra. The patients were divided into two groups: group 1 consisted of 376 patients (89.7%) without a prior TURP, and group 2 consisted of 43 patients (10.3%) who had a TURP prior to their implant. The mean age, prostate-specific antigen level, Gleason score, clinical stage, prostate volume, isotope implanted, and number of patients treated with neoadjuvant hormone therapy were comparable for both groups. RESULTS: Median follow-up for group 1 was 12 months and for group 2 was 18 months. No patients suffered from radiation-related proctitis or cystitis in either group of patients. Two patients in group 2 implanted with iodine 125 and who had a history of two prior TURPs developed mild superficial urethral necrosis (SUN). The actuarial freedom from developing superficial urethral necrosis at 4 years was 84% in patients with a history of prior TURP. There were no episodes of SUN in group 1 and no cases of incontinence reported in either group of patients. The actuarial rate of potency was 78% at 2 years. CONCLUSION: Whereas other techniques of seed implantation report incontinence in patients who had a prior open prostatectomy or TURP, the real-time method combined with peripheral loading avoids this complication.

Adult↗

PubMed2000

Use of radioimmunoscintigraphy with indium-111-labeled CYT-356 (ProstaScint) scan for evaluation of patients for salvage brachytherapy.

PURPOSE: Indium 111 capromab pendetide radioimmunoscintigraphy (ProstaScint) has been used to detect occult recurrent carcinoma after radical prostatectomy. MATERIALS AND METHODS: We evaluated the role of ProstaScint in 24 men with rising prostate-specific antigen (PSA) level following definitive radiation therapy to differentiate between local and distant recurrence in this patient population. RESULTS: ProstaScint scan detected prostatic uptake only in 16 patients, extraprostatic uptake in 5, both prostatic and extraprostatic uptake in 1, and no uptake in 2. Ten of 21 patients with prostatic uptake had positive biopsies, 5 had negative biopsies, and 6 were not biopsied. Two of the three patients with negative scans had positive biopsies, and the third patient was not biopsied. Three patients had evidence of osseous metastasis on radionuclide bone scan, two corresponding to the sites detected on ProstaScint. All three patients had abnormal uptake beyond the prostatic fossa with (n =2) or without (n = 1) prostatic uptake. There were no positive bone scans in patients without extraprostatic uptake on ProstaScint. CONCLUSIONS: ProstaScint scan is useful in detecting occult recurrence outside the prostate in patients with rising PSA following radiation therapy. Compared to data from radical prostatectomy, ProstaScint scans in these patients reveal a higher prevalence of abnormal uptake in the prostate and less frequent extraprostatic uptake.

Aged↗

PubMed2000

Effects of neoadjuvant hormonal therapy on prostate biopsy results after (125)I and (103)Pd seed implantation.

BACKGROUND: Androgen ablation may improve the efficacy of radiation therapy. PATIENTS AND METHODS: A total of 296 patients who had either (125)I (206; 70%) or (103)Pd (90; 30%) transperineal prostate brachytherapy (no external-beam radiation) had routine transrectal ultrasound-guided needle biopsy (minimum six cores) 2 years after treatment without regard to disease status. Neoadjuvant hormonal therapy (NHT: leuprolide acetate and flutamide) was used in 115 patients (39%) for 3 months prior to and 3 months after the implant. RESULTS: Of the 296 patients, 30 (10%) had positive prostate biopsies. Biopsies were positive in 4 of 115 (3.5%) v 26 of 181 (14%) of those who received or had not received NHT, respectively (P = 0.002). When patients were separated into low risk (PSA < or = 10 ng/mL, stage < or = T(2a), and Gleason score < or = 6) and high risk (all others), it was seen that low-risk patients did not benefit from NHT (3.8 v 7.7% positive biopsy rate; P = 0.5) whereas high-risk patients did (3.4% v 21.1%; P = 0.003). CONCLUSION: Prostate brachytherapy yields high negative biopsy rates (90%) 2 years after treatment. Neoadjuvant hormonal therapy can improve the local control rates (as determined by biopsy) in patients undergoing (125)I or (103)Pd seed implantation. These results are most significant for patients who present with PSA >10 ng/mL, stage > or = T(2b) diseases, or Gleason score > or = 7 (high-risk status).

Androgen Antagonists↗

PubMed1999

Does prostate brachytherapy treat the seminal vesicles? A dose-volume histogram analysis of seminal vesicles in patients undergoing combined PD-103 prostate implantation and external beam irradiation.

PURPOSE: Combined brachytherapy of the prostate and external beam irradiation (EBRT) of the prostate and seminal vesicles (SV) is becoming a popular treatment for high-risk prostate cancer. Dose-volume histogram (DVH) analysis of the SV in patients undergoing this treatment was performed to determine the dose distribution to the SV and the adequacy of this treatment in patients with potential SV involvement. METHODS AND MATERIALS: Twenty-five consecutive patients were treated with a Pd-103 implant of the prostate alone and 45 Gy of EBRT to the prostate and SV. Attempts were not made to implant the SV but seeds were routinely placed at the junction of the prostate and SV. All patients underwent CT-based postimplant dosimetric analysis 1 month after implantation. As part of this analysis, DVH were generated for the prostate and total SV volume (SVT). In addition, the SV was divided into 6-mm-thick volumes identified as SV1, SV2, SV3, SV4, and SV5 starting from the junction of the prostate and SV and extending distally. DVH were also generated for these structures. Delivered dose was defined as the D90 (dose delivered to 90% of the organ on DVH). RESULTS: The median volumes in cc of the prostate, SVT, SV1, SV2, SV3, SV4, and SV5 were 34.33, 9.75, 2.7, 3.48, 2.92, 3.18, and 1.96 respectively. The SVT contained from 0-9 seeds (median 2). There was little dose delivered to the SVT and SV volumes from the implanted prostate. The median D90 values for the prostate, SVT, SV1, SV2, SV3, SV4, and SV5 were 8615 cGy, 675 cGy, 3100 cGy, 1329 cGy, 553 cGy, 246 cGy, and 67 cGy, respectively. The dose delivered to the prostate covered small percentages of SV. The percents of SV volumes covered by the prostate D90 were 11, 35, 3.3, 0, 0, and 0 for SVT, SV1, SV2, SV3, SV4, and SV5, respectively. CONCLUSIONS: DVH analysis of the SV reveals that dose generated from an implanted prostate contributes little to the SV. Those patients at high risk for SV involvement may be undertreated with combined EBRT to prophylactic doses and prostate implantation.

Brachytherapy↗

PubMed1999

PSA kinetics following I-125 radioactive seed implantation in the treatment of T1-T2 prostate cancer.

Although there is renewed interest in prostate brachytherapy, little information is available on the effect of the procedure on prostate-specific antigen (PSA) changes over time. This study describes PSA kinetics after iodine-125 (I-125) transrectal ultrasound-guided transperineal implantation of the prostate. From February 1991-September 1997, 207 patients were treated with an I-125 prostate implant alone for T1-T2 prostate cancer. PSA values were obtained prior to treatment and at 1-73 months (median, 24 months). The change in PSA after implantation of the prostate was measured as a fraction of the pretreatment PSA (PSA at follow-up/pretreatment PSA). PSA failure was defined as two elevations in PSA or PSA > 1 ng/ml. One hundred fifty-five patients had PSA values recorded at the 1-month time period. A PSA value greater than the pretreatment PSA at 1 month was found in 27% (42/155). This had no significant effect on future PSA failure. The median percentage change in PSA after implantation for all patients were as follows: 1 month, 0.73; 3 months, 0.30; 6 months, 0.18; 12 months, 0.12; 18 months, 0.12; 24 months, 0.08; 30 months, 0.07; 36 months, 0.08; 42 months, 0.08; and 48 months, 0.05. The most significant decline occurred in the first 12 months. This was followed by a more gradual decline between 12-24 months. There was little change in PSA values after 24 months. The 1-year PSA value had a significant effect on PSA failure. Patients with a 1-year PSA <1 ng/ml (66) had an actuarial 4-year freedom-from-failure rate of 90%, compared to a rate of 62% for those with values >1 ng/ml (69) (P = 0.002). Twenty-seven patients developed PSA failure. The time to PSA failure ranged from 12-48 months (median, 24 months), but most (20/27) failures occurred after 18 months. We conclude that the greatest decline in PSA after I-125 implantation of the prostate occurs during the first year, and little change occurs after 2 years. A 1-year PSA value > 1 ng/ml is highly predictive of eventual PSA failure, which occurs in most patients after 18 months posttreatment.

Adenoma↗

PubMed1999

Prostate brachytherapy: treatment strategies.

PURPOSE: Patients who present with localized and locally advanced prostate cancer may be candidates for prostate brachytherapy. We evaluated the treatment outcomes in a diverse group of prostate cancer patients who presented with low, moderate and high risk features. MATERIALS AND METHODS: A total of 301 patients who presented with T1 to T3 prostate cancer were treated with brachytherapy alone or combined with hormonal therapy and/or external beam irradiation. Of these patients 109 at low risk with prostate specific antigen (PSA) 10 ng./ml. or less, Gleason score 6 or less and clinical stage T2a or less were treated with 125iodine alone, 152 at moderate risk with PSA greater than 10 ng./ml., Gleason score greater than 6 or stage T2b or greater were treated with 125iodine or 103palladium or combined implant alone with 5 months of hormonal therapy, and 40 at high risk with PSA greater than 15 ng./ml., Gleason 8 or greater, clinical stage T2c to T3 or positive seminal vesicle biopsy (20) were treated with combination brachytherapy, external beam irradiation and 9 months of hormonal therapy. Patients with a positive seminal vesicle biopsy (T3c disease) and negative pelvic lymph nodes were included in the high risk group, and the walls of the seminal vesicles were also treated with implantation. Followup was performed every 6 months with digital rectal examination and ultrasound evaluation. Prostate biopsy was routinely recommended 2 years after completion of the radiation. Failure was defined as PSA increase on 2 consecutive determinations above 1 ng./ml. or evidence of local recurrence on digital rectal examination, transrectal ultrasound or biopsy. Kaplan-Meier projections were used to calculate progression-free survival rates. RESULTS: Of the 109 patients at low risk followed from 1 to 7 years (median 18 months) 91% were free of PSA failure at 4 years. No patient experienced urinary incontinence following implantation, although grade 1 to 2 radiation proctitis occurred in 5 (4.5%). Of the 152 patients at moderate risk 73 received implantation and 79 received implantation combined with hormonal therapy. The 4-year biochemical freedom from failure rate for the hormone group was 85% versus 58% for the no hormone group (p = 0.08). The difference was more significant for those with Gleason score 7 or greater (90 versus 43%, p = 0.01) and for those with PSA greater than 10 ng./ml. (87 versus 59%, p = 0.04). Grade 1 to 2 radiation proctitis occurred in 1 of the 79 patients (1.3%) receiving hormonal therapy and in 3 (4%) treated with implantation only. There were no cases of urinary incontinence. Of the 40 patients at high risk 71% were free of biochemical failure at 3 years. Of the 4 patients with failure (10%) 3 (75%) originally had positive seminal vesicle biopsies. Five patients experienced gastrointestinal complications, although none was grade 3 or 4. The actuarial freedom from grade 2 proctitis was 82%. No patient experienced urinary incontinence. Prostate biopsies were negative in 87% of the low risk, 96.8 (hormone group) versus 68.6% (no hormone group) of the moderate risk (p = 0.0023) and 86% of the high risk patients. CONCLUSIONS: Brachytherapy appears to offer comparable results to external beam irradiation and radical prostatectomy when patients are stratified by disease extent. Adopting a strategy of implant alone, implant with hormonal therapy or implant with hormonal therapy and external beam irradiation in patients who present with low to high risk features can improve the overall results in the more advanced cases.

Brachytherapy↗

PubMed1999

Permanent radioactive seed implantation in the treatment of prostate cancer.

Prostate brachytherapy has come a long way in the last 15 years, from an open free-hand technique with which seed placement was often inaccurate to the highly technical and accurate procedure of today. It has become a viable treatment option for low-risk patients along with EBRT and prostatectomy. Its most promising use may be in combination with hormonal therapy and EBRT in moderate- to high-risk patients, for whom it may offer improved outcomes over standard single-modality therapies.

Brachytherapy↗

PubMed1999

Laparoscopic pelvic lymph node dissection in the staging of prostate cancer.

BACKGROUND: Men with localized prostate cancer who present with high risk features may benefit from determination of pelvic lymph node status by a laparoscopic lymph node dissection prior to definitive therapy. METHODS: One hundred eighty-nine men with a median age of 69 years (range 49-80) with T1-T3 prostate cancer had a laparoscopic pelvic lymph node dissection (LPLND) prior to definitive therapy (radiation or surgery). All patients had a negative bone scan and a computerized tomography of the pelvis prior to the LPLND. In addition, all patients also underwent a seminal vesicle biopsy (SVB) in order to determine the presence of T3c disease. Prostate-specific antigen (PSA) ranged from 1.6-190 ng/mL (median 11 ng/mL) and was > 10 ng/mL in 56.6%, Gleason score was > or = 7 in 46.7%, and 67.8% had clinical stage T2b-T3a. RESULTS: Of the 189 patients who underwent an LPLND, 22 (11.6%) had a positive dissection. Between 1 and 51 nodes (median 9) were removed per dissection. PSA, clinical stage, Gleason score and SVB results all significantly influenced node findings. Positive nodes were encountered in 26.5% of those with a PSA > 20 ng/mL (p = 0.0002), in 16.4% with stage T2b-T3a (p = 0.003), in 20% with Gleason scores 7-10 (p = 0.0006) and in 38% of men with a positive SVB (p < 0.0001). Logistic regression analysis with PSA, Gleason score, clinical stage and the results of the SVB demonstrated that a positive SVB was the most significant predictor of node positivity. The overall transfusion rate was 1% (2/189) and median hospital stay was one day. The complication rate for the LPLND was 9% (17/189). CONCLUSION: The LPLND is an effective and efficient means of detecting positive pelvic lymph nodes in patients with localized prostate cancer. It should be considered a necessary diagnostic modality in all appropriate patients who may be candidates for curative therapy.

Aged↗

PubMed1998

A dose-response study for I-125 prostate implants.

PURPOSE: No dose-response study has ever been performed for I-125 prostate implants using modern techniques of implant evaluation and modern treatment outcome end points. The amount of activity per volume implanted was increased over time based on review of postimplant dosimetry. This resulted in different delivered dose levels. This study explores the relationship between dose, biochemical failure, and biopsy results. MATERIALS AND METHODS: 134 patients with T1-T2 prostate cancer were implanted with I-125 radioactive seeds and followed from 12 to 74 months (median: 32) postimplant. No patient received external beam irradiation or hormonal therapy. All patients implanted with I-125 had Gleason scores < or =6. One month postimplant, a CT-based three-dimensional dosimetric evaluation was performed on all patients. Using TG43 guidelines, dose-volume histograms were calculated. The dose delivered to the gland was defined as the D90 (dose delivered to 90% of prostate tissue as defined by CT). The D90s ranged from 26.8 to 256.3 Gy (median: 140.8 Gy). Biochemical failure was defined as two consecutive rises in prostate specific antigen (PSA) or a nadir level above 1.0 ng/ml. Posttreatment prostate biopsies (six to eight core samples) were routinely performed at 2 years postimplant. RESULTS: Improvements in freedom from biochemical failure (FFBF) rates were seen with increasing D90 levels. The 4-year FFBF rates for patients with D90 values < 100 Gy, 100-119.9 Gy, 120-13.9 Gy, 140-159.9 Gy, and > or =160 Gy were 53, 82, 80, 95, and 89%, respectively (p = 0.02). Patients receiving a D90 < 140 Gy (65 patients) were similar with respect to presenting disease prognostic factors to those receiving a D90 > or =140 Gy (69 patients). Patients receiving a D90 < 140 Gy had a 4-year FFBF rate of 68% compared to a rate of 92% for those receiving a D90 > or =140 Gy (p = 0.02). Two-year posttreatment biopsies were negative in 70% (33 of 47) of patients with a D90 < 140 Gy compared to a rate of 83% (24 of 29) in patients with a D90 > or =140 Gy (p = 0.2). A multivariate analysis using dose, PSA, score, and stage revealed that dose was the most significant predictor of biochemical failure (p = 0.001). This dose response was more pronounced in patients presenting with PSA levels > 10 ng/ml. In these patients, the 4-year FFBF rates were 51 and 100% for the low and high dose groups, respectively (p = 0.009) and the negative biopsy rates were 64% (14 of 22) and 100% (8 of 8), respectively (p = 0.05). In patients with presenting PSA <10 ng/ml, the 4-year FFBF rates were 82 and 88% for the low and high dose groups, respectively (p = 0.29). CONCLUSION: A dose response was observed at a level of 140 Gy. Adequate I-125 implants should deliver a dose of 140-160 Gy using TG43 guidelines.

Brachytherapy↗

PubMed1998

Acute urinary morbidity following I-125 interstitial implantation of the prostate gland.

The objective of this paper was to evaluate the acute urinary morbidity associated with I-125 interstitial implantation of the prostate gland. From 1991-1995, 117 patients underwent ultrasound (U/S)-guided implantation of the prostate gland. Median dose to 90% of the gland (d90) was 14.68 Gy (range = 1.65-21.75 Gy). The patients' urinary symptoms were recorded pre-implantation and at regular intervals after implantation using the International Prostate Symptom Score (IPSS), a self-assessment questionnaire in which patients scored 7 symptoms: incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Median follow-up was 12 months. The natural history of implant-related urinary symptoms was assessed in this manner. In addition, dosimetric factors including U/S prostate volume, total activity, activity per seed, dose volume histogram (DVH) values for dose to gland, and dose area histogram (DAH) values for dose to urethra and bladder were examined for correlation to the severity of each symptom as well as to total IPSS (sum of the individual symptom scores). Total IPSS peaked at 1 month post-implant and gradually returned to approximately baseline at 24 months. Total IPSS directly correlated with total activity and DVH for the prostate. Total IPSS, however, did not correlate with bladder or urethral DAH. With the exception of frequency, individual symptoms did not correlate with dose to gland, bladder, or urethra. Frequency scores did, however, correlate not only with dose to prostate gland but also dose to urethra. The acute urinary side effects of I-125 prostate implantation are transient and peak at 1 month post-implant. The severity of the urinary irritative symptoms developed are closely related to total dose to the gland. Urethral dose appears to affect frequency most significantly. Urinary symptoms, therefore, may be a limiting factor when considering dose escalation with I-125.

Acute Disease↗

PubMed1998

Absence of 185delAG mutation of the BRCA1 gene and 6174delT mutation of the BRCA2 gene in Ashkenazi Jewish men with prostate cancer.

Epidemiological studies have demonstrated a clustering of breast and prostate cancers in some families. Moreover, there is an increase in the number of cases of prostate cancer in families with inherited mutations of the breast cancer susceptibility gene BRCA1. We assessed the role of BRCA1 and BRCA2 in prostate cancer. We tested for the BRCA1 185delAG frameshift mutation, found in 0.9% of Ashkenazi Jews, and the BRCA2 6174delT mutation, found in 1% of Ashkenazi Jews, in Ashkenazi Jewish men with prostate cancer. We studied 60 Ashkenazi men with prostate cancer. A family history was obtained by interview or a self-report questionnaire. Histological confirmation of diagnosis was obtained for all subjects. Ethnic background was confirmed for all subjects by self-report or interview. Mutations of BRCA1 and BRCA2 were detected by amplification of lymphocyte DNA from peripheral blood according to standard polymerase chain reaction (PCR) and dot blot procedures. Patients' ages ranged from 55 to 80 years (mean +/- s.d. 70 +/- 5.25). There were six men with a family history of prostate cancer; three of these had a father with prostate cancer. Five of the men had a family history of breast cancer, in a mother, a sister or an aunt. None of the men had a family history of both breast and prostate cancer. None of the 60 men carried the 185delAG BRCA1 or 6174delT BRCA2 mutations. Of 268 Ashkenazi Jewish women with sporadic breast cancer, tested in an unrelated study, 16 carried either the 185delAG mutation of BRCA1 or the 6174delT mutation of BRCA2. There was a significant difference in the incidence of the BRCA1 and BRCA2 mutations in the breast and prostate cancer cases (P = 0.05, two-tailed Fisher's exact test). The contribution of germline BRCA1 and BRCA2 mutations to prostate cancer incidence is probably small and could be limited to specific subgroups.

Aged↗

PubMed1998

Prevalence and natural history of urinary symptoms in a longitudinal national prostate cancer screening (community-based) study.

The AUA Symptom score (AUASS) was administered for three consecutive years to participants in a national prostate cancer screening study. Although the prevalence symptom free (AUSS=0) individuals was very low (<7%) in this cohort of 16 000 men, mean AUASS and proportion of men in the mild, moderate and severe categories are equivalent to community-based studies from around the world. Across all ages and races, AUASS drops after 12 months but returns to original levels at 24 months. No differences in AUASS were noted for race when adjusted for age. Age is most strongly correlated to the increase in AUASS and to the severity of urinary symptoms.

Journal Article↗

PubMed1998

Identification of patients at increased risk for prolonged urinary retention following radioactive seed implantation of the prostate.

PURPOSE: Urinary retention is a frequently reported complication following radioactive seed implantation of the prostate. If retention is refractory, a post-implant transurethral prostatic resection may ultimately be required to relieve obstruction, leading to an increased risk of urinary incontinence. In this series the incidence of prolonged urinary retention was determined, and the effect of pretreatment and treatment related factors was analyzed to identify high risk patients. MATERIALS AND METHODS: A total of 251 patients with organ confined prostate carcinoma underwent transperineal prostate seed implantation. Of the patients 114 were implanted with 103palladium (103Pd) and 137 with 125iodine seeds. Of the patients who were implanted with 103Pd 90 received 3 months of neoadjuvant hormonal therapy. All patients had International Prostate Symptom Scores (I-PSS) recorded before implantation to assess the degree of urinary symptoms. In the patients receiving neoadjuvant hormones prostate volumes and I-PSS were recorded before initiation of hormone treatment and 3 months later at the time of implant. RESULTS: Urinary retention developed in 14 patients requiring catheterization for more than 48 hours. Median time to onset was 1 day after implant. Of these patients 6 ultimately required transurethral prostatic resection to relieve urinary obstruction. No patient had urinary incontinence following implantation or transurethral prostatic resection. Multivariate analysis revealed that pretreatment I-PSS, and combined treatment with hormonal therapy and 103Pd predicted for the development of retention. Patients with I-PSS 20 or greater had a 29% risk, I-PSS 10 to 19, 11% risk and I-PSS less than 10, 2% risk of retention. Neither patient age, clinical stage, prostate specific antigen, Gleason score, use of 125I nor prostate volume was significant. A subgroup analysis of patients receiving hormonal therapy and 103Pd revealed that those with persistent urinary symptoms (I-PSS 10 or greater) following 3 months of hormonal therapy had the greatest risk of prolonged retention (37%). CONCLUSIONS: The overall risk of prolonged urinary retention following prostate implantation was low in our series. Using the I-PSS questionnaire, high risk patients can be identified before treatment. Patients with significant pretreatment urinary symptoms or persistent urinary symptoms following 3 months of hormonal therapy and then implantation with 103Pd have the greatest risk.

Aged↗

PubMed1998

Perineural invasion and seminal vesicle involvement predict pelvic lymph node metastasis in men with localized carcinoma of the prostate.

PURPOSE: We evaluate the contribution of perineural invasion and seminal vesicle biopsy results in predicting pelvic lymph node metastases in men with T1 or T2 adenocarcinoma of the prostate. MATERIALS AND METHODS: A total of 212 men with localized prostate cancer were evaluated for serum prostate specific antigen (PSA), clinical stage, Gleason score and the presence of perineural invasion. Each patient had undergone seminal vesicle biopsies and a laparoscopic pelvic lymph node dissection before definitive therapy. The pretreatment prognostic values, presence of perineural invasion and seminal vesicle involvement were compared to the results of the laparoscopic pelvic lymph node dissection. Differences in proportions were tested using the Pearson chi-square test. The effect of multiple variables was tested using a stepwise logistic regression analysis. RESULTS: PSA ranged from 1.6 to 190 ng./ml. (median 11), and 52% of patients had Gleason score 7 or greater and 67.5% had clinical stage T2b or greater disease. Of the 212 patients 37 (17.5%) had perineural invasion, 43 (20.3%) seminal vesicle involvement and 21 (10%) positive node dissections. A PSA greater than 20 ng./ml. (20 versus 6.8%, p = 0.006), Gleason score 7 or greater (15.5 versus 3.9%, p = 0.005), clinical stage T2b or greater (14 versus 0.6%, p = 0.004), presence of perineural invasion (27 versus 6%, p = 0.0001) and seminal vesicle involvement (32.6 versus 4.1%, p <0.0001) influenced nodal findings. However, in the logistic regression model only the positive seminal vesicle biopsy (p = 0.0006), presence of perineural invasion (p = 0.04) and PSA greater than 20 ng./ml. (p = 0.044) were significant variables. Of the 21 men with positive node dissections 18 (85.7%) had a positive seminal vesicle biopsy or perineural invasion. Separation of patients into a high risk group defined by a positive seminal vesicle biopsy or perineural invasion, or a low risk group defined as the absence of these features yielded a significant association with nodal involvement (28 versus 2%, p <0.0001). A separate analysis of the patients with a negative seminal vesicle biopsy demonstrated that only perineural invasion (19 versus 2%, p = 0.0002) and PSA greater than 20 ng./ml. (12 versus 2%, p = 0.01) conferred a greater risk of nodal metastases. A logistic regression analysis in the negative seminal vesicle biopsy group discarded all of the variables other than perineural invasion as significant. CONCLUSIONS: A positive seminal vesicle biopsy is the most significant predictor of pelvic lymph node metastases in men with T1 or T2 prostate cancer. Perineural invasion is also an independent predictor of nodal disease. Patients with either of these features should undergo pelvic lymph node dissection before receiving definitive therapy.

Adenocarcinoma↗

PubMed1998

Does pelvic irradiation play a role in the management of prostate cancer?

The optimal management of patients with lymph node-positive prostate cancer remains controversial. The role of pelvic irradiation in patients at high risk for nodal involvement continues to be debated. Studies of prostate irradiation with and without inclusion of the pelvic lymph nodes show poor outcomes for node-positive patients, supporting the concept that many of these patients have systemic disease at presentation. Although no randomized trial has examined the role of pelvic irradiation in pathologically node-positive patients, available data fail to reveal any significant benefit of this approach over prostate-alone irradiation. More promising therapeutic approaches involve the combination of local therapy and sustained hormonal therapy. Series comparing prophylactic irradiation of the pelvis and prostate to irradiation of the prostate alone have shown no clear benefit of pelvic irradiation. Pelvic irradiation may play a role in the treatment of early-stage or occult nodal disease, although this has yet to be examined. Until prospective, randomized trials demonstrate the efficacy of pelvic irradiation in the management of prostate cancer, its use cannot be routinely recommended. Data support the use of lymphadenectomy in high-risk patients to identify those with positive nodes, since these patients require androgen withdrawal therapy.

Clinical Trials as Topic↗

PubMed1997

Prospective analysis of prostate-specific markers in pelvic lymph nodes of patients with high-risk prostate cancer.

BACKGROUND: Pathologic evidence of pelvic lymph node involvement is obtained in 12%-20% of patients with localized prostate cancer that exhibits high-risk features (defined on the basis of tumor size, serum prostate-specific antigen [PSA] level, or Gleason score). The rate of systemic failure (i.e., relapse) in patients with this type of prostate cancer and no pathologic evidence of regional lymph node involvement is 55%-92% within 5 years of definitive local therapy. Since reverse transcription-polymerase chain reaction (RT-PCR) methods are likely to be more sensitive than routine pathologic examination in detecting metastatic tumor cells, we compared the ability of the two approaches to detect prostate cells in the pelvic lymph nodes of patients with localized, high-risk disease. METHODS: Fifty-eight lymph node specimens isolated from 33 patients before definitive local therapy were examined. Expression of PSA and prostate-specific membrane antigen (PSM) messenger RNAs in the specimens was assessed by means of nested RT-PCR. RESULTS: Pathologic examination identified tumor cells in the lymph nodes of four (12%) of the 33 patients, and PSA and/ or PSM expression was positive in specimens from 27 (82%) of the patients (two-sided P<.0001). The four patients with positive pathologic findings also had positive RT-PCR results. Among the 29 patients with no pathologic evidence of lymph node involvement, 23 (79%) tested positive by means of RT-PCR. In these 23 patients, PSM expression was detected more frequently than PSA expression; however, in two patients, only PSA expression was detected. CONCLUSIONS: Expression of prostate-specific markers in the pelvic lymph nodes of patients with localized, high-risk prostate cancer may indicate the presence of metastatic tumor cells. Such cells may be responsible for the high rate of systemic failure seen in these patients. Additional studies are required to determine the prognostic relevance of our findings.

Antigens, Neoplasm↗

PubMed1997

A new technique for performing Syed-Neblett template interstitial implants for gynecologic malignancies using transrectal-ultrasound guidance.

PURPOSE: Interstitial brachytherapy plays an important role in the treatment of advanced and recurrent gynecologic malignancies. Unfortunately, the inability to visualize the tumor and surrounding normal structures during the implant has hampered the accuracy and safety of the implant. Transrectal ultrasound guided Syed-Neblett template implantation is a new technique for performing interstitial implants under direct visualization. The details of the technique are presented to demonstrate the ability to accurately guide needle placement into tumor and avoid needle insertion into critical surrounding normal structures. METHODS AND MATERIALS: The transrectal ultrasound is positioned so that it can visualize the tumor, and normal surrounding structures in both transverse and longitudinal planes. The Syed-Neblett template is positioned and sutured into the perineum. Needles are inserted into the target area under direct visualization through transverse imaging. The bladder and rectum can be directly imaged and thus avoided. Longitudinal imaging is then used to guide the needles to the appropriate depth. In addition, it can be used to assess the length of the target volume and aid in determining the active length of the sources. RESULTS: A total of 12 procedures have been performed on seven patients from August 30, 1995 to April 12, 1996. The presenting diseases included: Stage IIIb cervical cancer in four cases, recurrent endometrial cancer in two cases, and Stage III vaginal cancer in one case. The total length of time for implantation of the needles ranged from 45 to 165 min (median--130 min). CONCLUSION: Transrectal ultrasound guidance provides real-time visualization of the target volume and normal tissues during interstitial implantation of gynecologic malignancies and allows for accurate needle placement.

Aged↗

PubMed1997

Laparoscopic pelvic lymph node dissection for prostate cancer: comparison of the extended and modified techniques.

PURPOSE: We compared the results of extended (obturator, hypogastric, common and external iliac nodes) to modified (obturator and hypogastric nodes only) laparoscopic pelvic lymph node dissection in patients with clinically localized prostate cancer. MATERIALS AND METHODS: A total of 189 patients with stage T1 to T3 prostate cancer underwent modified (150) or extended (39) laparoscopic pelvic lymph node dissection for pelvic nodal assessment before definitive treatment. RESULTS: Twice as many lymph nodes were removed via extended than modified laparoscopic pelvic lymph node dissection (mean 17:8 versus 9.3). The overall positivity rate was 23 of 189 lymph nodes (12.2%), including 14 of 150 (7.3%) for modified and 9 of 39 (23.1%) for extended dissection (p = 0.02). Two patients (22%) who underwent extended dissection had positive lymph nodes in the external iliac area. Patients who presented with the high risk features of prostate specific antigen (PSA) greater than 20 ng./ml., Gleason score 7 or greater, or stage T2b disease or greater had a 26.5% (p = 0.0002), 22% (p = 0.0006) or 16.4% (p = 0.003) likelihood of positive lymph nodes, respectively. For extended versus modified laparoscopic pelvic lymph node dissection node positivity in high risk patients was 27% versus 18.8% (p = 0.4), 30 versus 26.4% (p = 0.8) and 25.4 versus 14.6% (p = 0.17) for Gleason score 7 or greater, PSA greater than 20 ng./ml. and disease stage T2b to T3a, respectively. Patients who underwent the extended procedure had a higher complication rate (35.9 versus 2%, p < 0.0001). No laparotomy was required. CONCLUSIONS: Despite yielding a 2-fold higher node count and higher node positivity rate, extended laparoscopic pelvic lymph node dissection offers no advantage over modified laparoscopic pelvic lymph node dissection for diagnosing positive lymph nodes when results are analyzed by prognostic factors. The extended procedure is associated with a much higher complication rate. In patients with the high risk features of PSA greater than 20 ng./ml., Gleason score 7 or greater and stage T2b to T3a disease modified laparoscopic pelvic lymph node dissection can be performed safely and effectively to help identify those who may benefit most from curative therapy.

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