Select men benefit from androgen deprivation therapy delivered with salvage radiation therapy after prostatectomy.

BACKGROUND: Which men benefit most from adding androgen deprivation therapy (ADT) to salvage radiation therapy (SRT) after prostatectomy has not clearly been defined; therefore, we evaluated the impact of ADT to SRT on failure-free survival (FFS) in men with a rising or persistent PSA after prostatectomy. METHODS: We identified 332 men who received SRT after prostatectomy from 1987 to 2010. Recursive partitioning analysis (RPA) identified favorable, intermediate and unfavorable groups based on the risk of failure after SRT alone. Kaplan-Meier and log-rank tests compared FFS with and without ADT. RESULTS: Forty-three percent received SRT alone and 57% received SRT with ADT (median 6.6 months (interquartile range (IQR) 5.8-18.1) ADT). Median SRT dose was 70 Gy (IQR 70-70), and median follow-up after SRT was 6.7 years (IQR 4.5-10.8). On Cox's proportional hazard regression, ADT improved FFS (adjusted hazard ratio 0.60, 95% confidence interval: 0.42-0.86; P=0.006). RPA classified unfavorable disease as negative surgical margins (SMs) and preradiation PSA of ⩾0.5 ng ml-1. Favorable disease had neither adverse factor, and intermediate disease had one adverse factor. The addition of ADT to SRT improved 5-year FFS for men with unfavorable disease (70.3% vs 23.4%; P<0.001) and intermediate disease (69.8% vs 48.0%; P=0.003), but not for men with favorable disease (81.2% vs 78.0%; P=0.971). CONCLUSIONS: The addition of ADT to SRT appears to improve FFS for men with a preradiation PSA of ⩾0.5 ng ml-1 or with negative SM at prostatectomy. Men with involved surgical margins and PSA <0.5 ng ml-1 appear to be at a lower risk of failure after SRT alone and may not derive as much benefit from the administration of ADT with SRT. These results are hypothesis-generating only, and further prospective data are required to see if ADT can safely be omitted in this select group of men.

Factors associated with improved biochemical response to neoadjuvant androgen deprivation therapy before definitive radiation therapy in prostate cancer patients.

BACKGROUND: In prostate cancer patients treated with androgen deprivation therapy (ADT) and radiation therapy (RT), a pre-RT PSA level 0.5 ng ml(-1), determined after neoadjuvant ADT and before RT, predicts for worse survival measures. The present study sought to identify patient, tumor and treatment characteristics associated with the pre-RT PSA in prostate cancer patients. METHODS: We reviewed the charts of all patients diagnosed with intermediate- and high-risk prostate cancer and treated with a combination of neoadjuvant (median, 2.2 and 2.5 months, respectively), concurrent, and adjuvant ADT and RT between 1990 and 2011. RESULTS: A total of 170 intermediate- and 283 high-risk patients met inclusion criteria. On multivariate analysis, both intermediate- and high-risk patients with higher pre-treatment PSA (iPSA) were significantly less likely to achieve a pre-RT PSA <0.5 ng ml(-1) (iPSA 10.1-20 ng ml(-1): P=0.005 for intermediate risk; iPSA 10.1-20 ng ml(-1): P=0.005, iPSA >20 ng ml(-1): P<0.001 for high risk). High-risk patients undergoing total androgen blockade were more likely to achieve a pre-RT PSA <0.5 ng ml(-1) (P=0.031). We observed an interaction between race and type of neoadjuvant ADT (P=0.074); whereas African-American men on total androgen blockade reached pre-RT PSA <0.5 ng ml(-1) as frequently as other men on total androgen blockade (P=0.999), African-American men on luteinizing hormone-releasing hormone (LH-RH) agonist monotherapy/orchiectomy were significantly less likely to reach pre-RT PSA <0.5 ng ml(-1) compared with other men on LH-RH monotherapy/orchiectomy (P=0.001). CONCLUSIONS: Our findings suggest that total androgen blockade in the neoadjuvant period may be beneficial compared with LH-RH monotherapy for achieving a pre-RT PSA <0.5 ng ml(-1) in African-American men with high-risk prostate cancer. In addition, men with higher iPSA are more likely to have a pre-RT PSA greater than 0.5 ng ml(-1) in response to neoadjuvant ADT and are therefore candidates for clinical trials testing newer, more aggressive hormone-ablative therapies.

Addition of short-term androgen deprivation therapy to dose-escalated radiation therapy improves failure-free survival for select men with intermediate-risk prostate cancer.

BACKGROUND: Dose-escalated (DE) radiation therapy (RT) and androgen deprivation therapy (ADT) improve prostate cancer outcomes over standard-dose RT. The benefit of adding ADT to DE-RT for men with intermediate-risk prostate cancer (IR-PrCa) is uncertain. PATIENTS AND METHODS: We identified 636 men treated for IR-PrCa with DE-RT (>75Gy). The adult comorbidity evaluation-27 index classifed comorbidity. Kaplan-Meier and log-rank tests compared failure-free survival (FFS) with and without ADT. RESULTS: Forty-five percent received DE-RT and 55% DE-RT with ADT (median 6 months). On Cox proportional hazard regression that adjusted for comorbidity and tumor characteristics, ADT improved FFS (adjusted hazard ratio 0.36; P = 0.004). Recursive partitioning analysis of men without ADT classified Gleason 4 + 3 = 7 or ≥50% positive cores as unfavorable disease. The addition of ADT to DE-RT improved 5-year FFS for men with unfavorable disease (81.6% versus 92.9%; P = 0.009) but did not improve FFS for men with favorable disease (96.3% versus 97.4%; P = 0.874). When stratified by comorbidity, ADT improved FFS for men with unfavorable disease and no or mild comorbidity (P = 0.006) but did not improve FFS for men with unfavorable disease and moderate or severe comorbidity (P = 0.380). CONCLUSION: The addition of ADT to DE-RT improves FFS for men with unfavorable IR-PrCa, especially those with no or minimal comorbidity.

Dual radiobiological interpretations of retrospective clinical data: the time factor.

Dual interpretations are different radiobiological mechanisms that explain theoretically the same observed results. Radiobiological interpretations of the time factor are most frequently based on changes in total dose that produce a given effect. If this dose is increased by different mechanisms (e.g. increasing overall time and decreasing dose per fraction) at the same time, proposals for altered fractionation schemes based on the choice of one or the other mechanism, in principle, can lead to erroneous predictions of outcome. This is especially the case when the analyses are based on retrospective clinical data, where the influence of patient selection is unknown. Examples of dual interpretations taken from the literature on head and neck, melanoma and prostate cancer are discussed.

Adjuvant and salvage radiotherapy after radical prostatectomy for prostate cancer.

PURPOSE: The optimal role of radiotherapy (RT) to the prostate bed after radical prostatectomy (RP) is the subject of much debate. In this study, the results of adjuvant RT (ART) and salvage RT (SRT) were compared. METHODS AND MATERIALS: A total of 146 lymph node-negative patients were treated postoperatively after RP with RT to the prostate bed between 1987 and 1998. Of these, 75 patients had an undetectable prostate-specific antigen (PSA) level and were treated with ART for adverse pathologic features only to a median dose of 60 Gy (range 51-70). A positive margin was identified in 96%, and two of the three with negative margins had seminal vesicle involvement (SVI). SRT was administered for either a persistently detectable PSA level after RP (n = 27) or for a delayed rise in PSA (n = 44) to a median dose of 70 Gy (range 60-78). Adjuvant androgen ablation was given to 37 patients; 2 who had received ART and 35 had who received SRT. The median duration of androgen ablation was 24 months. The primary end point was freedom from biochemical failure (bNED), which was considered to be an undetectable PSA level. The median follow-up was 53 months for all patients: 68 months for the ART patients and 35 months for the SRT patients. RESULTS: For the ART group, 8 patients subsequently developed a rising PSA level. The 5-year bNED rate was 88%. SVI was the strongest predictor of outcome, with a 5-year bNED rate of 94% for those without SVI and 65% for those with SVI (p = 0.0002). SVI was the only significant factor in Cox proportional hazards regression analysis in the ART cohort. For the SRT group, 20 patients developed a rising PSA level after RT. The 5-year bNED rate was 66% for all SRT patients, and 43% and 78% in those with a persistently detectable PSA and those with a delayed rise in PSA, respectively. In the Cox proportional hazards regression analysis, this subdivision of SRT was statistically significant. Moreover, when the Cox model included all patients and variables, the timing of RT (ART vs. SRT) was an independent correlate of bNED, as was androgen ablation. CONCLUSION: For RP patients with high-risk pathologic features, the timing of postoperative RT and the PSA status after RP were strong determinants of outcome. Because of the potential confounding factors, direct comparisons of ART and SRT are problematic; however, ART is extremely effective and offers the surest approach for maintaining biochemical control.

Quality of life after treatment for localized prostate cancer: differences based on treatment modality.

PURPOSE: Brachytherapy with 103palladium (103Pd) is an increasingly administered treatment modality for localized prostate cancer. We compared general and disease specific health related quality of life after 103Pd treatment, radical prostatectomy and external beam radiation therapy given during the same time frame. MATERIALS AND METHODS: We performed a retrospective cross-sectional survey study of patients treated at a single community medical center between 1995 and 1999. We mailed 5 validated health related quality of life survey instruments to 269, 142 and 222 men who underwent radical prostatectomy, 103Pd treatment and external beam radiation therapy, respectively, with a response rate of greater than 80% in all groups. RESULTS: General health related quality of life assessed by the SF-36 showed the same scores in patients who underwent prostatectomy and 103Pd treatment. The University of California-Los Angeles Prostate Cancer Index was used to assess bowel, urinary and sexual function/bothersomeness. External beam radiation therapy reported was associated with worse bowel function and greater bowel bothersomeness. Prostatectomy was associated with worse urinary function compared to 103Pd and external beam radiation therapy. Prostatectomy was associated with worse sexual function than 103Pd or external beam radiation therapy, although nerve sparing surgery and erectile aids minimized the difference. American Urological Association symptom scores were initially higher for 103Pd but became equal to those in the other groups in patients treated greater than 12 months from survey time. Disease-free men who underwent prostatectomy and 103Pd brachytherapy were equally confident that cancer would not recur in the future. Satisfaction rates were equivalent and biochemical failure significantly decreased satisfaction in all groups. CONCLUSIONS: While general health related quality of life was mostly unaffected by the 3 most common treatments for prostate cancer, there were differences in bowel, urinary and sexual function. This information may aid patients in the decision making process.

Overexpression of p53 in prostate carcinoma is associated with improved overall survival but not predictive of response to radiotherapy.

p53 gene mutations are among the most common specific genetic alterations in human cancer. Inactivation of p53 and subsequent protein accumulation has been implicated in a variety of human malignancies and associated with prostate cancer progression. In this study, we assessed p53 protein overexpression and gene mutations in prostate carcinoma and investigated associations between p53 alterations and clinicopathological parameters, survival, and response to radiotherapy. We evaluated 58 archival formalin-fixed, paraffin-embedded prostate carcinomas to detect abnormal p53 nuclear protein accumulation using immunohistochemistry. p53 mutational status of tumor DNA was evaluated using polymerase chain reaction-single-strand conformation polymorphism analysis of exons 5-9 and confirmed by direct DNA sequencing. Univariate and multivariate statistical analysis was used to determine the association of p53 status with clinical characteristics and response to radiotherapy. Overexpression of p53 was detected in 42 (72%) of 58 primary prostate carcinomas, but was undetectable in 7 samples of benign prostatic hyperplasias or 5 samples of normal prostate tissue. p53 exon 5-9 mutations were detected in 8 (14%) of 58 patient specimens. p53 mutational status, but not overexpression, was associated with higher Gleason scores (p=0.0145). Neither p53 overexpression nor mutation was associated with clinical stage, biochemical disease-free probability, or predictive of response to radiotherapy. p53 protein accumulation was inversely associated with improved overall survival (p=0.0108). Our studies demonstrate that p53 protein accumulation is a frequent alteration in prostate cancer. The disparity between p53 protein overexpression and p53 exon 5-9 mutations suggests the possibility of mutations outside this region or stabilization of wild-type p53 by alternative mechanisms. In our patient population, p53 protein overexpression or mutational status was not predictive of outcome in patients treated with radiation therapy. Additional studies are needed to further evaluate the association between p53 protein overexpression and improved overall survival.

Radiation therapy for clinically localized prostate cancer: a multi-institutional pooled analysis.

CONTEXT: Prostate-specific antigen (PSA) evaluation leads to the early detection of both prostate cancer and recurrences following primary treatment. Prostate-specific antigen outcome information on patients 5 or more years following treatment is limited and available mainly as single-institution reports. OBJECTIVES: To assess the likelihood and durability of tumor control using PSA evaluation 5 or more years after radical external beam radiation therapy and to identify pretreatment prognostic factors in men with early prostate cancer treated since 1988, the PSA era. DESIGN AND SETTING: Retrospective, nonrandomized, multi-institutional pooled analysis of patients treated with external beam radiation therapy alone between 1988 and 1995 at 6 US medical centers. Follow-up lasted up to a maximum of 9 years. Outcome data were analyzed using Cox regression and recursive partitioning techniques. PATIENTS: A total of 1765 men with stage T1b, T1c, and T2 tumors treated between 1988 and 1995 with external beam radiation. The majority (58%) of patients were older than 70 years and 24.2% had initial PSA values of 20 ng/mL or higher. A minimum of 2 years of subsequent follow-up was required for participation. MAIN OUTCOME MEASURE: Actuarial estimates of freedom from biochemical failure. RESULTS: The 5-year estimates of overall survival, disease-specific survival, and the freedom from biochemical failure are 85.0% (95% confidence interval [CI], 82.5%-87.6%), 95.1% (95% CI, 94.0%-96.2%), and 65.8% (95% CI, 62.8%-68.0%), respectively. The PSA failure-free rates 5 and 7 years after treatment for patients presenting with a PSA of less than 10 ng/mL were 77.8% (95% CI, 74.5%-81.3%), and 72.9% (95% CI, 67.9%-78.2%). Recursive partitioning analysis of initial PSA level, palpation stage, and the Gleason score groupings yielded 4 separate prognostic groups: group 1, included patients with a PSA level of less than 9.2 ng/mL; group 2, PSA level of at least 9.2 but less than 19.7 ng/mL; group 3, PSA level at least 19.7 ng/mL and a Gleason score of 2 to 6; and group 4, PSA level of at least 19.7 ng/mL and a Gleason score of 7 to 10. The estimated rates of survival free of biochemical failure at 5 years are 81 % for group 1, 69% for group 2, 47% for group 3, and 29% for group 4. Of the 302 patients followed up beyond 5 years who were free of biochemical disease, 5.0% relapsed from the fifth to the eighth year. CONCLUSIONS: Estimated PSA control rates in this pooled analysis are similar to those of single institutions. These rates indicate the probability of success for subsets of patients with tumors of several prognostic category groupings. These results represent a multi-institutional benchmark for evidence-based counseling of prostate cancer patients about radiation treatment.

PSA for outcome prediction and posttreatment evaluation following radiation for prostate cancer: do we know how to use it?

Pretreatment prostate-specific antigen (PSA) has been shown to be a powerful predictor of expected outcome after radiation for prostate cancer. Additional measures such as recursive partitioning analysis and PSA Cancer Volume calculations are further refining this useful tool to provide the greatest degree of prognostic information. The post-treatment PSA level is also being used as a means to assess therapeutic efficacy rapidly and objectively. Although no single PSA value has been shown to equate to long-term clinical tumor control consistently, consensus has been reached regarding the value of a rising PSA level as an early surrogate for tumor recurrence. Since the first introduction of PSA as a tumor marker, we have become much more comfortable with what it means, the ways it can help us, and how to use it.

High dose rate vaginal brachytherapy in early stage endometrial carcinoma: preliminary analysis.

From 1987 to 1993, 69 women diagnosed with FIGO stages I and II carcinoma of the endometrium underwent postoperative adjuvant irradiation (RT) under protocol with high dose rate (HDR) afterloading vaginal apex brachytherapy. All patients initially underwent total abdominal hysterectomy and bilateral salpingo-oopherectomy. Forty-four women received HDR brachytherapy alone and 25 received external beam RT as well as HDR brachytherapy. The median follow-up was 45 months. The 5-year disease-free survival was 92% and the overall survival rate was 79%. Multivariate Cox regression analysis revealed that grade, age, and stage were significant predictors of survival. The overall acute and late side effects were minimal. It appears that HDR vaginal brachytherapy is prevention of vaginal recurrence in endometrial carcinoma and should be considered an effective treatment option.

Prostate-specific antigen after radiation therapy. Prognosis by pretreatment level and post-treatment nadir.

After external beam radiation therapy, pretreatment prostate-specific antigen (PSA) is the most powerful predictor of outcome as measured PSA (biochemical) failure. The post-treatment nadir levels of PSA that predict best for subsequent freedom from PSA failure are debatable, and many nadir levels have been proposed as targets. Although lower nadirs generally are associated with superior outcomes, the identification of a single absolute nadir level was not selected at a recent ASTRO consensus conference. Rather, three consecutive PSA rises above the nadir, with date of failure at the midpoint between the nadir and first rise, were selected as a more useful end point for treatment failure.

Prostate-specific antigen for pretreatment prediction and posttreatment evaluation of outcome after definitive irradiation for prostate cancer.

PURPOSE: This study was undertaken to assess the predictive value of pretreatment prostate-specific antigen (PSA) and the difference between clinical and PSA disease-free status in patients with long-term follow-up after irradiation for prostatic carcinoma. Comparison of the distribution of prognostic factors between surgical and radiation series was also made. METHODS AND MATERIALS: From 1975-1989, 652 patients with clinical Stage A2-C prostatic adenocarcinoma were definitively irradiated using external beam therapy. One hundred and fifty patients with banked serum and up to 14 years follow-up have pretreatment PSA levels and 355 patients with up to 17 years follow-up have posttreatment values. Treatment failure was analyzed by tumor stage, grade, and four pretreatment PSA categories. Disease-progression was evaluated by clinical and biochemical (PSA) endpoints. Prognostic factors were compared to two surgical series. RESULTS: A significant difference was seen in clinical and PSA disease-free (PSA < or = 4.0 ng/ml) status based on tumor grade, stage, and pretreatment PSA category. Although the expected clinical outcome has been well-documented previously, results based on posttreatment PSA levels show 5-year disease-free survivals reduced by 10-16% and 10-year survivals lessened by 15-39% depending upon the particular tumor grade and stage. The earlier stage, lower grade tumors showed the largest difference between clinical and biochemical recurrence rates at the longest interval from treatment. Even more notable were the differences in the clinical and PSA disease-free rates based on the pretreatment PSA level. Comparing the irradiated patients to two surgical series showed that the former had a larger percentage of more advanced stage tumors with more unfavorable PSA levels as compared to prostatectomy patients. CONCLUSION: With long-term follow-up, the pretreatment PSA level continues to be a powerful predictor of clinical and biochemical outcome in patients irradiated for apparently localized prostate cancer. Differences between clinical and PSA outcome can be considerable, but oftentimes clinically insignificant. The distribution of prognostic factors between radiation and prostatectomy series seems to favor the latter.

Potential benefit of improved local tumor control in patients with prostate carcinoma.

BACKGROUND: In the case of prostate carcinoma, radiation therapy is a locally applied treatment modality in a malignancy known for systemic dissemination. Because significant efforts and resources currently are being consumed to improve local tumor control, failure patterns and potential curative gain deserve appropriate assessment. METHODS: From 1975-1989, 647 patients with clinically localized prostate carcinoma were definitively irradiated for biopsy-proven adenocarcinoma of the prostate. Failure patterns were examined, and survival advantage based on improvement in either local or distant disease control was calculated. Distant metastatic rate and cause-specific survival analyses were used as parameters by which to compare the outcome for patients in whom local tumor control was achieved with patients who experienced local failure, thereby assessing further the importance of the effectiveness of locally applied therapy. RESULTS: Three hundred ninety-two (61%) patients at the time of this writing were clinically disease free. Sixty-two (10%) patients failed locally only, 133 (20%) distantly only, and 60 (9%) developed local and distant recurrent disease. Both local and distant failure rates were higher in patients with more advanced stage lesions at presentation, and distant failure rates significantly increased in patients with less differentiated tumors. Pretreatment prostate-specific antigen was found to be useful in predicting recurrence patterns. Overall, there appeared to be more potential for improvement in survival secondary to reducing distant metastasis. The distant survival advantage (DSA) of reducing distant metastases, compared with the local survival advantage (LSA) of improving local tumor control, was 26 versus 14%. Although DSA was greater than LSA within each stage category, the potential to improve survival was most significant in the Stage C group, where DSA was 35% and LSA 16%. Although LSA varied little according to tumor grade, DSA was dependent on tumor grade and varied from 13% for well differentiated lesions to 38% for poorly differentiated lesions. Distant failure free survival at 10 years was 63% for patients with local control and 45% for those with local failure (P = 0.01). Similarly, 10-year cause-specific survival was 75% in locally controlled patients compared with 48% for those with local recurrence (P < 0.001). CONCLUSIONS: Although better local tumor control should translate into at least modest survival gain for patients with prostate carcinoma, additional advantage may be seen with improved systemic therapy or perhaps earlier diagnosis to reduce further the distant metastasis rate.

Carcinoma of the prostate: race as a prognostic indicator in definitive radiation therapy.

PURPOSE: To characterize the racial differences in prognostic factors and treatment outcome for patients undergoing radiation therapy for carcinoma of the prostate. MATERIALS AND METHODS: From January 1975 through December 1989, 489 white and 157 black men with carcinoma of the prostate underwent irradiation. Factors analyzed were patient age, tumor stage and grade, prostate-specific antigen (PSA) levels, and disease-control and survival rates. RESULTS: More black patients than white patients were found to have poorly differentiated tumors. Black patients had higher PSA levels before and after treatment, resulting in a higher distant failure rate and poorer overall, cause-specific, and disease-free survival rates. CONCLUSION: Black men have more aggressive prostatic tumors, a higher rate of metastasis, and a poorer survival rate than do white men.

Treatment of clinical local failure after radiation therapy for prostate carcinoma.

From a base population of 634 patients with prostate cancer treated by external beam therapy with a median followup of 8 years and 123 patients treated by interstitial brachytherapy with 125iodine (125I) isotope with a median followup of 13 years, those with local failure only were identified. There were 57 external beam radiotherapy (9%) and 15 125I (12%) treated patients with local failure only among the base population. All but 3 patients (2 given external beam radiotherapy and 1 given 125I) were treated with hormonal manipulation without extirpative surgery. The overall cancer-specific median survival with hormonal therapy from the date of local failure was 70 months for 55 patients treated by external beam radiotherapy and 87 months for 14 treated by 125I. Patients with low grade, small volume tumors most likely to benefit from salvage surgery are also those who will experience prolonged survival with hormonal therapy. Patients with local failure only treated by hormonal manipulation had statistically longer cancer-specific survival rates from the date of failure than did similarly treated patients experiencing distant failure with local failure. This finding suggests a difference in the biological aggressiveness between tumors associated with distant and local failure versus local failure only. To select the patients with local failure only who would be candidates for the potentially benefited by salvage surgery, those with pretreatment stage A or B disease who were less than 72 years old were identified. A total of 17 patients treated by external beam radiotherapy and 7 treated by 125I fulfilled these criteria. Therefore, as determined by local failure only, patient age and pre-radiation clinical stage, only 2 to 5% of the patients treated with radiation modalities are ultimately optimal candidates for salvage surgery.

Prognostic significance of post-irradiation prostate biopsies.

Over the last 2 decades, the prognostic significance of post-irradiation prostate biopsy has been debated. Studies with long-term follow-up have shown a predictive effect with regard to local tumor failure and disease-free survival. More recently collected data involve the use of prostate ultrasound and prostate-specific antigen; the latter appears to be a good prognostic indicator on its own. Currently, the practical usefulness of post-treatment biopsy for clinically undetectable disease remains undefined, since definitive therapy for positive findings cannot be widely applied, carries significant morbidity, and, as yet, is of questionable benefit. Further study is certainly necessary, and it is perhaps under these conditions that this post-therapy procedure should be used.

Flow cytometric DNA content and clinical outcome in patients with non-small cell lung cancer given postoperative radiation therapy.

DNA content by flow cytometry was assessed in 47 cases from a series of 130 patients with non-small cell lung carcinoma (NSCLC) given radiation therapy postoperatively. This was done in an attempt to identify which patients might benefit, or not benefit, from postoperative radiotherapy. From archival formalin-fixed paraffin-embedded specimens, 16 of the 47 cases (34%) had DNA diploid tumors while 31 cases (66%) were nondiploid. A diploid DNA content was significantly related to improved overall survival (P = 0.0061) and tumor-free survival (P = 0.0167) but not with frequency of tumor recurrence within the irradiated field. Histological grade was not significantly related to overall survival, tumor-free survival, or frequency of in-field tumor recurrence. DNA content was found in this study of NSCLC patients irradiated postoperatively to be a useful marker for predicting survival but not for predicting local recurrence.

The significance of post-irradiation prostate biopsy with long-term follow-up.

Ninety-four patients, Stage A2-C, definitively irradiated for adenocarcinoma of the prostate from 1975 to 1981 underwent digitally directed transperineal needle biopsy of a clinically negative prostate gland at least 18 months post-therapy. Ten of 55 patients (18%) treated with Iodine-125 implantation and 7 of 39 patients (18%) externally irradiated were found to have positive biopsy specimens. Overall, clinical local failure occurred in 53% of patients with positive biopsy results but in only 18% with negative specimens, p = .006. The false negative biopsy rate in patients treated with I-125 was nearly three times that for external beam, 24% versus 9%, perhaps because of the greater possibility of inhomogeneous dose distribution with I-125, allowing for a higher degree of sampling error. Actuarial local failure at 5 years was 44% versus 8% with positive and negative biopsies, respectively, and 75% versus 24% at 10 years (p = .0001). The distant metastatic rate was twice as high in biopsy-positive as compared to biopsy-negative patients, 71% versus 35%, p = .015. Actuarially, only 19% of patients with a positive biopsy are NED at 10 years as compared to 62% of those with a negative biopsy (p = .0001). PSA values are supportive in those patients thought to be disease-free. The incidence of positive biopsy and associated local recurrence are in keeping with clinical treatment failure rates as reported in multiple studies to date.