R.G. Stock

THE AMERICAN BRACHYTHERAPY SOCIETY RECOMMENDATIONS FOR PERMANENT PROSTATE BRACHYTHERAPY POSTIMPLANT DOSIMETRIC ANALYSIS

PURPOSEnThe purpose of this report is to establish guidelines for postimplant dosimetric analysis of permanent prostate brachytherapy.nnnMETHODSnMembers of the American Brachytherapy Society (ABS) with expertise in prostate dosimetry evaluation performed a literature review and supplemented with their clinical experience formulated guidelines for performing and analyzing postimplant dosimetry of permanent prostate brachytherapy.nnnRESULTSnThe ABS recommends that postimplant dosimetry should be performed on all patients undergoing permanent prostate brachytherapy for optimal patient care. At present, computed tomography (CT)-based dosimetry is recommended, based on availability cost and the ability to image the prostate as well as the seeds. Additional plane radiographs should be obtained to verify the seed count. Until the ideal postoperative interval for CT scanning has been determined, each center should perform dosimetric evaluation of prostate implants at a consistent postoperative interval. This interval should be reported. Isodose displays should be obtained at 50%, 80%, 90%, 100%, 150%, and 200% of the prescription dose and displayed on multiple cross-sectional images of the prostate. A dose-volume histogram (DVH) of the prostate should be performed and the D90 (dose to 90% of the prostate gland) reported by all centers. Additionally, the D80, D100, the fractional V80, V90, V100, V150 and V200 (i.e., the percentage of prostate volume receiving 80%, 90%, 100%, 150%, and 200% of the prescribed dose, respectively), the rectal, and urethral doses should be reported and ultimately correlated with clinical outcome in the research environment. On-line real-time dosimetry, the effects of dose heterogeneity, and the effects of tissue heterogeneity need further investigation.nnnCONCLUSIONnIt is essential that postimplant dosimetry should be performed on all patients undergoing permanent prostate brachytherapy. Guidelines were established for the performance and analysis of such dosimetry.

IDENTIFICATION OF PATIENTS AT INCREASED RISK FOR PROLONGED URINARY RETENTION FOLLOWING RADIOACTIVE SEED IMPLANTATION OF THE PROSTATE

PURPOSEnUrinary 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.nnnMATERIALS AND METHODSnA 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.nnnRESULTSnUrinary 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%).nnnCONCLUSIONSnThe 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.

Serum Interleukin-8 is Elevated in Men with Prostate Cancer and Bone Metastases

Aalinkeel et al. (1) have recently reported that gene expression of angiogenic factors correlates with metastatic potential of prostate cancer cells. The rationale for the study of Aalinkeel et al. is that a variety of growth factors, among them interleukin-8 (il-8), can induce angiogenesis (2). Further, parathyroid hormone related peptide (PTHrP) acts to induce il-8 production in prostate cancer cells via an intracrine pathway independent of its classical nuclear localization sequence. This novel pathway could mediate the effects of PTHrP on the progression of prostate cancer (3). We measured il-8 in the serum of 39 men with biopsy-proven prostate cancer. Their average age was 69 +/- 9 (mean +/- SD). Serum il-8 was measured with an automated chemiluminometric high sensitivity il-8 protein assay (Immulite, Diagnostic Products Corporation, Los Angeles, CA). We noted a significant elevation of il-8 in men with bone metastases, diagnosed by Tc-99 MDP bone scan, when compared to men with localized disease (Figure 1). Aalinkeel et al. found that il-8 was significantly higher in the more metastatic PC-3 and DU-145 prostate cancer cell lines, when compared to the poorly metastatic LnCAP cells. The results of our study of il-8 in men with prostate cancer support the findings of Aalinkeel et al. Therefore, new anti-angiogenic therapies targeting specific genes controlling prostate tumor metastasis may be of benefit in treating prostate cancer.

Putative protein markers in the sera of men with prostatic neoplasms

To describe the preliminary identification of serum proteins that may be diagnostic markers in prostate cancer.

C‐reactive protein is significantly associated with prostate‐specific antigen and metastatic disease in prostate cancer

To further analyse the relationship of c‐reactive protein (CRP) levels to prostate cancer, by measuring CRP in men with prostate cancer and benign prostatic hypertrophy (BPH), as chronic inflammation has long been linked to cancers with an infectious cause and CRP is a nonspecific marker for inflammation, associated with prostate cancer incidence and progression.

The effect of prognostic factors on therapeutic outcome following transperineal prostate brachytherapy

The objectives of this study were to examine the effect of both disease and treatment related prognostic factors on biochemical control and post-treatment biopsy. Two-hundred fifty-eight patients underwent interactive ultrasound guided transperineal prostate implantation for T1-T2 prostate cancer using Iodine-125 (139 patients) and Palladium-103 (119 patients) and were followed from 6-67 months (median, 19). Hormonal therapy with 3 months of leuprolide and flutamide prior to implantation and two months given after the implant was used in 96 patients. Pre-treatment prostate-specific antigen (PSA) had the most significant effect on biochemical failure. Freedom from biochemical failure (FFBF) rates at 4 years were 75% for patients with PSA 1.3-10 ng/ml (144), 74% for patients with PSA 10.1-20 ng/ml (73), and 34% for patients with PSA > 20 ng/ml (41) (P = 0.0004). Gleason score also had a significant effect on FFBF rates. Four-year rates were 81%, 65% and 47% for patients with scores of 2-4 (68), 5-6 (130), and > or = 7 respectively (60) (P = 0.01). These two factors were also significant in multivariate analysis (P = 0.002, 0.007, respectively). Gleason score was the only factor to significantly affect post-treatment biopsy results. Patients with scores of 2-6 had 85% (63/ 74) negative 2-year biopsies versus 62% (13/21) for patients with scores > or = 7 (P = 0.02). Low-risk patients (PSA < or = 10 ng/ml, scores < 7 and stage < T2a) had a 4-year FFBF rate of 88% as compared to 60% for high-risk patients (PSA > 10 ng/ml, score > 6 or stage > or = T2b) (P = 0.02) and had a 95% negative biopsy rate versus 76% for high-risk patients (P = 0.06). Low-risk patients demonstrate high FFBF and negative biopsy rates following implantation. Patients presenting with higher risk prognostic factors such as PSA > 20 ng/ml or Gleason scores > or = 7 may require more aggressive treatment regimens.

Laparoscopic Pelvic Lymph Node Dissection Combined with Real-time Interactive Transrectal Ultrasound Guided Transperineal Radioactive Seed Implantation of the Prostate

Laparoscopic pelvic lymph node dissection with real-time interactive transrectal ultrasound guided transperineal radioactive seed implantation is a new method of treatment for localized carcinoma of the prostate. A total of 58 patients with clinically confined prostate cancer and negative seminal vesicle biopsies underwent staging laparoscopic pelvic lymph node dissection immediately followed by prostate implantation: 50 had 125iodine and 8 had 103palladium implants. Mean operating time was 226 minutes (range 120 to 475), mean blood loss was 57 cc (range 5 to 400) and average hospital stay was 2.2 days (range 0.5 to 8). At a mean followup of 12 months (range 6 to 24), complications included proctitis in 1.7% of the cases, dysuria in 24%, nocturia in 21% and outlet obstruction in 17%. Erectile function remained unchanged. Prostate volume decreased to 58.9% of the pretreatment value by 12 months and to 44.3% by 24 months. Mean prostate specific antigen level was 18.4 +/- 26.3 ng./ml. before treatment, 3.4 +/- 3.9 ng./ml. at 6 months, 2.3 +/- 2.3 ng./ml. at 12 months and 4.9 +/- 6.0 ng./ml. at 24 months (1.2 +/- 1.0 ng./ml. for patients with no evidence of disease). Of the patients 15.8% had local failure at 18 to 24 months as determined by positive transrectal ultrasound guided biopsy. Five of 58 patients (8.6%) had persistently elevated prostate specific antigen levels, only 1 of whom had a positive biopsy. Laparoscopic pelvic lymph node dissection with transrectal ultrasound guided implantation is a safe and promising mode of therapy for patients with localized prostate cancer.

Phase II Trial of Concurrent Sunitinib and Image-Guided Radiotherapy for Oligometastases

Background Preclinical data suggest that sunitinib enhances the efficacy of radiotherapy. We tested the combination of sunitinib and hypofractionated image-guided radiotherapy (IGRT) in a cohort of patients with historically incurable distant metastases. Methods Twenty five patients with oligometastases, defined as 1–5 sites of active disease on whole body imaging, were enrolled in a phase II trial from 2/08 to 9/10. The most common tumor types treated were head and neck, liver, lung, kidney and prostate cancers. Patients were treated with the recommended phase II dose of 37.5 mg daily sunitinib (days 1–28) and IGRT 50 Gy (days 8–12 and 15–19). Maintenance sunitinib was used in 33% of patients. Median follow up was 17.5 months (range, 0.7 to 37.4 months). Results The 18-month local control, distant control, progression-free survival (PFS) and overall survival (OS) were 75%, 52%, 56% and 71%, respectively. At last follow-up, 11 (44%) patients were alive without evidence of disease, 7 (28%) were alive with distant metastases, 3 (12%) were dead from distant metastases, 3 (12%) were dead from comorbid illness, and 1 (4%) was dead from treatment-related toxicities. The incidence of acute grade ≥ 3 toxicities was 28%, most commonly myelosuppression, bleeding and abnormal liver function tests. Conclusions Concurrent sunitinib and IGRT achieves major clinical responses in a subset of patients with oligometastases. Trial Registration ClinicalTrials.gov NCT00463060

Early use of a phosphodiesterase inhibitor after brachytherapy restores and preserves erectile function.

Associate Editor

Seminal vesicle biopsy: Accuracy and implications for staging of prostate cancer

OBJECTIVESnSeminal vesicle biopsy (SVB) is a new technique for detecting the spread of prostate cancer to the seminal vesicles. A comparison of findings following SVB in patients undergoing radiation therapy with pathologic findings following radical retropubic prostatectomy (RRP) was made to evaluate the accuracy of this test and its use in the staging of prostate cancer.nnnMETHODSnFour hundred nine patients with clinically localized adenocarcinoma of the prostate gland were evaluated for treatment: 222 patients underwent SVB prior to radiation therapy and 187 patients underwent RRP. Clinical stages in patients undergoing SVB included T1a (1 patient), T1b (4), T1c (35), T2a (49), T2b (96), and T2c (37); RRP clinical stages included T1b (3 patients), T1c (48), T2a (57), T2b (66), and T2c (13). The Gleason scores in patients undergoing SVB were 2 to 4 in 50 men, 5 to 6 in 110 men, and 7 and greater in 62 men; the Gleason scores in patients undergoing RRP were 2 to 4 in 53 men, 5 to 6 in 94 men, and 7 and greater in 40 men. Prostate-specific antigen (PSA) values ranged from 1.3 to 190 ng/mL (median 10.75) in men undergoing SVB and ranged from 0.5 to 140.6 ng/mL (median 9.0) in men undergoing RRP.nnnRESULTSnThe overall incidence of seminal vesicle involvement as determined by the two techniques was the same. Seminal vesicle involvement was found in 33 of 222 patients (15%) undergoing SVB and in 27 of 187 (14%), of the RRP specimens (P = 0.9). When the two groups were further divided by three prognostic categories (clinical stage, PSA level, and grade), there was no difference in the incidence of seminal vesicle involvement between the two methods, except in the patients with Gleason score of 4 or less. In these patients, 5 of 53 (9%) had seminal vesicle involvement in the RRP group, compared with none of the 50 men in the SVB group (P = 0.02). Disease that was not organ confined was found in 69 of 187 prostatectomy specimens (37%). Of these patients, 27 of 69 (39%) had seminal vesicle involvement.nnnCONCLUSIONSnSVB is an accurate method of detecting seminal vesicle invasion based on comparisons with radical prostatectomy findings. Its importance lies in its ability to detect a large percentage of patients with non-organ-confined disease and in its use in modifying treatment planning accordingly.