Kevin McGeagh

A Pilot Study of Intensity Modulated Radiation Therapy with Hypofractionated Stereotactic Body Radiation Therapy (SBRT) Boost in the Treatment of Intermediate- to High-Risk Prostate Cancer

Clinical data suggest that large radiation fractions are biologically superior to smaller fraction sizes in prostate cancer radiotherapy. The CyberKnife is an appealing delivery system for hypofractionated radiosurgery due to its ability to deliver highly conformal radiation and to track and adjust for prostate motion in real-time. We report our early experience using the CyberKnife to deliver a hypofractionated stereotactic body radiation therapy (SBRT) boost to patients with intermediate- to high-risk prostate cancer. Twenty-four patients were treated with hypofractionated SBRT and supplemental external radiation therapy plus or minus androgen deprivation therapy (ADT). Patients were treated with SBRT to a dose of 19.5 Gy in 3 fractions followed by intensity modulated radiation therapy (IMRT) to a dose of 50.4 Gy in 28 fractions. Quality of life data were collected with American Urological Association (AUA) symptom score and Expanded Prostate Cancer Index Composite (EPIC) questionnaires before and after treatment. PSA responses were monitored; acute urinary and rectal toxicities were assessed using Common Toxicity Criteria (CTC) v3. All 24 patients completed the planned treatment with an average follow-up of 9.3 months. For patients who did not receive ADT, the median pre-treatment PSA was 10.6 ng/ml and decreased in all patients to a median of 1.5 ng/ml by 6 months post-treatment. Acute effects associated with treatment included Grade 2 urinary and gastrointestinal toxicity but no patient experienced acute Grade 3 or greater toxicity. AUA and EPIC scores returned to baseline by six months post-treatment. Hypofractionated SBRT combined with IMRT offers radiobiological benefits of a large fraction boost for dose escalation and is a well tolerated treatment option for men with intermediate- to high-risk prostate cancer. Early results are encouraging with biochemical response and acceptable toxicity. These data provide a basis for the design of a phase II clinical trial.

Low incidence of new biochemical and clinical hypogonadism following hypofractionated stereotactic body radiation therapy (SBRT) monotherapy for low- to intermediate-risk prostate cancer

BackgroundThe CyberKnife is an appealing delivery system for hypofractionated stereotactic body radiation therapy (SBRT) because of its ability to deliver highly conformal radiation therapy to moving targets. This conformity is achieved via 100s of non-coplanar radiation beams, which could potentially increase transitory testicular irradiation and result in post-therapy hypogonadism. We report on our early experience with CyberKnife SBRT for low- to intermediate-risk prostate cancer patients and assess the rate of inducing biochemical and clinical hypogonadism.MethodsTwenty-six patients were treated with hypofractionated SBRT to a dose of 36.25 Gy in 5 fractions. All patients had histologically confirmed low- to intermediate-risk prostate adenocarcinoma (clinical stage ≤ T2b, Gleason score ≤ 7, PSA ≤ 20 ng/ml). PSA and total testosterone levels were obtained pre-treatment, 1 month post-treatment and every 3 months thereafter, for 1 year. Biochemical hypogonadism was defined as a total serum testosterone level below 8 nmol/L. Urinary and gastrointestinal toxicity was assessed using Common Toxicity Criteria v3; quality of life was assessed using the American Urological Association Symptom Score, Sexual Health Inventory for Men and Expanded Prostate Cancer Index Composite questionnaires.ResultsAll 26 patients completed the treatment with a median 15 months (range, 13-19 months) follow-up. Median pre-treatment PSA was 5.75 ng/ml (range, 2.3-10.3 ng/ml), and a decrease to a median of 0.7 ng/ml (range, 0.2-1.8 ng/ml) was observed by one year post-treatment. The median pre-treatment total serum testosterone level was 13.81 nmol/L (range, 5.55 - 39.87 nmol/L). Post-treatment testosterone levels slowly decreased with the median value at one year follow-up of 10.53 nmol/L, significantly lower than the pre-treatment value (p < 0.013). The median absolute fall was 3.28 nmol/L and the median percent fall was 23.75%. There was no increase in biochemical hypogonadism at one year post-treatment. Average EPIC sexual and hormonal scores were not significantly changed by one year post-treatment.ConclusionsHypofractionated SBRT offers the radiobiological benefit of a large fraction size and is well-tolerated by men with low- to intermediate-risk prostate cancer. Early results are encouraging with an excellent biochemical response. The rate of new biochemical and clinical hypogonadism was low one year after treatment.

Robotic-assisted prostatectomy and open radical retropubic prostatectomy for locally-advanced prostate cancer: multi-institution comparison of oncologic outcomes

Purpose: Robotic-assisted laparoscopic prostatectomy (RALP) offers reportedly comparable oncologic outcomes for localized disease compared with open radical retropubic prostatectomy (ORRP). However, the oncologic efficacy of RALP in locally-advanced prostate cancer (PCa) is less clear. We report and compare our experience with RALP and ORRP in men with locally advanced PCa. Methods: Patients with locally advanced PCa (stage T3 or greater) were identified in both robotic and open cohorts. Clinicopathologic features including age, clinical stage, prostate-specific antigen, surgical margins, and Gleason score were reviewed. We further examined the incidence of positive surgical margins, the effect of the surgical learning curve on margins, and the need for adjuvant therapy. Results: From 1997 to 2010, 1,011 patients underwent RALP and 415 patients were identified who underwent radical retropubic prostatectomy (RRP) across four institutions. 140 patients in the RALP group and 95 in the RRP group had locally advanced PCa on final pathology. The overall robotic positive margin rate 47.1% compared with 51.4% in the RRP group. A trend towards a lower positive margin rate was seen after 300 cases in the RALP group, with 66.7% positive margin rate in the first 300 cases compared with 41.8% in the latter 700 cases. In addition, a lower incidence of biochemical recurrence was also noted in the latter cases (30.6% vs. 9.5%). Conclusions: Up to 2 out of 3 men undergoing RALP for locally-advanced PCa had positive margins during our initial experience. However, with increasing surgeon experience the overall positive margin rate decreased significantly and was comparable to the positive margin rate for patients with locally advanced disease undergoing ORRP over four academic institutions. We also noted a lower incidence of biochemical recurrence with increasing RALP experience, suggesting better oncologic outcomes with higher volume. Given this data, RALP has comparable oncologic outcomes compared to ORRP, especially with higher volume surgeons.

Histopathologic effects of hypofractionated robotic radiation therapy on malignant and benign prostate tissue.

We describe the first histopathologic analysis of prostatic tissue following hypofractionated robotic radiation therapy. A 66 year-old man presented with stage II, low risk adenocarcinoma of the prostate and underwent elective conformal hypofractionated radiation therapy. His pretreatment evaluation revealed T1c adenocarcinoma, Gleasons grade 3 + 3 = 6 and a prostate specific antigen (PSA) level of 4.87 ng/ml. Hypofractionated radiation therapy (37.5 Gy in five daily fractions of 7.5 Gy) was completed on an Internal Review Board approved protocol. One year later, he developed progressive urinary retention. Transurethral prostatic resection was performed to alleviate obstructive symptoms. Bilobar hypertrophy was observed without evidence of stricture. Histolopathologic analyses of resected prostate tissues revealed changes consistent with radiation treatment, including cellular changes, inflammation, glandular atrophy and hyperplasia. There was no evidence of residual cancer, fibrosis or necrosis. The patients postoperative course was uneventful with post-treatment PSA of 0.5 ng/ml and residual grade 1 stress incontinence.

Correlation of HOXD3 promoter hypermethylation with clinical and pathologic features in screening prostate biopsies

Molecular markers that can discriminate indolent cancers from aggressive ones may improve the management of prostate cancer and minimize unnecessary treatment. Aberrant DNA methylation is a common epigenetic event in cancers and HOXD3 promoter hypermethylation (H3PH) has been found in prostate cancer. Our objective was to evaluate the relationship between H3PH and clinicopathologic features in screening prostate biopsies.

Does pure robotic partial nephrectomy provide similar perioperative outcomes when compared to the combined laparoscopic–robotic approach?

Laparoscopic and robotic partial nephrectomy have become the preferred option for surgical management of incidentally discovered small renal tumors. Currently there is no consensus on which aspects of the procedure should be performed laparoscopically versus robotically. We believe that combining a laparoscopic exposure and hilar dissection followed by tumor extirpation and renorrhaphy with robotic assistance provides improved perioperative outcomes compared to a pure robotic approach alone. We performed a comparison of perioperative outcomes between combined laparoscopic–robotic partial nephrectomy—or hybrid procedure—and pure robotic partial nephrectomy (RPN). A multi-center retrospective analysis of patients undergoing RPN and hybrid PN using the da Vinci S system® was performed. Patient data were reviewed for demographic and perioperative variables. Statistical analysis was performed using the Welch t test and linear regression, and nonparametric tests with similar significance results. Thirty-one patients underwent RPN while 77 patients underwent hybrid PN between 2007 and 2011. Preoperative variables were comparable in both groups with the exception of lesion size and nephrometry score which were significantly higher in patients undergoing hybrid PN. Length of surgery, estimated blood loss and morphine used were significantly less in the hybrid group, while warm ischemia time was significantly longer. The difference in WIT was accounted for in this data by adjusting for nephrometry score. In our multi-center series, the hybrid approach was associated with a shorter operative time, reduced blood loss and lower narcotic usage. We believe this approach is a valid alternative to RPN.