A Multi-Institutional Analysis of Prostate Cancer Patients With or Without 68Ga-PSMA PET/CT Prior to Salvage Radiotherapy of the Prostatic Fossa

Introduction68Ga-PSMA PET/CT is associated with unprecedented sensitivity for localization of biochemically recurrent prostate cancer at low PSA levels prior to radiotherapy. Aim of the present analysis is to examine whether patients undergoing postoperative, salvage radiotherapy (sRT) of the prostatic fossa with no known nodal or distant metastases on conventional imaging (CT and/or MRI) and on positron emission tomography/computed tomography (68Ga-PSMA PET/CT) will have an improved biochemical recurrence-free survival (BRFS) compared to patients with no known nodal or distant metastases on conventional imaging only.Material and MethodsThis retrospective analysis is based on 459 patients (95 with and 364 without 68Ga-PSMA PET/CT). BRFS (PSA < post-sRT Nadir + 0.2 ng/ml) was the primary study endpoint. This was first analysed by Kaplan-Meier and uni- and multivariate Cox regression analysis for the entire cohort and then again after matched-pair analysis using tumor stage, Gleason score, PSA at time of sRT and radiation dose as matching parameters.ResultsMedian follow-up was 77.5 months for patients without and 33 months for patients with 68Ga-PSMA PET/CT. For the entire cohort, tumor stage (pT2 vs. pT3-4; p= <0.001), Gleason score (GS ≤ 7 vs. GS8-10; p=0.003), pre-sRT PSA (<0.5 vs. ≥0.5ng/ml; p<0.001) and sRT dose (<70 vs. ≥70Gy; p<0.001) were the only factors significantly associated with improved BRFS. This was not seen for the use of 68Ga-PSMA PET/CT prior to sRT (p=0.789). Matched-pair analysis consisted of 95 pairs of PCa patients with or without PET/CT and no significant difference in BRFS based on the use of PET/CT was evident (p=0.884).ConclusionThis analysis did not show an improvement in BRFS using 68Ga-PSMA PET/CT prior to sRT neither for the entire cohort nor after matched-pair analysis after excluding patients with PET-positive lymph node or distant metastases a priori. As no improved BRFS resulted with implementation of 68Ga-PSMA PET in sRT planning, sRT should not be deferred until the best “diagnostic window” for 68Ga-PSMA PET/CT.

Mechanisms of Delayed Lower Urinary Tract Stone Formation

Materials and methods:We analysed Holmium Laser Enucleation of Prostate (HOLEP) database consisting of 1300 patients who presented more than 18 months after undergoing the procedure with lower urinary tract symptoms (LUTS-voiding lower urinary tract symptoms, dysuria, haematuria, recurrent urinary tract infections-UTIs) second-ary to delayed lower urinary tract stone formation. Information was gathered from the case notes, imaging modalities, operation notes and pathology reports. Results:Three patients were identified who presented with delayed lower urinary tract stone formation 18 months after undergoing HOLEP. Case 1: A 68-year-old presented with a 4-cm mobile bladder stone on a retained prostatic fragment 29 months after HOLEP.Case 2: A 74-year-old presented with 2.5 cm bulbar urethral stone 18 months after HOLEP.Case 3: A 77-year-old presented with dystrophic calcification of the entire prostatic fossa 60 months after HOLEP. Conclusion:Delayed lower urinary tract stone presentation is unusual after HOLEP. Recurrent urethral pain, recurrent UTI, gross haematuria and voiding lower urinary tract symptoms in the presence of a lower urinary tract stone (bladder, prostate and urethra) with a radiolucent centre on a background of HOLEP should raise the suspicion that this may represent calcification on a prostatic tissue fragment or dystrophic calcification of the residual prostate/prostatic fossa. Careful morcellation, inspection of the prostatic fossa on withdrawing the morcellator for large residual prostate fragments still attached to the prostatic bed/bladder neck or simply stuck to the fossa (usually in a clot) will reduce the risk of retainment of such a significant prostatic fragment that can potentially cause complications in the future.

RTOG 3506 (STEEL): A study of salvage radiotherapy with or without enzalutamide in recurrent prostate cancer following surgery.

TPS5601 Background: Salvage radiotherapy (SRT) is an important intervention for men with prostate cancer (PCa) who experience biochemical recurrence (BCR) after radical prostatectomy (RP). These patients are in need of cure or else they will develop metastatic disease. NRG/RTOG 9601 (WU Shipley, N Eng J Med 2017) identified a survival benefit from the addition of androgen receptor (AR) inhibition to SRT that was most prominent in men with high-risk features. Enzalutamide (Enza) is a non-steroidal anti-androgen that improves survival in castration-resistant and -sensitive PCa. We hypothesized that enhanced AR suppression with Enza would augment the benefit of SRT + androgen deprivation therapy (ADT) in BCR with high risk features. Methods: RTOG 3506 (STEEL, NCT03809000) is a randomized phase II study of SRT in BCR after RP with a serum PSA ≥ 0.2 ng/mL active in the USA and Canada. Patients are stratified by number of high-risk features including Gleason score (8-10), locoregional node involvement at RP, seminal vesicle invasion, persistently elevated PSA after RP, and PSA > 0.7 ng/mL. All patients receive SRT with 2 years of ADT. The experimental arm also receives Enza 160 mg daily for 2 years. Patients are followed by PSA every 3 months. SRT can be highly individualized per treating physician beyond the mandatory treatment of the prostatic fossa. Treatment of the pelvis and/or para-aortic nodes, as well as sequential or concurrent boosts to a prostatic fossa mass and/or suspicious lymph nodes, are allowed options. This permits individualization of radiotherapy guided by CT, MRI, PET, and/or biopsy findings. The primary goal of this study is to determine whether SRT enhanced ADT with Enza, will improve progression-free survival (PFS) compared to SRT with standard ADT. PFS defined as the first occurrence of biochemical failure, clinical failure, or initiation of new anticancer treatment. STEEL is designed to demonstrate a 35% reduction in the risk of progression at 5 years. An accrual goal of 242 patients will provide 80% power with a one-sided alpha = 0.10. Secondary endpoints include disease control rates, acute and late physician- and patient-reported toxicity, and quality of life. This study was activated in February 2019. Site recruitment and activation are underway. Conclusions: There is an unmet and urgent need for individualized strategies to optimize systemic therapy used with SRT for men with BCR. Outcomes from this study will further clarify the approach to systemic therapy for SRT in high-risk BCR patients. Support: Provided by Pfizer. Clinical trial information: NCT03809000 .

Is complete anatomical endoscopic laser enucleation of the prostate always necessary? Yes, it is!

Introduction: Thulium laser enucleation of the prostate is gaining popularity due to its short learning curve and low postoperative morbidity. The aim of Thulium laser enucleation of the prostate is the complete endoscopic enucleation of the adenoma. We report an unusual case of bladder outlet obstruction developed 6 weeks after Thulium laser enucleation of the prostate. Case description: A 74-year-old man complained of severe voiding phase symptoms lasting 2 weeks, starting 6 weeks after Thulium laser enucleation of the prostate. He underwent a transrectal ultrasound, which showed a wide prostatic fossa. A cystoscopy revealed that the prostatic fossa was filled with whitish tissue arising from two tiny residual adenomas. The obstructing tissue was resected with the aid of Thulium laser and the histopathology report showed necrotic prostatic glands. Conclusion: Partially enucleated and left inside adenoma may become necrotic and cause bladder outlet obstruction several weeks after Thulium laser enucleation of the prostate. Transrectal ultrasound control at the end of enucleation may help reduce this complication.

An investigation of metronomic photodynamic therapies for local prostate cancer: supplementary fluorescent photography and proteomic studies, as measurable parameters of this treatment.

Aim: To investigate the clinical effects of metronomic Photodynamic therapy in prostate cancer patients, using different chlorophyll based photosensitisers. Methods and materials: The patients who enrolled in this ethics approved Phase 1 prostate cancer trial were treated with a variable combination of targeted photo-dynamic therapies and coupled ultrasound energies, mediated through orally/sub-lingually administered chlorophyll based photosensitisers. The metronomic technique involves the repeated administration of both the photosensitiser(s) and energies over set time intervals. As scientific assessment of the prostate cancer effects, intra-treatment fluorescent photography of the prostate gland /prostatic fossa, together with proteomic based urine specimen studies were performed. Results: The clinical data involved 666 treatment episodes, 333 photosensitiser dosages and includes 3-5 years patient follow-up. The effects on the prostate symptoms and cancer are documented, prostate size reduction being a serendipitous finding. Real time fluorescent photography has documented qualitative reproducible data. The quantitative urinary proteomic studies demonstrated statistically significant results, as documentation of the known pathological effects, attributable to this treatment. Conclusion: This study has been shown to be safe and to meet the criteria required of a TGA Phase 1 trial and reports the clinical and investigational prostate cancer responses to the metronomic therapy, involving the three different photosensitisers. The scientific bases for this therapy have been validated with the real-time fluorescent photographic and proteomic analyses data, of particular interest and importance are the immune system results. The new word metapoptosis is suggested as the description for PDT induced malignant cell death in association with immune stimulation, as described in this study.

A study of prostatic fossa packing: a modified technique in Freyer’s prostatectomy for achieving hemostasis

Background: Benign prostatic hyperplasia is one of the most common old age related benign tumor of urinary tract of men. Though now a day the gold standard treatment is only TURP, but this facility is still out of reach for majority of rural population of India. The rate of complications has come down heavily but still complete hemostasis remains a major concern for these patients.Methods: This present study was conducted at the center from March 2014 to December 2016, the aim of present study was to see the effectiveness of bladder packing on blood loss, complications and comfort of patient in the cases of Benign prostatic hyperplasia (BPH) admitted at in patient department of surgery.Results: A Total of 90 cases of BPH (Benign Prostatic Hypertrophy) were operated by Freyer’s suprapubic transvesical prostatectomy. All the patients presented with symptoms of BPH. A detailed clinical history and examination of all patients was recorded and AUA (American Urological Association), International Prostate Symptom Score (IPSS) was calculated. On table clear urine was confirmed with naked eyes and no Foley’s traction was given. After 72 hours of the surgery, pack was removed, saline irrigation was continued for 5 days. The patient was discharged on the 8th post-operative day after removal of stitches.Conclusions: The prostatic fossa packing technique without any traction is effective in control of postoperative bleed, it is an acceptable option where transurethral resection of prostate(TURP) is not available.