Diagnosis and Treatment of Post-Prostatectomy Lymphedema: What's New?

Lymphedema is a chronic progressive disorder that significantly compromises patients' quality of life. In Western countries, it often results from cancer treatment, as in the case of post-radical prostatectomy lymphedema, where it can affect up to 20% of patients, with a significant disease burden. Traditionally, diagnosis, assessment of severity, and management of disease have relied on clinical assessment. In this landscape, physical and conservative treatments, including bandages and lymphatic drainage have shown limited results. Recent advances in imaging technology are revolutionizing the approach to this disorder: magnetic resonance imaging has shown satisfactory results in differential diagnosis, quantitative classification of severity, and most appropriate treatment planning. Further innovations in microsurgical techniques, based on the use of indocyanine green to map lymphatic vessels during surgery, have improved the efficacy of secondary LE treatment and led to the development of new surgical approaches. Physiologic surgical interventions, including lymphovenous anastomosis (LVA) and vascularized lymph node transplant (VLNT), are going to face widespread diffusion. A combined approach to microsurgical treatment provides the best results: LVA is effective in promoting lymphatic drainage, bridging VLNT delayed lymphangiogenic and immunological effects in the lymphatic impairment site. Simultaneous VLNT and LVA are safe and effective for patients with both early and advanced stages of post-prostatectomy LE. A new perspective is now represented by the combination of microsurgical treatments with the positioning of nano fibrillar collagen scaffolds (BioBridgeTM) to favor restoring the lymphatic function, allowing for improved and sustained volume reduction. In this narrative review, we proposed an overview of new strategies for diagnosing and treating post-prostatectomy lymphedema to get the most appropriate and successful patient treatment with an overview of the main artificial intelligence applications in the prevention, diagnosis, and management of lymphedema.

Perioperative Outcomes of Holmium Laser Enucleation of the Prostate: A Systematic Review.

INTRODUCTION: The aim of the study was to systematically review the literature and describe perioperative complications of holmium laser enucleation of the prostate (HoLEP), including the Clavien-Dindo classification of surgical complications. METHODS: All English language publications on HoLEP were evaluated. We followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines to evaluate PubMed®, Scopus®, and Web of Science™ databases from January 1, 1998, to June 1, 2020. RESULTS: Fifty-seven studies were included, for a total of 10,371 procedures. We distinguished between intra-, peri-, and postoperative complications. Overall, the rate of complications is 0-7%. Intraoperative complications include incomplete morcellation (2.3%), capsular perforation (2.2%), bladder (2.4%), and ureteric orifice (0.4%) injuries. Perioperative complications include postoperative urinary retention (0.2%), hematuria and clot retention (2.6%), and cystoscopy for clot evacuation (0.7%). Postoperative complications include dysuria (7.5%), stress (4.0%), urge (1.8%), transient (7%) and permanent (1.3%) urinary incontinence, urethral stricture (2%) and bladder neck contracture (1%). CONCLUSIONS: HoLEP is a safe procedure, with a satisfactory low complication rate. The most common reported perioperative complications are not severe (Clavien-Dindo classification grades 1-2). Further randomized studies are certainly warranted to fully determine the predictor of surgical complications in order to prevent them and improve this technique.

The Role of [18F]Fluciclovine PET/CT in the Characterization of High-Risk Primary Prostate Cancer: Comparison with [11C]Choline PET/CT and Histopathological Analysis.

The primary aim of the study was to evaluate the role of [18F]Fluciclovine PET/CT in the characterization of intra-prostatic lesions in high-risk primary PCa patients eligible for radical prostatectomy, in comparison with conventional [11C]Choline PET/CT and validated by prostatectomy pathologic examination. Secondary aims were to determine the performance of PET semi-quantitative parameters (SUVmax; target-to-background ratios [TBRs], using abdominal aorta, bone marrow and liver as backgrounds) for malignant lesion detection (and best cut-off values) and to search predictive factors of malignancy. A six sextants prostate template was created and used by PET readers and pathologists for data comparison and validation. PET visual and semi-quantitative analyses were performed: for instance, patient-based, blinded to histopathology; subsequently lesion-based, un-blinded, according to the pathology reference template. Among 19 patients included (mean age 63 years, 89% high and 11% very-high-risk, mean PSA 9.15 ng/mL), 45 malignant and 31 benign lesions were found and 19 healthy areas were selected (n = 95). For both tracers, the location of the "blinded" prostate SUVmax matched with the lobe of the lesion with the highest pGS in 17/19 cases (89%). There was direct correlation between [18F]Fluciclovine uptake values and pISUP. Overall, lesion-based (n = 95), the performance of PET semiquantitative parameters, with either [18F]Fluciclovine or [11C]Choline, in detecting either malignant/ISUP2-5/ISUP4-5 PCa lesions, was moderate and similar (AUCs ≥ 0.70) but still inadequate (AUCs ≤ 0.81) as a standalone staging procedure. A [18F]Fluciclovine TBR-L3 ≥ 1.5 would depict a clinical significant lesion with a sensitivity and specificity of 85% and 68% respectively; whereas a SUVmax cut-off value of 4 would be able to identify a ISUP 4-5 lesion in all cases (sensitivity 100%), although with low specificity (52%). TBRs (especially with threshold significantly higher than aorta and slightly higher than bone marrow), may be complementary to implement malignancy targeting.

Holmium laser prostatectomy in a tertiary Italian center: A prospective cost analysis in comparison with bipolar TURP and open prostatectomy.

OBJECTIVE: To assess the economic impact of Holmium laser enucleation of prostate (HoLEP) in comparison with transurethral resection of prostate (TURP) and open prostatectomy (OP). METHODS: Between January 2017 and January 2018, we prospectively enrolled 151 men who underwent HoLEP, TURP or OP at tertiary Italian center, due to bladder outflow obstruction symptoms. Patients with prostate volume ≤ 70 cc and those with prostate volume > 70 cc were scheduled for TURP or HoLEP and OP or HoLEP, respectively. Intraoperative and early post-operative functional outcomes were recorded up to 6 months follow up. Cost analysis was carried out considering direct costs (operating room [OR] utilization costs, nurse, surgeons and anesthesiologists' costs, OR disposable products costs and OR products sterilization costs), indirect costs (hospital stay costs and diagnostics costs) and global costs as sum of both direct and indirect plus general costs related to hospitalization. Cost analysis was performed comparing patients referred to TURP and HoLEP with prostate volume ≤ 70 cc and men underwent OP and HoLEP with prostate volume > 70 cc respectively. RESULTS: Overall, 53 (35.1%), 51 (33.7%) and 47 (31.1%) were scheduled to HoLEP, TURP and OP, respectively. Both TURP, HoLEP and OP proved to effectively improve urinary symptoms related to BPE. Considering patients with prostate volume ≤ 70 cc, median global cost of HoLEP was similar to median global cost of TURP (2151.69 € vs. 2185.61 €, respectively; p = 0.61). Considering patients with prostate volume > 70 cc, median global cost of HoLEP was found to be significantly lower than median global cost of OP (2174.15 € vs. 4064.97 €, respectively; p ≤ 0.001). CONCLUSIONS: Global costs of HoLEP are comparable to those of TURP, offering a cost saving of only 11.4 € in favor of HoLEP. Conversely, HoLEP proved to be a strong competitor of OP because of significant global cost sparing amounting to 1890.82 € in favor of HoLEP.

Prediction nomogram for 68Ga-PSMA-11 PET/CT in different clinical settings of PSA failure after radical treatment for prostate cancer.

OBJECTIVE: The objective of this study was to develop a clinical nomogram to predict gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA-11-PET/CT) positivity in different clinical settings of PSA failure. MATERIALS AND METHODS: Seven hundred three (n = 703) prostate cancer (PCa) patients with confirmed PSA failure after radical therapy were enrolled. Patients were stratified according to different clinical settings (first-time biochemical recurrence [BCR]: group 1; BCR after salvage therapy: group 2; biochemical persistence after radical prostatectomy [BCP]: group 3; advanced-stage PCa before second-line systemic therapies: group 4). First, we assessed 68Ga-PSMA-11-PET/CT positivity rate. Second, multivariable logistic regression analyses were used to determine predictors of positive scan. Third, regression-based coefficients were used to develop a nomogram predicting positive 68Ga-PSMA-11-PET/CT result and 200 bootstrap resamples were used for internal validation. Fourth, receiver operating characteristic (ROC) analysis was used to identify the most informative nomogram's derived cutoff. Decision curve analysis (DCA) was implemented to quantify nomogram's clinical benefit. RESULTS: 68Ga-PSMA-11-PET/CT overall positivity rate was 51.2%, while it was 40.3% in group 1, 54% in group 2, 60.5% in group 3, and 86.9% in group 4 (p < 0.001). At multivariable analyses, ISUP grade, PSA, PSA doubling time, and clinical setting were independent predictors of a positive scan (all p ≤ 0.04). A nomogram based on covariates included in the multivariate model demonstrated a bootstrap-corrected accuracy of 82%. The nomogram-derived best cutoff value was 40%. In DCA, the nomogram revealed clinical net benefit of > 10%. CONCLUSIONS: This novel nomogram proved its good accuracy in predicting a positive scan, with values ≥ 40% providing the most informative cutoff in counselling patients to 68Ga-PSMA-11-PET/CT. This tool might be important as a guide to clinicians in the best use of PSMA-based PET imaging.

State of the art of PET/CT with 11-choline and 18F-fluorocholine in the diagnosis and follow-up of localized and locally advanced prostate cancer.

OBJECTIVE: To provide an updated state of the art about the role of positron emission tomography/computed tomography (PET/CT) with 11C-Choline and 18F-fluorocholine in the localized and locally advanced Prostate Cancer (PCa) in the staging and restaging setting. METHODS: We performed a non-systematic review of the literature based on a free-text search in the National Library of Medicine Database (MEDLINE) to select English-language published papers evaluating PET and PET/CT imaging with radiolabelled choline in initial diagnosis and in post-treatment phase in PCa patients. RESULTS: PET and PET/CT with 11C-choline and 18F-fluorocholine have been largely investigated as non-invasive diagnostic tools in PCa. Actually, the relatively high rate of false negative findings due to the small dimension of neoplastic lesions and the available spatial resolution of PET tracers limits the routine use of choline PET and PET/CT in staging setting; moreover, it cannot reliably replace the lymph node (LN) dissection for detecting LN involvement. On restaging setting, Choline PET/CT showed a higher accuracy than conventional imaging modalities, especially in the detection of LN and systemic metastases, while it is less accurate than magnetic resonance imaging in the detection of local relapse. CONCLUSION: In the Prostate Specific Antigen (PSA) era with a large number of localized disease, the diagnostic performance of choline PET and PET/CT lack of reliability in initial diagnosis of PCa. The major clinical role of choline PET/CT is the re-staging of patients with a biochemical relapse after radical treatment; the promising performance of choline PET/CT scan in patients with low levels of PSA could also lead the clinicians for to perform PET-guided adjuvant curative therapies or palliative treatments in patients already treated radically for PCa.

State of the PET/CT with 11-choline and 18F-fluorocholine in the diagnosis and follow-up of localized and locally advanced prostate / Estado del PET TAC con Colina 11C y Fluorocolina 18F en el diagnóstico y seguimiento del cáncer de próstata localizado y localmente avanzado

OBJECTIVE: To provide an updated state of the art about the role of positron emission tomography/ computed tomography (PET/CT) with 11C-Choline and 18F-fluorocholine in the localized and locally advanced Prostate Cancer (PCa) in the staging and restaging setting. METHODS: We performed a non-systematic review of the literature based on a free-text search in the National Library of Medicine Database (MEDLINE) to select English-language published papers evaluating PET and PET/CT imaging with radiolabelled choline in initial diagnosis and in post-treatment phase in PCa patients. RESULTS: PET and PET/CT with 11C-choline and 18F-fluorocholine have been largely investigated as non-invasive diagnostic tools in PCa. Actually, the relatively high rate of false negative findings due to the small dimension of neoplastic lesions and the available spatial resolution of PET tracers limits the routine use of choline PET and PET/CT in staging setting; moreover, it cannot reliably replace the lymph node (LN) dissection for detecting LN involvement. On restaging setting, Choline PET/CT showed a higher accuracy than conventional imaging modalities, especially in the detection of LN and systemic metastases, while it is less accurate than magnetic resonance imaging in the detection of local relapse. CONCLUSION: In the Prostate Specific Antigen (PSA) era with a large number of localized disease, the diagnostic performance of choline PET and PET/CT lack of reliability in initial diagnosis of PCa. The major clinical role of choline PET/CT is the re-staging of patients with a biochemical relapse after radical treatment; the promising performance of choline PET/CT scan in patients with low levels of PSA could also lead the clinicians for to perform PET-guided adjuvant curative therapies or palliative treatments in patients already treated radically for PCa

OBJETIVOS: Ofrecer una puesta al día de lo último sobre el papel de la tomografía por emisión de positrones/Tomografía axial computarizada (PET/TAC) con colina 11C y fluorocolina 18 F en el cáncer de próstata (CaP) localizado y localmente avanzado. MÉTODOS: Realizamos una revisión no sistemática de la literatura basada en una búsqueda de texto libre en la Base de Datos de la Biblioteca nacional de Medicina (MEDLINE) para seleccionar las publicaciones en lengua inglesa que evaluaban la PET y PET/TAC con colina radiomarcada en el diagnóstico inicial y en la fase posterior al tratamiento en pacientes con CaP. RESULTADOS: El PET y PET/TAC con colina 11C y fluorocolina 18F han sido ampliamente investigados como herramientas diagnósticas no invasivas en el CaP. Realmente, la relativamente alta tasa de hallazgos falsos negativos debido a la pequeña dimensión de las lesiones neoplásicas y la resolución espacial disponible para los marcadores PET limitan la utilización rutinaria de PET y PET/TAC en el estadiaje; además, no puede reemplazar de una forma fiable a la linfadenectomía para detectar la afectación de los ganglios linfáticos. En re-estadiaje, el PET/TAC colina mostró una precisión superior a las modalidades radiológicas convencionales, especialmente en la detección de ganglios linfáticos y metástasis sistémicas, mientras que es menos preciso que la resonancia magnética en la detección de la recidiva local. CONCLUSION: In the Prostate Specific Antigen (PSA) era with a large number of localized disease, the diagnostic performance of choline PET and PET/CT lack of reliability in initial diagnosis of PCa. The major clinical role of choline PET/CT is the re-staging of patients with a biochemical relapse after radical treatment; the promising performance of choline PET/CT scan in patients with low levels of PSA could also lead the clinicians for to perform PET-guided adjuvant curative therapies or palliative treatments in patients already treated radically for PCa

11C-choline PET/CT for restaging of bladder cancer.

AIM: The aim of this study was to evaluate of C-choline PET/CT in bladder cancer (BC) patients with suspected relapse after primary therapy. METHODS: Twenty-five BC patients with surgery (21 [84%]) or radiotherapy (4 [16%]) with curative intent had PET/CT for suspicion of relapse. Mean TNM was T2b N0 M0 (range, T1a N0 M0 to T4 N2 M0), whereas mean age was 71.3 years (range, 50-85 years). Nine (36%) of 25 were treated with adjuvant or salvage chemotherapy within 6 months before PET/CT. Positive findings were validated by histology or correlative imaging and/or clinical follow-up lasting at least 12 months. Age, TNM, histology, previous chemotherapy, and type of primary treatment were correlated with PET/CT positivity by univariate and multivariate binary logistic regression analysis. RESULTS: C-choline PET/CT was positive in 16 (64%) of 25. Six (37.5%) of 16 were positive in residual bladder/bladder bed, with 2 local false positive (FP) and 1 false negative (FN) on lymph nodes (LNs); 3 of 16 patients had PET-positive LNs with 1 FP; 1 of 16 patients showed distant metastases. Two (12.5%) of 16 had positive residual bladder/bladder bed and locoregional LNs; 1 (6.3%) of 16, residual bladder/bladder bed and bone; metastasis, 1 (6.3%) of 16 residual bladder/bladder bed and lung metastasis; 2 (12.5%) of 16, LN and distant metastasis. Five (56%) of 9 of PET negatives were FN in residual bladder/bladder bed. Eighteen (72%) of 25 were validated by histology, with 7 (18%) of 25 by correlative imaging and/or clinical follow-up. C-choline PET/CT was sensitive, specific, and accurate, with good positive and negative predictive values for local relapse of 66.7%, 84.6%, 76%, 80%, and 73.3% and 90%, 93.3%, 92%, 90%, and 93.3% for LNs and distant relapse, respectively. No FP or FN was detected for distant metastasis. None of the investigated factors were statistically significant. CONCLUSION: C-choline PET/CT is useful for restaging BC suspected of relapse, especially for the evaluation of LN or distant metastases.